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Li M, Yao M, Wang L, Liu Y, Ji D, Yang Y, Lu F. The Early On-treatment Stiffness Decline Attributed to the Improved Hepatic Inflammation in Fibrotic Chronic Hepatitis B. J Clin Gastroenterol 2025; 59:456-463. [PMID: 38990730 PMCID: PMC11974622 DOI: 10.1097/mcg.0000000000002032] [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: 12/27/2023] [Accepted: 05/05/2024] [Indexed: 07/13/2024]
Abstract
OBJECTIVES Hepatic inflammation, the driver of fibrosis progression in liver disease, can impact the accuracy of liver stiffness measurement (LSM). We wondered whether the decline in LSM value during the early antiviral phase was mainly attributed to the control of hepatic inflammation or the regression of fibrosis in patients with fibrotic/cirrhotic chronic hepatitis B (CHB). PATIENTS AND METHODS The study cohort was composed of 82 patients with CHB who underwent antiviral and antifibrotic therapy at the Fifth Medical Center of PLA General Hospital. All patients had liver biopsies at both baseline and 72 weeks posttherapy. Liver pathology and clinical data, including the LSM value, were collected. RESULTS After 72 weeks of treatment, both the histologic activity index score and fibrosis score, as well as the LSM value, were significantly decreased ( P < 0.001), compared with their baseline values. The pretreatment correlation of LSM value with either histologic activity index score ( r = 0.526 vs r = 0.286) or fibrosis score ( r = 0.677 vs r = 0.587) was attenuated at 72 weeks. Notably, logistic regression analysis revealed that the improvement in inflammation (odds ratio = 1.018, 95% CI: 1.002-1.031, P = 0.023) but not fibrosis (odds ratio = 0.994, 95% CI: 0.980-1.009, P = 0.414), had an impact on the change in LSM values between baseline and at 72-week treatment. CONCLUSIONS The findings of this study suggest that in patients with fibrotic CHB receiving antiviral medication, the early phase reduction in LSM value was related to improved hepatic inflammation rather than fibrosis regression.
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Affiliation(s)
- Mingwei Li
- Research Center for Clinical Medical Sciences, the Fourth Hospital of Shijiazhuang, Shijiazhuang, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Mingjie Yao
- Department of Anatomy and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Fujian Provincial Key Laboratory of Hepatic DrugResearch, Fuzhou, China
| | - Leijie Wang
- College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
| | - Yanna Liu
- Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Dong Ji
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Yongping Yang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Fengmin Lu
- Department of Microbiology and Infectious Disease Center, School of Basic Medicine, Peking University Health Science Center, Beijing, China
- Center of Precision Medicine, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
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Parlati L, Aubé C, Lewin M, Boursier J, Ronot M, Paisant A. SIAD (Societé d'Imagerie Abdominale et Digestive) and AFEF (Association Française pour l'Etude du Foie) best practice position paper on the implementation of ultrasound elastography in clinical practice. Diagn Interv Imaging 2025:S2211-5684(25)00070-1. [PMID: 40210513 DOI: 10.1016/j.diii.2025.03.010] [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: 03/11/2025] [Revised: 03/31/2025] [Accepted: 03/31/2025] [Indexed: 04/12/2025]
Abstract
PURPOSE The diagnosis of liver fibrosis is critical in managing chronic liver diseases. The EASL guidelines now recognize ultrasound elastography as a valuable, non-invasive method for assessing liver fibrosis. However, there is a lack of uniform use and reporting of the technique. The purpose of this position paper was to provide guidance on using ultrasound elastography techniques and interpreting results in clinical practice. MATERIALS AND METHODS A French national consensus panel of experts in radiology and hepatology, convened by SIAD (Société d'Imagerie Abdominale et Digestive) and AFEF (Association Française pour l'Etude du Foie), developed a position statement paper on best practices in ultrasound elastography. They were established using an online Delphi methodology that included an online panel discussion and item preparation. Consensus was achieved when ≥ 80 % of the participants agreed with a specific recommendation. RESULTS The accuracy and reliability of ultrasound elastography results could be significantly affected by a variety of operator-related and patient-related factors. Standard recommendations have been established in two areas, including recommendations for measurements and factors affecting results and reliability, and guidelines for standardized reporting of ultrasound elastography results. CONCLUSION This position paper is a comprehensive and accessible guide for clinicians that outlines best practices and standardized protocols to improve the reliability of ultrasound elastography assessments.
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Affiliation(s)
- Lucia Parlati
- Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris 75014, France; Department of Hepatology, Hôpital Cochin, AP-HP, Paris 75014, France.
| | - Christophe Aubé
- Laboratoire HIFIH, Université d'Angers, SFR ICAT 4208, Angers 49000, France; Department of Radiology, CHU Angers, Angers 49000, France
| | - Maïté Lewin
- Department of Radiology, Hôpital Paul Brousse, AP-HP, Villejuif 94804, France; Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre 94270, France
| | - Jérôme Boursier
- Laboratoire HIFIH, Université d'Angers, SFR ICAT 4208, Angers 49000, France; Department of Hepato-Gastroenterology and Digestive Oncology, CHU Angers, Angers 49000, France
| | - Maxime Ronot
- Department of Radiology, Hôpital Beaujon, AP-HP. Nord, Clichy 92118, France; Université Paris-Cité, UMR 1149, CRI, Paris 75018, France
| | - Anita Paisant
- Laboratoire HIFIH, Université d'Angers, SFR ICAT 4208, Angers 49000, France; Department of Radiology, CHU Angers, Angers 49000, France
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Sato S, Iino C, Sasada T, Soma G, Furusawa K, Yoshida K, Sawada K, Mikami T, Fukuda S, Nakaji S, Sakuraba H. An epidemiological study on the factors including genetic polymorphism influencing ALT >30 U/L and liver fibrosis progression in metabolic dysfunction-associated steatotic liver disease among the general population. JGH Open 2024; 8:e70043. [PMID: 39713746 PMCID: PMC11659511 DOI: 10.1002/jgh3.70043] [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: 06/19/2024] [Revised: 09/29/2024] [Accepted: 10/07/2024] [Indexed: 12/24/2024]
Abstract
Background and Aim Identifying the factors contributing to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), a lifestyle-related disease, is crucial for preventing future liver-related deaths. This study aimed to epidemiologically investigate factors, including single-nucleotide polymorphisms (SNPs) associated with alanine aminotransferase (ALT) levels >30 U/L and potential risk factors for liver fibrosis, in a general population cohort of patients with MASLD. Methods Among 1059 participants in the health checkup project, 228 who were diagnosed with MASLD were analyzed. Liver fat content and stiffness were measured using FibroScan, and 13 SNPs associated with non-alcoholic fatty liver disease (NAFLD) were measured in addition to other clinical parameters. Results In the multivariate analysis, male sex, younger age, and high triglyceride levels were significant risk factors for ALT levels >30 U/L (P-value < 0.05). Furthermore, among the 13 SNPs measured, only the GG genotypes of patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 and rs2896019 were significant risk factors for ALT levels >30 U/L (P-value 0.004 and 0.007). The GG genotypes of PNPLA3 rs738409 and rs2896019 had higher FibroScan-aspartate aminotransferase (FAST) and APRI scores than the CC + CG and TT + TG genotypes (P-value < 0.05). In addition, multivariate analysis revealed that the GG genotypes of rs738409 and rs2896019 were significant risk factors independent of cardiovascular metabolic risk for patients with MASLD (P-value 0.038 and 0.021). Conclusion An individualized treatment approach is warranted for patients with MASLD due to the influence of various factors on its progression, including genetic factors and lifestyle diseases.
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Affiliation(s)
- Satoshi Sato
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
| | - Chikara Iino
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
| | - Takafumi Sasada
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
| | - Go Soma
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
| | - Keisuke Furusawa
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
| | - Kenta Yoshida
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
| | - Kaori Sawada
- Department of Preemptive MedicineHirosaki University Graduate School of MedicineHirosakiJapan
| | - Tatsuya Mikami
- Department of Preemptive MedicineHirosaki University Graduate School of MedicineHirosakiJapan
| | - Shinsaku Fukuda
- Department of Preemptive MedicineHirosaki University Graduate School of MedicineHirosakiJapan
| | - Shigeyuki Nakaji
- Department of Preemptive MedicineHirosaki University Graduate School of MedicineHirosakiJapan
| | - Hirotake Sakuraba
- Department of Gastroenterology, Hematology and Clinical ImmunologyHirosaki University Graduate School of MedicineHirosakiJapan
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Kim MN. [Noninvasive Imaging Test to Assess Liver Fibrosis: Vibration-controlled Transient Elastography]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:201-205. [PMID: 39582307 DOI: 10.4166/kjg.2024.120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 10/31/2024] [Accepted: 11/04/2024] [Indexed: 11/26/2024]
Abstract
Liver fibrosis refers to the formation of scar tissue in the liver when inflammation persists over a long period. Assessing liver fibrosis is crucial for predicting the prognosis of chronic liver disease and managing patients with these conditions. Although a liver biopsy remains the gold standard for assessing liver fibrosis, it is limited by its invasive nature. Consequently, continuous efforts have been made to develop non-invasive methods for evaluating liver fibrosis, including imaging techniques and serum biomarkers. Vibration-controlled transient elastography (VCTE), a representative non-invasive imaging technique, has been used widely for liver fibrosis assessment since its introduction in 2003. This paper discusses the principles and methods of measurement, the advantages and disadvantages, and the considerations for interpreting VCTE based on the 2024 KASL Clinical Practice Guidelines for Non-invasive Tests to Assess Liver Fibrosis in Chronic Liver Disease. In addition, the diagnostic utility of VCTE in chronic viral hepatitis is reviewed.
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Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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5
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Selicean SE, Felli E, Wang C, Nulan Y, Lozano JJ, Guixé-Muntet S, Ștefănescu H, Bosch J, Berzigotti A, Gracia-Sancho J. Stiffness-induced modulation of ERG transcription factor in chronic liver disease. NPJ GUT AND LIVER 2024; 1:7. [PMID: 39381160 PMCID: PMC11459910 DOI: 10.1038/s44355-024-00007-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 07/19/2024] [Indexed: 10/10/2024]
Abstract
Chronic liver disease (CLD) is characterised by liver sinusoidal endothelial cells (LSECs) dysfunction. Mechanical forces and inflammation are among the leading factors. ETS-related gene (ERG) is an endothelial-specific transcription factor, involved in maintaining cell quiescence and homeostasis. Our study aimed to understand the expression and modulation of ERG in CLD. ERG expression was characterised and correlated to clinical data in human liver cirrhosis at different disease stages. ERG dynamics in response to stiffness and inflammation were investigated in primary healthy and cirrhotic rat LSEC and in human umbilical vein endothelial cells (HUVECs). ERG is markedly downregulated in cirrhosis independently of disease stage or aetiology and its expression is modulated by substrate stiffness in ECs. Inflammation downregulates ERG in cells on physiological stiffness, but not on high stiffness, suggesting a complementary role of inflammation and stiffness in suppressing ERG. This study outlines ERG as an LSEC inflammation and stiffness-responsive transcription factor in cirrhosis.
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Affiliation(s)
- Sonia-Emilia Selicean
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
| | - Eric Felli
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
| | - Cong Wang
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
| | - Yeldos Nulan
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
| | - Juan José Lozano
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Sergi Guixé-Muntet
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Horia Ștefănescu
- Liver Unit, Regional Institute of Gastroenterology and Hepatology Octavian Fodor, Cluj-Napoca, Romania
| | - Jaime Bosch
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
| | - Jordi Gracia-Sancho
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, University of Barcelona, Barcelona, Spain
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU. KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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Roulot D, Brichler S, Layese R, D'alteroche L, Ganne-Carrie N, Stern C, Saviano A, Leroy V, Roudot-Thoraval F, De Ledinghen V. High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00776-6. [PMID: 39209196 DOI: 10.1016/j.cgh.2024.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 07/17/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND & AIMS Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here, we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. METHODS A total of 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSMs) using Fibroscan, within a period of 6 months maximum, were investigated retrospectively. Area under the receiver operating characteristic curve and Youden index were used to establish cutoff values of LSM. TE was compared with other noninvasive tests: aspartate aminotransferase to platelet ratio index, Fibrosis-4, and Delta-4 fibrosis scores. RESULTS Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3; and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with an Area under the receiver operating characteristic curve of 0.88 and 0.86, which were significantly higher than those obtained with the other noninvasive tests (P = .004 and P < .001). With a cutoff value of >12 kPa for cirrhosis, the sensitivity was 70.5%, specificity was 86.2%, positive predictive value was 72.4%, negative predictive value was 85.1%, and accuracy was 80.9%. Using 10.4 kPa as the cutoff value for F3, the sensitivity was 70.2%, specificity was 83.5%, positive predictive value was 82.5%, negative predictive value was 71.7%, and accuracy was 76.5%. In 89% of patients with LSM ≤6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis. CONCLUSION TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in patients with CHD. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values <6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.
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Affiliation(s)
- Dominique Roulot
- AP-HP, Hôpital Avicenne, Unité d'Hépatologie, Bobigny; Université Sorbonne Paris Nord, Bobigny; Inserm U955, Equipe 18, Université Paris-Est, Créteil, France.
| | - Ségolène Brichler
- AP-HP, Hôpital Avicenne, Laboratoire de Microbiologie Clinique; Université Sorbonne Paris Nord, Centre National de Référence des Hépatites B, C et Delta, Bobigny, Inserm U955, Equipe 18, Université Paris-Est, Créteil, France
| | - Richard Layese
- Université Paris-Est Créteil, INSERM, IMRB, CEpiA (Clinical Epidemiology and Ageing Unit) Team, Créteil; AP-HP, Hôpital Henri-Mondor, Unité de Recherche Clinique (URC Mondor), Créteil, France
| | | | - Nathalie Ganne-Carrie
- AP-HP, Hôpital Avicenne, Service d'Hépatologie, Bobigny; Université Sorbonne Paris Nord, Bobigny; INSERM U1138, Université de Paris, France
| | | | - Antonio Saviano
- Pôle Hépato-digestif, University Hospital, Strasbourg; Inserm U110, Strasbourg, France
| | - Vincent Leroy
- AP-HP, Hôpital Henri-Mondor, Service d'Hépatologie, Créteil; Inserm U955, Equipe 18, Université Paris-Est, Créteil, France
| | - Françoise Roudot-Thoraval
- Université Paris-Est Créteil, INSERM, IMRB, CEpiA (Clinical Epidemiology and Ageing Unit) Team, Créteil; AP-HP, Hôpital Henri-Mondor, Unité de Recherche Clinique (URC Mondor), Créteil, France
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Arteel GE. Hepatic Extracellular Matrix and Its Role in the Regulation of Liver Phenotype. Semin Liver Dis 2024; 44:343-355. [PMID: 39191427 DOI: 10.1055/a-2404-7973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/29/2024]
Abstract
The hepatic extracellular matrix (ECM) is most accurately depicted as a dynamic compartment that comprises a diverse range of players that work bidirectionally with hepatic cells to regulate overall homeostasis. Although the classic meaning of the ECM referred to only proteins directly involved in generating the ECM structure, such as collagens, proteoglycans, and glycoproteins, the definition of the ECM is now broader and includes all components associated with this compartment. The ECM is critical in mediating phenotype at the cellular, organ, and even organismal levels. The purpose of this review is to summarize the prevailing mechanisms by which ECM mediates hepatic phenotype and discuss the potential or established role of this compartment in the response to hepatic injury in the context of steatotic liver disease.
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Affiliation(s)
- Gavin E Arteel
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
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Thakral N, Desalegn H, Diaz LA, Cabrera D, Loomba R, Arrese M, Arab JP. A Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD. Semin Liver Dis 2024; 44:273-286. [PMID: 38991536 DOI: 10.1055/a-2364-2928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
The new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity of what was historically referred to as nonalcoholic fatty liver disease. The heterogeneity within this spectrum is influenced by several factors which include but are not limited to demographic/dietary factors, the amount of alcohol use and drinking patterns, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The net effect of this dynamic and intricate system-level interaction is reflected in the phenotypic presentation of MASLD. Therefore, the application of precision medicine in this scenario aims at complex phenotyping with consequent individual risk prediction, development of individualized preventive strategies, and improvements in the clinical trial designs. In this review, we aim to highlight the importance of precision medicine approaches in MASLD, including the use of novel biomarkers of disease, and its subsequent utilization in future study designs.
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Affiliation(s)
- Nimish Thakral
- Division of Gastroenterology and Hepatology, University of Kentucky, Lexington, Kentucky
| | - Hailemichael Desalegn
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Luis Antonio Diaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Daniel Cabrera
- Centro de Investigación e Innovación Biomédica (CiiB), Universidad de los Andes, Santiago, Chile
- Escuela de Medicina, Facultad de Ciencias Medicas, Universidad Bernardo O'Higgins, Santiago, Chile
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology, MASLD Research Center, University of California San Diego, San Diego, California
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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10
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Deep A, Kumari S, Malakar S, Swaroop S, Rungta S. Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India. Cureus 2024; 16:e64550. [PMID: 39144860 PMCID: PMC11322852 DOI: 10.7759/cureus.64550] [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] [Accepted: 07/15/2024] [Indexed: 08/16/2024] Open
Abstract
Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% females and 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereas in the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01). Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However, compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higher bilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift toward prevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHC who are obese and have low platelet counts with higher liver enzymes.
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Affiliation(s)
- Amar Deep
- Medical Gastroenterology, King George's Medical University, Lucknow, IND
| | - Shweta Kumari
- Biochemistry, King George's Medical University, Lucknow, IND
| | - Sayan Malakar
- Medical Gastroenterology, King George's Medical University, Lucknow, IND
| | | | - Sumit Rungta
- Medical Gastroenterology, King George's Medical University, Lucknow, IND
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11
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Rajendran J, Irrinki S, Gupta V, Singh V, Sinha SK, Lal A, Kurdia K, Das A, Yadav TD. Elastography for Evaluation of Regression in Liver Fibrosis After Surgical Biliary Drainage for Benign Biliary Strictures: A Practical Possibility? J Clin Gastroenterol 2024; 58:502-506. [PMID: 37725412 DOI: 10.1097/mcg.0000000000001895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 06/25/2023] [Indexed: 09/21/2023]
Abstract
BACKGROUND Hepatic fibrosis and secondary biliary cirrhosis are consequences of long-standing benign biliary strictures. Evidence on the reversibility of fibrosis after the repair is incongruous. METHODOLOGY A prospective observational study on patients who underwent Roux-en-Y hepaticojejunostomy for benign biliary stricture. A liver biopsy was performed during repair and correlated with preoperative elastography. The improvement in liver functions and regression of fibrosis was compared with preoperative liver function tests and elastography. RESULTS A Total of 47 patients [mean age-38.9 y (Range: 21 to 66)] with iatrogenic benign biliary stricture were included. A strong female preponderance was noted. High strictures (type III and IV) comprised 72.7% of the study group. The median interval (injury to repair) was 7 months (2 to 72 mo). The median duration of jaundice was 3 months (1 to 20 mo). Both factors had a significant correlation with the stage of fibrosis ( P =0.001 and P =0.03, respectively). Liver biopsy revealed stage I, II, III, and IV fibrosis in 26 (55.3%), 11 (23.4%), 2 (4.3%), and 2(4.3%), respectively. The remaining 6 (12.8%) had no fibrosis. The severity of fibrosis had a good correlation with preoperative liver stiffness measurement-value on FibroScan. Significant improvement in liver function tests (bilirubin-3.55±3.48 vs. 0.59±0.52; Albumin-3.85±0.61 vs. 4.14±0.37; ALP-507.66±300.65 vs. 167±132.07; P value 0.00) and regression of fibrosis (liver stiffness measurement; 10.42±5.91 vs. 5.85±3.01, P value 0.00) was observed after repair of the strictures. CONCLUSION Improved biliary function and regression of liver fibrosis can be achieved with timely repair of benign biliary stricture and it is feasible to be evaluated using elastography.
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Affiliation(s)
| | | | | | | | | | | | | | - Ashim Das
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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12
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Buti M, Palom A, Riveiro-Barciela M. Editorial: Liver elastography for chronic hepatitis D-the end of liver biopsy? Aliment Pharmacol Ther 2024; 59:898-899. [PMID: 38462685 DOI: 10.1111/apt.17890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
LINKED CONTENTThis article is linked to Sandmann et al paper. To view this article, visit https://doi.org/10.1111/apt.17878
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Affiliation(s)
- María Buti
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Barcelona, Spain
| | - Adriana Palom
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Barcelona, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
- CIBERehd, Instituto Carlos III, Barcelona, Spain
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13
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Fan R, Li G, Yu N, Chang X, Arshad T, Liu WY, Chen Y, Wong GLH, Jiang Y, Liang X, Chen Y, Jin XZ, Dong Z, Leung HHW, Wang XD, Zeng Z, Yip TCF, Xie Q, Tan D, You S, Ji D, Zhao J, Sanyal AJ, Sun J, Zheng MH, Wong VWS, Yang Y, Hou J. aMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients. Clin Gastroenterol Hepatol 2023; 21:3070-3079.e13. [PMID: 36933605 DOI: 10.1016/j.cgh.2023.03.005] [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: 11/08/2022] [Revised: 02/07/2023] [Accepted: 03/07/2023] [Indexed: 03/20/2023]
Abstract
BACKGROUND & AIMS The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. METHODS A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. RESULTS In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). CONCLUSIONS The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.
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Affiliation(s)
- Rong Fan
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Guanlin Li
- Medical Data Analytics 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
| | - Ning Yu
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiujuan Chang
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Tamoore Arshad
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Wen-Yue Liu
- Department of Endocrinology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yan Chen
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Grace Lai-Hung Wong
- Medical Data Analytics 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
| | - Yiyue Jiang
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xieer Liang
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongpeng Chen
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao-Zhi Jin
- Nonalcoholic Fatty Liver Disease Research Center, Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zheng Dong
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Howard Ho-Wai Leung
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiao-Dong Wang
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Zhen Zeng
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Terry Cheuk-Fung Yip
- Medical Data Analytics 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
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Deming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Shaoli You
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Dong Ji
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jun Zhao
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Arun J Sanyal
- Division of Gastroenterology, Virginia Commonwealth University, Richmond, Virginia
| | - Jian Sun
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ming-Hua Zheng
- Nonalcoholic Fatty Liver Disease Research Center, Department of Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytics 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.
| | - Yongping Yang
- Senior Department of Hepatology, Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Jinlin Hou
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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14
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Aspromonte N, Fumarulo I, Petrucci L, Biferali B, Liguori A, Gasbarrini A, Massetti M, Miele L. The Liver in Heart Failure: From Biomarkers to Clinical Risk. Int J Mol Sci 2023; 24:15665. [PMID: 37958649 PMCID: PMC10649397 DOI: 10.3390/ijms242115665] [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: 09/20/2023] [Revised: 10/24/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
Heart failure (HF) is a clinical syndrome due to heart dysfunction, but in which other organs are also involved, resulting in a complex multisystemic disease, burdened with high mortality and morbidity. This article focuses on the mutual relationship between the heart and liver in HF patients. Any cause of right heart failure can cause hepatic congestion, with important prognostic significance. We have analyzed the pathophysiology underlying this double interaction. Moreover, we have explored several biomarkers and non-invasive tests (i.e., liver stiffness measurement, LSM) potentially able to provide important support in the management of this complex disease. Cardiac biomarkers have been studied extensively in cardiology as a non-invasive diagnostic and monitoring tool for HF. However, their usefulness in assessing liver congestion in HF patients is still being researched. On the other hand, several prognostic scores based on liver biomarkers in patients with HF have been proposed in recent years, recognizing the important burden that liver involvement has in HF. We also discuss the usefulness of a liver stiffness measurement (LSM), which has been recently proposed as a reliable and non-invasive method for assessing liver congestion in HF patients, with therapeutic and prognostic intentions. Lastly, the relationship between LSM and biomarkers of liver congestion is not clearly defined; more research is necessary to establish the clinical value of biomarkers in assessing liver congestion in HF patients and their relationship with LSM.
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Affiliation(s)
- Nadia Aspromonte
- Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy; (I.F.); (M.M.)
- Department of Cardiovascular and Thoracic Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Isabella Fumarulo
- Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy; (I.F.); (M.M.)
- Department of Cardiovascular and Thoracic Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Lucrezia Petrucci
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy; (L.P.); (B.B.); (A.L.); (A.G.); (L.M.)
- Department of Medical and Surgical Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Bianca Biferali
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy; (L.P.); (B.B.); (A.L.); (A.G.); (L.M.)
- Department of Medical and Surgical Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Antonio Liguori
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy; (L.P.); (B.B.); (A.L.); (A.G.); (L.M.)
- Department of Medical and Surgical Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy; (L.P.); (B.B.); (A.L.); (A.G.); (L.M.)
- Department of Medical and Surgical Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Massimo Massetti
- Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy; (I.F.); (M.M.)
- Department of Cardiovascular and Thoracic Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
| | - Luca Miele
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy; (L.P.); (B.B.); (A.L.); (A.G.); (L.M.)
- Department of Medical and Surgical Sciences, A. Gemelli University Policlinic Foundation IRCCS, 00168 Rome, Italy
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15
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Chen H, Shen Y, Wu SD, Zhu Q, Weng CZ, Zhang J, Wang MX, Jiang W. Diagnostic role of transient elastography in patients with autoimmune liver diseases: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:5503-5525. [PMID: 37900994 PMCID: PMC10600811 DOI: 10.3748/wjg.v29.i39.5503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 09/09/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023] Open
Abstract
BACKGROUND Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying. AIM To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD. METHODS The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis. RESULTS A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80. CONCLUSION Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.
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Affiliation(s)
- Hong Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Yue Shen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Sheng-Di Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Qin Zhu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
| | - Cheng-Zhao Weng
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
| | - Jun Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
| | - Mei-Xia Wang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
| | - Wei Jiang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, Fujian Province, China
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
- Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
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16
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Chouari T, Merali N, La Costa F, Santol J, Chapman S, Horton A, Aroori S, Connell J, Rockall TA, Mole D, Starlinger P, Welsh F, Rees M, Frampton AE. The Role of the Multiparametric MRI LiverMultiScan TM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis. Cancers (Basel) 2023; 15:4863. [PMID: 37835557 PMCID: PMC10571783 DOI: 10.3390/cancers15194863] [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: 04/11/2023] [Revised: 08/05/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.
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Affiliation(s)
- Tarak Chouari
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Nabeel Merali
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Francesca La Costa
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Jonas Santol
- Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, 1090 Vienna, Austria
- Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
| | - Shelley Chapman
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Alex Horton
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Somaiah Aroori
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery and Transplant Surgery, Derriford Hospital, Plymouth PL6 8DH, UK
| | | | - Timothy A. Rockall
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Damian Mole
- Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH10 5HF, UK
- Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH105HF, UK
| | - Patrick Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN 55902, USA
- Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
- Department of Surgery, Medical University of Vienna, General Hospital, 1090 Vienna, Austria
| | - Fenella Welsh
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Myrddin Rees
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Adam E. Frampton
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
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17
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Masaoka R, Gyotoku Y, Shirahashi R, Suda T, Tamano M. Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance. World J Clin Cases 2023; 11:5204-5214. [PMID: 37621583 PMCID: PMC10445062 DOI: 10.12998/wjcc.v11.i22.5204] [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: 05/10/2023] [Revised: 06/23/2023] [Accepted: 07/07/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND The treatment of hepatitis C with direct-acting antiviral agents (DAAs) produces a high rate of sustained virological response (SVR) with fewer adverse events than interferon (IFN) therapy with a similar effect in inhibiting carcinogenesis as IFN therapy. The age-male-albumin-bilirubin-platelets (aMAP) score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients, and the velocity of shear waves (Vs) measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk. Combining these two may improve the prediction of carcinogenic risk. AIM To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients. METHODS This retrospective, observational study involved hepatitis C patients treated with DAAs who achieved SVR. Vs was measured before treatment (baseline), at the end of treatment (EOT), and 12 wk (follow-up 12) and 24 wk (follow-up 24) after treatment. The patients were followed for at least six months after EOT to determine whether cancer developed. Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis. The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic (ROC) curve analyses. RESULTS A total of 279 patients (mean age 65.9 years, 118 males, 161 females) were included in the analysis. Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase, platelets, α-fetoprotein, Vs, and the Fib-4 index as explanatory variables; only Vs was found to be significant (P = 0.0296). The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s. Carcinoma developed in 2.0% (3/151) of those with Vs < 1.53 m/s and in 10.5% (9/86) of those with Vs ≥ 1.53 m/s. CONCLUSION In hepatitis C patients after SVR, combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.
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Affiliation(s)
- Rion Masaoka
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Yoshinori Gyotoku
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Ryosaku Shirahashi
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Toshikuni Suda
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Masaya Tamano
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
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18
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Brunetto MR, Ricco G, Negro F, Wedemeyer H, Yurdaydin C, Asselah T, Papatheodoridis G, Gheorghe L, Agarwal K, Farci P, Buti M. EASL Clinical Practice Guidelines on hepatitis delta virus. J Hepatol 2023; 79:433-460. [PMID: 37364791 DOI: 10.1016/j.jhep.2023.05.001] [Citation(s) in RCA: 105] [Impact Index Per Article: 52.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 06/28/2023]
Abstract
Hepatitis D virus (HDV) is a defective virus that requires the hepatitis B virus to complete its life cycle and cause liver damage in humans. HDV is responsible for rare acute and chronic liver diseases and is considered the most aggressive hepatitis virus. Acute infection can cause acute liver failure, while persistent infection typically causes a severe form of chronic hepatitis which is associated with rapid and frequent progression to cirrhosis and its end-stage complications, hepatic decompensation and hepatocellular carcinoma. Major diagnostic and therapeutic innovations prompted the EASL Governing Board to commission specific Clinical Practice Guidelines on the identification, virologic and clinical characterisation, prognostic assessment, and appropriate clinical and therapeutic management of HDV-infected individuals.
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Gardner AR, Ma Y, Bacchetti P, Price JC, Kuniholm MH, French AL, Gange S, Adimora AA, Minkoff H, Kassaye S, Ofotokun I, Rosenberg W, Kovacs AAZ, Tien PC. Longitudinal Assessment of the Enhanced Liver Fibrosis Score in the Era of Contemporary HIV and Hepatitis C Virus Treatment. J Infect Dis 2023; 227:1274-1281. [PMID: 35951669 PMCID: PMC10226657 DOI: 10.1093/infdis/jiac315] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/25/2022] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND The trajectory of liver fibrosis is not well understood in the contemporary era of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) therapy. METHODS We assessed the Enhanced Liver Fibrosis (ELF) score, aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) in 116 women with HIV/HCV coinfection over a 4-year period. Random-effects linear regression models examined the rate of fibrosis change 1-2 years before starting HCV treatment, within 1 year before starting (peri-HCV treatment), within 1 year after and 1-2 years post-HCV treatment in unadjusted and adjusted models including age, race, and changes from pretreatment of factors that might affect fibrosis (eg, alcohol, integrase strand inhibitor [INSTI] use, waist circumference, CD4 count). RESULTS INSTI use nearly doubled from pre- to peri-HCV treatment. In unadjusted analysis, there was a 3.3% rate of rise in ELF pre-HCV treatment, 2.2% and 3.6% rate of decline during the peri- and 1-year post-HCV treatment period, respectively, followed by a 0.3% rise. Similar findings were observed for APRI and FIB-4. There was little effect on the estimated fibrosis trajectories after adjustment. CONCLUSIONS The apparent lack of decline in biomarkers of liver fibrosis beyond 1 year after HCV cure suggests that continued monitoring of liver fibrosis and interventions to mitigate progression in people with HIV after HCV cure remains essential.
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Affiliation(s)
| | - Yifei Ma
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Peter Bacchetti
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Jennifer C Price
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Mark H Kuniholm
- Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York, USA
| | - Audrey L French
- Department of Medicine, Stroger Hospital, Cook County Health, Chicago, Illinois, USA
| | - Stephen Gange
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Adaora A Adimora
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Howard Minkoff
- Department of Obstetrics and Gynecology, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA
| | - Seble Kassaye
- Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Igho Ofotokun
- Department of Medicine, Emory University, Atlanta, Georgia, USA
| | - William Rosenberg
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom
| | - Andrea A Z Kovacs
- Department of Pediatrics, University of Southern California, Los Angeles, California, USA
| | - Phyllis C Tien
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
- Infectious Disease Section, Department of Veterans Affairs Medical Center, San Francisco, California, USA
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20
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Majumdar I, Talal AH, Harmon CM, Tabaczynsk E, Cercone K, Wrotniak BH, Mastrandrea LD, Quattrin T. Role of Dual-Contingency Management in Family-Based Obesity Therapy and the Effects of Weight Loss on Liver Transient Elastography Parameters in Youth: A Pilot Study. Cureus 2023; 15:e36629. [PMID: 37155438 PMCID: PMC10122838 DOI: 10.7759/cureus.36629] [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] [Accepted: 03/23/2023] [Indexed: 05/10/2023] Open
Abstract
The pilot study evaluated contingency management (CM) for family-based obesity therapy (FBT). The secondary outcome assessed the association of the hepatic transient electrography (TE) parameters, including the controlled attenuation parameter (CAP) and liver stiffness (LSM), and changes in liver function blood tests and BMI changes in youth involved in intensive FBT. It included youth-parent dyads from an urban pediatric center randomized to weekly behavioral therapy (BT, n= 4) who received fixed financial compensation for attendance, or BT+CM (n= 5) who received an escalating monetary reward for weight loss. At week 30, all youth and parents had weight-loss trends without significant differences between groups. While the TE measures and blood tests were normal in the youth at baseline and week 30, the CAP changes correlated with BMI changes (R2= 0.86, P< 0.001) and LSM changes with alanine aminotransferase changes (R2= 0.79, P=0.005). In conclusion, BT+CM did not significantly add to the BMI improvement seen with BT alone in youth and their parents. However, in youth with obesity and normal liver blood tests, TE may be useful for monitoring changes in fatty liver disease.
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Affiliation(s)
- Indrajit Majumdar
- Pediatric Endocrinology, Mount Sinai Medical Center, New York, USA
- Pediatric Endocrinology, Valley Medical Group, Paramus, USA
| | - Andrew H Talal
- Medicine, Division of Gastroenterology, Hepatology and Nutrition, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, USA
| | - Carrol M Harmon
- Surgery, Pediatric Surgery, John R Oishei Children's Hospital/Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, USA
| | - Emily Tabaczynsk
- Pediatrics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
| | - Kristen Cercone
- Psychiatry, John R. Oishei Children's Hospital/Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, USA
| | - Brian H Wrotniak
- Pediatrics, John R. Oishei Children's Hospital/UBMD Pediatrics, Buffalo, USA
| | - Lucy D Mastrandrea
- Pediatrics, Division of Pediatric Endocrinology and Diabetes, John R. Oishei Children's Hospital/Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, USA
| | - Teresa Quattrin
- Pediatrics, Division of Pediatric Endocrinology and Diabetes, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, USA
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Taru MG, Neamti L, Taru V, Procopciuc LM, Procopet B, Lupsor-Platon M. How to Identify Advanced Fibrosis in Adult Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) Using Ultrasound Elastography-A Review of the Literature and Proposed Multistep Approach. Diagnostics (Basel) 2023; 13:diagnostics13040788. [PMID: 36832276 PMCID: PMC9955630 DOI: 10.3390/diagnostics13040788] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/15/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), and its progressive form, non-alcoholic steatohepatitis (NASH), represent, nowadays, real challenges for the healthcare system. Liver fibrosis is the most important prognostic factor for NAFLD, and advanced fibrosis is associated with higher liver-related mortality rates. Therefore, the key issues in NAFLD are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. We critically reviewed the ultrasound (US) elastography techniques for the quantitative characterization of fibrosis, steatosis, and inflammation in NAFLD and NASH, with a specific focus on how to differentiate advanced fibrosis in adult patients. Vibration-controlled transient elastography (VCTE) is still the most utilized and validated elastography method for liver fibrosis assessment. The recently developed point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) techniques that use multiparametric approaches could bring essential improvements to diagnosis and risk stratification.
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Affiliation(s)
- Madalina-Gabriela Taru
- Hepatology Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Lidia Neamti
- Hepatology Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Vlad Taru
- Hepatology Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria
- Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, 1090 Vienna, Austria
| | - Lucia Maria Procopciuc
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Bogdan Procopet
- Hepatology Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Monica Lupsor-Platon
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania
- Correspondence:
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Nicolini LA, Menzaghi B, Ricci E, Pontali E, Cenderello G, Orofino G, Cascio A, Pellicanò GF, Valsecchi L, Molteni C, Vichi F, Bonfanti P, Di Biagio A. Prevalence of HDV infection in people living with HIV: Data from a multicenter Italian cohort. Front Med (Lausanne) 2023; 10:1086012. [PMID: 36778739 PMCID: PMC9911436 DOI: 10.3389/fmed.2023.1086012] [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: 10/31/2022] [Accepted: 01/13/2023] [Indexed: 01/28/2023] Open
Abstract
Objectives The development of novel antiviral agents active against Hepatitis Delta Virus (HDV) might change the natural history of chronic infection, reducing the risk for end-stage liver disease. People living with HIV (PWH) are at risk for bloodborne pathogens infection, but limited data on epidemiology of HDV infection is available in this setting. The aim of this study was to investigate HDV prevalence and attitude toward HDV testing and treatment in infectious diseases centers. Methods A cross sectional survey was performed among centers participating in the CISAI (Coordinamento Italiano per lo Studio dell'Allergia in Infezione da HIV) Group. The survey addressed anti-HDV prevalence and HDV-RNA detectability rates in PWH as well as perceived obstacles to treatment. Results Overall, responses from ten sites were collected. Among participating centers, 316 PWH with HBV chronic infection are currently followed. Of them, 15.2% had positive anti-HDV antibodies, while 13.9% were not tested yet. Overall, 17% of anti-HDV positive PWH tested at least once for HDV-RNA had active HDV infection, and 71% of them had advanced liver disease. Most infectious diseases centers intend to treat locally HDV infection with upcoming anti-HDV drugs, but some concerns exist regarding treatment schedule. Discussion HDV testing needs to be implemented in PWH. At present, few patients followed in the CISAI centers seem to be candidate to receive new direct active anti-HDV agents, but repeated HDV-RNA measures could change this proportion.
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Affiliation(s)
- Laura Ambra Nicolini
- Unit of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy,*Correspondence: Laura Ambra Nicolini,
| | - Barbara Menzaghi
- Unit of Infectious Diseases, ASST Della Valle Olona—Busto Arsizio (VA), Busto Arsizio, Italy
| | | | - Emanuele Pontali
- Department of Infectious Diseases, Galliera Hospital, Genoa, Italy
| | | | - Giancarlo Orofino
- Division I of Infectious and Tropical Diseases, ASL Città di Torino, Torino, Italy
| | - Antonio Cascio
- Unit of Infectious Diseases, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Giovanni Francesco Pellicanò
- Unit of Infectious Diseases, Department of Human Pathology of the Adult and the Developmental Age “G. Barresi”, The University of Messina, Messina, Italy
| | - Laura Valsecchi
- 1st Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy
| | - Chiara Molteni
- Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy
| | - Francesca Vichi
- Department of Infectious Diseases, SOC 1 USLCENTRO Firenze, Santa Maria Annunziata Hospital, Florence, Italy
| | - Paolo Bonfanti
- Infectious Diseases Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy,University of Milano-Bicocca, Milan, Italy
| | - Antonio Di Biagio
- Unit of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy,Department of Health Science (Dissal), University of Genoa, Genoa, Italy
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Paolini E, Longo M, Corsini A, Dongiovanni P. The Non-Invasive Assessment of Circulating D-Loop and mt-ccf Levels Opens an Intriguing Spyhole into Novel Approaches for the Tricky Diagnosis of NASH. Int J Mol Sci 2023; 24:ijms24032331. [PMID: 36768654 PMCID: PMC9916898 DOI: 10.3390/ijms24032331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/26/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide affecting both adults and children. Nowadays, no therapeutic strategies have been approved for NAFLD management, and hepatic biopsy remains the gold standard procedure for its diagnosis. NAFLD is a multifactorial disease whose pathogenesis is affected by environmental and genetic factors, and it covers a spectrum of conditions ranging from simple steatosis up to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several studies underlined the urgent need to develop an NAFLD risk prediction model based on genetics, biochemical indicators, and metabolic disorders. The loss of mitochondrial dynamics represents a typical feature of progressive NAFLD. The imbalance of mitochondrial lifecycle together with the impairment of mitochondrial biomass and function trigger oxidative stress, which in turn damages mitochondrial DNA (mtDNA). We recently demonstrated that the main genetic predictors of NAFLD led to mitochondrial dysfunction. Moreover, emerging evidence shows that variations in the displacement loop (D-loop) region impair mtDNA replication, and they have been associated with advanced NAFLD. Finally, lower levels of mitophagy foster the overload of damaged mitochondria, resulting in the release of cell-free circulating mitochondrial DNA (mt-ccf) that exacerbates liver injury. Thus, in this review we summarized what is known about D-loop region alterations and mt-ccf content during NAFLD to propose them as novel non-invasive biomarkers.
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Affiliation(s)
- Erika Paolini
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milano, Italy
| | - Miriam Longo
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milano, Italy
| | - Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milano, Italy
- IRCCS Multimedica, 20099 Milan, Italy
| | - Paola Dongiovanni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy
- Correspondence: ; Tel.: +39-02-5503-3467; Fax: +39-02-5032-0296
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Wang K, Dong Y, Han H, Cao J, Bao J, Wang WP. Clinical application of two dimensional shear wave elastography with a propagation map in evaluating liver fibrosis in patients with liver tumors. Clin Hemorheol Microcirc 2023; 85:93-104. [PMID: 35723093 DOI: 10.3233/ch-221511] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection. METHODS AND MATERIALS From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis. RESULTS The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0 kPa vs. 9.4 kPa, p < 0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6 kPa vs. 6.0 kPa, p < 0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (r = 0.834, p < 0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0-S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6 kPa, respectively. The areas under the ROC curve of S≥1, S≥2, S≥3, and S = 4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S≥1, S≥2, S≥3, and S = 4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa. CONCLUSION 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection.
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Affiliation(s)
- Kun Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Institute of Ultrasound Medicine and Engineering, Fudan University, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Hong Han
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Jiaying Cao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
| | - Jingwen Bao
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
- Institute of Ultrasound Medicine and Engineering, Fudan University, Shanghai, China
- Shanghai Institute of Medical Imaging, Shanghai, China
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25
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Kim-Jun Teh K, Pik-Eu Chang J, Boon-Bee Goh G. Noninvasive assessment of liver disease severity: image-related. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:3-29. [DOI: 10.1016/b978-0-323-98368-6.00014-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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26
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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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Hepatic steatosis leads to overestimation of liver stiffness measurement in both chronic hepatitis B and metabolic-associated fatty liver disease patients. Clin Res Hepatol Gastroenterol 2022; 46:101957. [PMID: 35609821 DOI: 10.1016/j.clinre.2022.101957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/12/2022] [Accepted: 05/20/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND The impact of hepatic steatosis on liver stiffness measurement (LSM) in both chronic hepatitis B(CHB) and metabolic-associated fatty liver disease (MAFLD) remains controversial. AIMS To determine whether LSM is affected by hepatic steatosis in CHB-MAFLD. METHODS Hepatic steatosis and liver fibrosis were assessed by histological and noninvasively methods. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance of LSM. RESULTS The prevalence of MAFLD in CHB patients (n = 436)was 47.5% (n = 207). For patients with low amounts of fibrosis (F0-1 and F0-2), the median LSM was 8.8 kPa and 9.2 kPa in patients with moderate- severe steatosis,which was significantly higher than that in patients with none-mild steatosis (P < 0.05) . The positive predictive value(PPV) was lower for LSM identifying significant fibrosis (F ≥ 2) as well as severe fibrosis (F ≥ 3) in group which controlled attenuation parameter(CAP) ≥ 268 dB/m than its counterpart(68.2% vs 84.6% and 24.3% vs 45.0%). The AUROC of LSM detected F ≥ 2 was 0.833 at a cutoff of 8.8 kPa and 0.873 at a cutoff of 7.0 kPa in patients with CAP ≥ 268 and CAP < 268, respectively. CONCLUSIONS The presence of moderate-severe steatosis, detected by histology or CAP, should be taken into account to avoid overestimation of LSM.
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Kristensen H, Kimer N, Møller S. Indications and methods for measuring portal hypertension in cirrhosis. Scand J Gastroenterol 2022; 57:1149-1157. [PMID: 35514215 DOI: 10.1080/00365521.2022.2065889] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Over the last decade our understanding of the pathophysiology of portal hypertension has increased. Novel diagnostic technologies have facilitated and improved the diagnosis and treatment of hepatic fibrosis and cirrhosis. With this review we aim to provide an overview of contemporary diagnostic principles of portal hypertension and indications for measuring portal pressure in cirrhosis.Methods: By review of current literature, we assessed new and old principles of measuring portal hypertension and the diagnostic values of the methods.Results: Invasive measurement of the portal pressure is still the gold standard to quantitate portal hypertension and to assess response to vasoactive treatment. The size of the portal pressure is important to assess since it contains information on the course of the disease and risk of developing hepatic decompensation, hepatocellular carcinoma, and mortality. Reliable non-invasive Elastography techniques are emerging that adequately assess portal pressure, but the available methods are not yet sufficiently accurate.Conclusion: Although elastography techniques provide valuable information and are good monitoring tools, liver vein catheterization remains valuable in diagnosing and monitoring portal hypertension, especially in combination with a trans-jugular liver biopsy.
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Affiliation(s)
- Helle Kristensen
- Gastro Unit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine, Center of Functional Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark.,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Damjanovska S, Karb DB, Tripathi A, Asirwatham J, Delozier S, Perez JA, Falck-Ytter Y, Cohen S. Accuracy of Ultrasound Elastography and Fibrosis-4 Index (FIB-4) in Ruling Out Cirrhosis in Obese Non-Alcoholic Fatty Liver Disease (NAFLD) Patients. Cureus 2022; 14:e29445. [PMID: 36299964 PMCID: PMC9587692 DOI: 10.7759/cureus.29445] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of advanced liver disease in the USA. Liver biopsy, the gold standard diagnostic test for evaluating liver fibrosis, is associated with significant risk and expense. The accuracy of ultrasound elastography and Fibrosis-4 index (FIB-4) in the obese NAFLD population is unknown. We aimed to compare the accuracy of ultrasound elastography and FIB-4 to liver biopsy in ruling out cirrhosis in NAFLD patients at a tertiary, transplant referral center in the US. Methods: We retrospectively evaluated 93 patients with a mean age of 53 years (SD: 13 years) who underwent liver ultrasound elastography and liver biopsy, and additionally calculated their FIB-4 at the time of biopsy. We compared the liver stiffness measurement (LSM) obtained from ultrasound elastography and FIB-4 with the pathology results for ruling out cirrhosis. Results: 85% of the patients were white, 53% were female, average BMI was 34.7 (SD: 6.7), 52% had diabetes, and 53% had hypertension. For biopsy-proven cirrhosis (prevalence 15%), a cut-off value of 12.5 kilopascals (kPa) for F4 had a sensitivity of 92% and a specificity of 54%. Values below this threshold excluded cirrhosis with 98% certainty. Compared to FIB-4, ultrasound elastography showed higher accuracy in ruling out cirrhosis (92% vs. 80% sensitivity, 98% vs. 95% negative predictive value (NPV), respectively). Conclusion: To our knowledge, this is the first study in a tertiary transplant referral center in the USA to show that ultrasound elastography was superior to FIB-4 and can be used as a reliable screening test to rule out cirrhosis in obese NAFLD patients at a 12.5 kPa cut-off. Therefore, helping to avoid the risk and expense associated with liver biopsy.
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Guerrero L, Paradela A, Corrales FJ. Targeted Proteomics for Monitoring One-Carbon Metabolism in Liver Diseases. Metabolites 2022; 12:metabo12090779. [PMID: 36144184 PMCID: PMC9501948 DOI: 10.3390/metabo12090779] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/18/2022] [Accepted: 08/19/2022] [Indexed: 11/16/2022] Open
Abstract
Liver diseases cause approximately 2 million deaths per year worldwide and had an increasing incidence during the last decade. Risk factors for liver diseases include alcohol consumption, obesity, diabetes, the intake of hepatotoxic substances like aflatoxin, viral infection, and genetic determinants. Liver cancer is the sixth most prevalent cancer and the third in mortality (second in males). The low survival rate (less than 20% in 5 years) is partially explained by the late diagnosis, which remarks the need for new early molecular biomarkers. One-carbon metabolism integrates folate and methionine cycles and participates in essential cell processes such as redox homeostasis maintenance and the regulation of methylation reactions through the production of intermediate metabolites such as cysteine and S-Adenosylmethionine. One-carbon metabolism has a tissue specific configuration, and in the liver, the participating enzymes are abundantly expressed—a requirement to maintain hepatocyte differentiation. Targeted proteomics studies have revealed significant differences in hepatocellular carcinoma and cirrhosis, suggesting that monitoring one-carbon metabolism enzymes can be useful for stratification of liver disease patients and to develop precision medicine strategies for their clinical management. Here, reprogramming of one-carbon metabolism in liver diseases is described and the role of mass spectrometry to follow-up these alterations is discussed.
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Affiliation(s)
- Laura Guerrero
- Centro Nacional de Biotecnología (CNB), CSIC. C/Darwin 3, 28049 Madrid, Spain
| | - Alberto Paradela
- Centro Nacional de Biotecnología (CNB), CSIC. C/Darwin 3, 28049 Madrid, Spain
| | - Fernando J. Corrales
- Centro Nacional de Biotecnología (CNB), CSIC. C/Darwin 3, 28049 Madrid, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-91-585-46-96
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Rossi C, Salvati A, Distaso M, Campani D, Raggi F, Biancalana E, Tricò D, Brunetto MR, Solini A. The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage. Int J Mol Sci 2022; 23:ijms23137447. [PMID: 35806450 PMCID: PMC9267345 DOI: 10.3390/ijms23137447] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 12/03/2022] Open
Abstract
P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage.
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Affiliation(s)
- Chiara Rossi
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (C.R.); (M.D.); (F.R.)
| | - Antonio Salvati
- Azienda Ospedaliero-Universitaria Pisana, I-56126 Pisa, Italy;
| | - Mariarosaria Distaso
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (C.R.); (M.D.); (F.R.)
| | - Daniela Campani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, I-56126 Pisa, Italy;
| | - Francesco Raggi
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (C.R.); (M.D.); (F.R.)
| | - Edoardo Biancalana
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (E.B.); (D.T.)
| | - Domenico Tricò
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (E.B.); (D.T.)
| | - Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (E.B.); (D.T.)
- Correspondence: (M.R.B.); (A.S.); Tel.: +39-050-996857 (M.R.B.); +39-050-993482 (A.S.); Fax: +39-050-553235 (A.S.)
| | - Anna Solini
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, I-56126 Pisa, Italy; (C.R.); (M.D.); (F.R.)
- Correspondence: (M.R.B.); (A.S.); Tel.: +39-050-996857 (M.R.B.); +39-050-993482 (A.S.); Fax: +39-050-553235 (A.S.)
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Peng X, Tian A, Li J, Mao Y, Jiang N, Li T, Mao X. Diagnostic Value of FibroTouch and Non-invasive Fibrosis Indexes in Hepatic Fibrosis with Different Aetiologies. Dig Dis Sci 2022; 67:2627-2636. [PMID: 34059990 DOI: 10.1007/s10620-021-07049-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 05/09/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Liver biopsy is the gold standard for staging liver fibrosis, but it has numerous drawbacks, mainly associated with bleeding and bile fistula risks. A number of non-invasive techniques have been investigated, but they all have their own disadvantages. To avoid the risks mentioned above and to improve the diagnostic value, we still need to search for a more accurate non-invasive method to evaluate the degree of liver fibrosis. AIM This study aimed to evaluate the diagnostic performance of FibroTouch versus other non-invasive fibrosis indexes in hepatic fibrosis of different aetiologies. METHODS This study retrospectively enrolled 227 patients with chronic hepatic liver disease admitted to the first hospital of Lanzhou University from 2017 to 2020. Liver biopsy was performed in all of the patients, and their biochemical indicators were all tested. Non-invasive indexes including the fibrosis index based on four factors (FIB-4), the aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio index (GPRI) were all calculated. Transient elastography was performed using FibroTouch. RESULTS The correlation between FibroTouch and the pathology of liver fibrosis was significantly higher than that between the non-invasive fibrosis indexes and the biopsy results (r = 0.771, p < 0.05). The area under the receiver operating curve (AUC) of FibroTouch was significantly higher than that of FIB-4, APRI, and GPRI for the diagnosis of significant fibrosis (≥ S2 fibrosis stage), advanced fibrosis (≥ S3 fibrosis stage), and cirrhosis (= S4 fibrosis stage) (p < 0.05). The patients were grouped according to different aetiologies. The diagnostic value of FibroTouch had much higher credibility in different fibrosis stages for different causes compared with other non-invasive indexes. The AUC of FibroTouch showed both higher specificity and higher sensitivity than FIB-4, APRI, and GPRI for different liver fibrosis stages with different aetiologies. CONCLUSIONS FibroTouch demonstrates the highest diagnostic value for liver fibrosis and cirrhosis among non-invasive methods, showing better results than FIB-4, APRI, and GPRI, and surpassed only by liver biopsy. FibroTouch is reliable in assessing liver fibrosis with different aetiologies.
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Affiliation(s)
- Xuebin Peng
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Aiping Tian
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Junfeng Li
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Yongwu Mao
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Ni Jiang
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Ting Li
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Xiaorong Mao
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
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Lee DH, Sung SU, Lee YK, Lim IH, Jang H, Joo SK, Park JH, Chang MS, So YH, Kim W. A sequential approach using the age-adjusted fibrosis-4 index and vibration-controlled transient elastography to detect advanced fibrosis in Korean patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2022; 55:994-1007. [PMID: 35005800 DOI: 10.1111/apt.16766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 09/02/2021] [Accepted: 12/24/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Vibration-controlled transient elastography (VCTE) has shown good diagnostic performance in predicting fibrosis stages in patients with non-alcoholic fatty liver disease (NAFLD). However, an optimal diagnostic approach to detect advanced fibrosis in patients with NAFLD has not been established. APPROACH AND RESULTS We prospectively collected data from 539 subjects who underwent liver biopsy at a single centre between January 2014 and December 2019. Diagnostic performance was estimated using the area under the receiver-operating characteristic curve (AUROC). Several models combining the fibrosis 4 index (FIB-4) score and liver stiffness measurement (LSM) were analysed to reduce the need for unnecessary liver biopsies. We observed significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) in 173 (32.1%), 74 (13.7%) and 46 subjects (8.5%), respectively. The AUROCs (95% CI) for LSMs to diagnose ≥F2, ≥F3 and F4 were 0.82 (0.78-0.85), 0.92 (0.89-0.94) and 0.95 (0.93-0.97), respectively. Optimal LSM cut-off values were 6.7 (≥F2), 8.3 (≥F3) and 9.8 (F4) kPa. LSMs were affected by waist circumference, serum albumin and fibrosis stage (R2 = 0.315). Abdominal obesity, elevated transaminase, diabetes mellitus and high IQR/Median were associated with the discordance of ≥2 fibrosis stages between LSMs and histologic data. The sequential use of the age-adjusted FIB-4 and LSMs yielded the least uncertainty (5.3%) in classifying disease severity with the highest diagnostic accuracy (81%) among a variety of non-invasive test combinations. CONCLUSIONS The sequential approach of age-adjusted FIB-4 and VCTE could represent a practical diagnostic strategy to detect advanced fibrosis in NAFLD (ClinicalTrials.gov #NCT02206841).
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Affiliation(s)
- Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Se Un Sung
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yun Kyu Lee
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ik Hyeon Lim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Heejoon Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Sae Kyoung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Jeong Hwan Park
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Mee Soo Chang
- Department of Pathology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Young Ho So
- Department of Radiology, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea
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Cardoso AC, Figueiredo-Mendes C, Villela-Nogueira CA, Marcellin P. Staging Fibrosis in Chronic Viral Hepatitis. Viruses 2022; 14:v14040660. [PMID: 35458391 PMCID: PMC9025777 DOI: 10.3390/v14040660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 02/06/2023] Open
Abstract
Staging fibrosis accurately has always been a challenge in viral hepatitis and other liver diseases. Liver biopsy is an imperfect gold standard due to its intra and interobserver agreement limitations and additional characteristics such as its safety and cost. Hence, non-invasive tests have been developed to stage liver fibrosis. In addition to serological biomarkers, physical tests with reasonable accuracy are available and adopted in the daily clinic regarding viral hepatitis fibrosis staging. In this review, we discuss the published data regarding the staging of liver fibrosis in chronic hepatitis B and C, emphasizing non-invasive markers of fibrosis, both serological and physical. Moreover, we also discuss a persistent central gap, the evaluation of liver fibrosis after HCV cure.
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Affiliation(s)
- Ana Carolina Cardoso
- Postgraduate Internal Medicine Program, Hepatology Division, Clementino Fraga Filho University Hospital, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Brazil
- Correspondence:
| | - Claudio Figueiredo-Mendes
- Hepatology Division, General Hospital, Santa Casa da Misericórdia do Rio de Janeiro, Rio de Janeiro 20020-022, Brazil;
| | - Cristiane A. Villela-Nogueira
- Internal Medicine Department, Hepatology Division, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Brazil;
| | - Patrick Marcellin
- Hepatology Department, Hôpital Beaujon, APHP, INSERM, University of Paris, 92110 Clichy, France;
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Zhou J, Yan F, Xu J, Lu Q, Zhu X, Gao B, Zhang H, Yang R, Luo Y. Diagnosis of steatohepatitis and fibrosis in biopsy-proven nonalcoholic fatty liver diseases: including two-dimension real-time shear wave elastography and noninvasive fibrotic biomarker scores. Quant Imaging Med Surg 2022; 12:1800-1814. [PMID: 35284290 PMCID: PMC8899947 DOI: 10.21037/qims-21-700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 10/22/2021] [Indexed: 11/15/2023]
Abstract
BACKGROUND The aim of this retrospective study was to evaluate the accuracy of two-dimension real-time shear wave elastography (2D-SWE) for the diagnosis of steatohepatitis and fibrosis in a cohort patients confirmed nonalcoholic fatty liver diseases (NAFLD) by liver biopsy, and compare with four noninvasive fibrotic biomarker scores (NFS, FIB-4, BARD and APRI). METHODS 116 NAFLD patients and 23 normal control group were enrolled. The diagnostic performance of 2D-SWE and four noninvasive fibrotic biomarker scores was evaluated based on histopathological inflammation grades and fibrosis stages (F) according to Kleiner/Brunt et al.'s criteria classification. 5-fold cross validation and receiver operating characteristics curve (ROC) analyses were used to obtain an assessment of 2D-SWE and four noninvasive fibrotic biomarker scores; then cross validated area under the curves (AUCs) were compared using the test of Delong. Meanwhile, influence of steatosis on liver stiffness measurement (LSM) of 2D-SWE was also studied. RESULTS Liver stiffness measured by 2D-SWE proved to be an excellent diagnostic indicator for detecting steatohepatitis (AUROC =0.88), and fibrosis: ≥F2 stage (AUROC =0.86), ≥F3 stage (AUROC =0.89) and =F4 stage (AUROC =0.90) with the cutoff values were 7.3, 10.0, 11.6 and 12.6 kPa, respectively. Compared with fibrotic scores, 2D-SWE had the highest AUROC for predicting ≥F2, ≥F3, =F4 by Delong test (all P<0.05). No statistic differences of LSM were found among different steatosis levels (P=0.97). CONCLUSIONS The stiffness measured by 2D-SWE could be used to noninvasively identify steatohepatitis and stage fibrosis in NAFLD patients. Moreover, the diagnosis efficiency of the stiffness measured by 2D-SWE could not be influenced by steatosis.
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Affiliation(s)
- Jie Zhou
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Feng Yan
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Jinshun Xu
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Qiang Lu
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Xianglan Zhu
- Pathology Department of West China Hospital of Sichuan University, Chengdu, China
| | - Binyang Gao
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Huan Zhang
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Rui Yang
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
| | - Yan Luo
- Ultrasound Department of West China Hospital of Sichuan University, Chengdu, China
- Laboratory of Ultrasound Imaging of West China Hospital of Sichuan University, Chengdu, China
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Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus. J Med Ultrason (2001) 2022; 49:253-259. [PMID: 35129720 PMCID: PMC9038899 DOI: 10.1007/s10396-021-01188-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/28/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE). METHODS Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma. RESULTS The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis. CONCLUSION In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.
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Tokorodani R, Kume T, Daikoku K, Oka M. [Evaluation of the Validity of ROI Setting in CEI Used for the Assessment of Liver]. Nihon Hoshasen Gijutsu Gakkai Zasshi 2022; 78:44-52. [PMID: 35046221 DOI: 10.6009/jjrt.780105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE The enhancement effect ratio using ethoxybenzyl (EOB) contrast is useful in the assessment of liver fibrosis. Since the enhancement effect ratio is calculated by setting a region of interest (ROI) in the liver, the ROI setting method may affect the enhancement effect ratio. One of the methods of setting the ROI in liver fibrosis evaluation is by placing the ROI in each Quinault segment, but this method requires considerable time. Therefore, it is necessary to consider a reproducible ROI setting method in contrast to the method of placing ROIs in each Quinault segment. METHOD In contrast to the method of placing one ROI in each Quinault segment, we examined the method of setting four ROIs (two in the right lobe and two in the left lobe) and two ROIs (one in the right lobe and one in the left lobe). The size of the ROI was set to 1 cm2, 4 cm2, and the maximum area that fits within each placement area. CONCLUSION In the ROI setting method for CEI calculation, reproducibility can be maintained by setting the number of ROIs in four locations and by setting ROIs of 4 cm2 or more.
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Affiliation(s)
- Ryotaro Tokorodani
- Division of Radiology, Department of Medical Technology, Kochi Medical School Hospital
| | - Toshiaki Kume
- Department of Radiological Technology, Kochi Health Sciences Center
| | - Kazuki Daikoku
- Division of Radiology, Department of Medical Technology, Kochi Medical School Hospital
| | - Masaki Oka
- Department of Radiological Technology, Kochi Health Sciences Center
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Boursier J, Decraecker M, Bourlière M, Bureau C, Ganne-Carrié N, de Lédinghen V. Quality criteria for the measurement of liver stiffness. Clin Res Hepatol Gastroenterol 2022; 46:101761. [PMID: 34325013 DOI: 10.1016/j.clinre.2021.101761] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/23/2021] [Indexed: 02/04/2023]
Abstract
Liver elastography offers the possibility of a quick, non-invasive, and painless evaluation of the liver with immediate results at bedside. Transient elastography is the most validated technology, and many others such as point shear wave elastography, 2D-shear wave elastography, or magnetic resonance elastography have been developed. To ensure the best evaluation, several conditions of examination must be respected for liver stiffness measurement. Indeed, patient, operator and examination characteristics have all been shown to influence the result of liver stiffness measurement. Food intake increases liver stiffness, whereas withdrawal in alcoholics is associated with a decrease in elastography results. Inter-observer reproducibility of the measurement seems suboptimal, and the influence of the operator experience is still being debated. The measurement site and the FibroScan® probe must be correctly chosen. Finally, the intrinsic characteristics and quality criteria of the measurement, especially the interquartile range/median ratio, must be carefully checked to avoid overestimation of liver stiffness. Most of the results come from studies which have evaluated transient elastography, with less data available for the other technologies. Liver stiffness measurement could appear as a simple way to explore the liver, but several conditions must be met before deciding the patient management according to its result.
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Affiliation(s)
- Jérôme Boursier
- Laboratoire HIFIH, UPRES EA3859, SFR ICAT 4208, Université d'Angers, Angers, France.
| | - Marie Decraecker
- Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, pessac & INSERM U1053, Université de Bordeaux, Bordeaux, France
| | - Marc Bourlière
- Service d'hépato-gastroentérologie, Hôpital Saint Joseph & INSERM UMR 1252 IRD SESSTIM Aix Marseille Université, Marseille, France
| | - Christophe Bureau
- Service d'hépatologie, Hôpital Rangueil, CHU Toulouse, Toulouse, France
| | - Nathalie Ganne-Carrié
- Service d'hépatologie, Hôpital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny & INSERM UMR 1138, Centre de Recherche des Cordeliers, Université de Paris, France
| | - Victor de Lédinghen
- Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, CHU Bordeaux, pessac & INSERM U1053, Université de Bordeaux, Bordeaux, France
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A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure. Am J Gastroenterol 2022; 117:138-146. [PMID: 34817975 DOI: 10.14309/ajg.0000000000001503] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 08/03/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR. METHODS Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months). RESULTS Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007). DISCUSSION We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.
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Ahumada A, Rayón L, Usón C, Bañares R, Alonso Lopez S. Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long? World J Gastroenterol 2021; 27:6737-6749. [PMID: 34790004 PMCID: PMC8567476 DOI: 10.3748/wjg.v27.i40.6737] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/24/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) chronic infection is associated with fibrosis progression, end-stage liver complications and HCC. Not surprisingly, HCV infection is a leading cause of liver-related morbidity and mortality worldwide. After sustained virological response (SVR), the risk of developing hepatocellular carcinoma is not completely eliminated in patients with established cirrhosis or with advanced fibrosis. Therefore, lifelong surveillance is currently recommended. This strategy is likely not universally cost-effective and harmless, considering that not all patients with advanced fibrosis have the same risk of developing HCC. Factors related to the severity of liver disease and its potential to improve after SVR, the molecular and epigenetic changes that occur during infection and other associated comorbidities might account for different risk levels and are likely essential for identifying patients who would benefit from screening programs after SVR. Efforts to develop predictive models and risk calculators, biomarkers and genetic panels and even deep learning models to estimate the individual risk of HCC have been made in the direct-acting antiviral agents era, when thousands of patients with advanced fibrosis and cirrhosis have reached SVR. These tools could help to identify patients with very low HCC risk in whom surveillance might not be justified. In this review, factors affecting the probability of HCC development after SVR, the benefits and risks of surveillance, suggested strategies to estimate individualized HCC risk and the current evidence to recommend lifelong surveillance are discussed.
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Affiliation(s)
- Adriana Ahumada
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
- Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
| | - Laura Rayón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
| | - Clara Usón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
| | - Rafael Bañares
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
- Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
- Medicine, Universidad Complutense de Madrid, Madrid 28006, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Sonia Alonso Lopez
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain
- Liver Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid 28007, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid 28029, Spain
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Fang JM, Cheng J, Chang MF, Ahn J, Westerhoff M. Transient elastography versus liver biopsy: discordance in evaluations for fibrosis and steatosis from a pathology standpoint. Mod Pathol 2021; 34:1955-1962. [PMID: 34108635 DOI: 10.1038/s41379-021-00851-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/19/2021] [Accepted: 05/21/2021] [Indexed: 11/09/2022]
Abstract
Vibration-controlled transient elastography (VCTE) is a non-invasive method of evaluating liver fibrosis and steatosis. It can easily be performed in the outpatient setting and has been suggested as an alternative to liver biopsy. However, VCTE and biopsy discrepancies commonly occur. Patient characteristics, procedure performance, and liver features can impact the reliability of VCTE results. We identified 82 patients who received VCTE and biopsy within one month to assess how frequently major discrepancies occur and to determine the role of the liver biopsy in this workup. In our study, 35.4% of patients had a major fibrosis discrepancy, which was defined as advanced fibrosis or cirrhosis by VCTE and no to minimal fibrosis on biopsy. This was significantly associated with increased BMI, and liver features including steatohepatitis, inflammation, congestion, and cholestasis were important contributors to discrepancies. All patients with advanced fibrosis or cirrhosis on liver biopsy were appropriately detected by VCTE (n = 28). Detection of steatosis was less sensitive as 19% (n = 4 of 21) of patients with moderate to severe steatosis on biopsy were missed by VCTE. Liver biopsy has been traditionally performed for diagnosis, but with the emergence of non-invasive tools to evaluate for liver fibrosis and steatosis, biopsies are now additionally being performed to confirm findings from noninvasive procedures. Although VCTE is a highly sensitive tool for liver fibrosis, it is not as specific, and therefore, the liver biopsy remains the gold standard for accurate fibrosis assessment.
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Affiliation(s)
- Jiayun M Fang
- Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA.
| | - Jerome Cheng
- Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA
| | - Michael F Chang
- Department of Internal Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Joseph Ahn
- Department of Internal Medicine, Oregon Health & Science University, Portland, OR, USA
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Davis TME. Diabetes and metabolic dysfunction-associated fatty liver disease. Metabolism 2021; 123:154868. [PMID: 34400217 DOI: 10.1016/j.metabol.2021.154868] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/08/2021] [Accepted: 08/10/2021] [Indexed: 12/20/2022]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a relatively novel classification which downplays the importance of alcohol in the definition of non-alcoholic fatty liver disease (NAFLD) and emphasizes the metabolic risk factors that underlie progression of NAFLD-associated pathology. All people with type 2 diabetes (T2D) and hepatic fat content >5% by biomarkers, imaging or biopsy are considered to have MAFLD. Since there have been very few published studies of MAFLD in diabetes, the present review assesses contemporary methods for quantifying liver fat and fibrosis (including those based on magnetic resonance imaging) with special reference to T2D, their prognostic implications for people with T2D and MAFLD, and the factors and interventions that modify disease progression and outcomes. The changing epidemiology of obesity and cardiovascular disease and new therapies for MAFLD on the horizon with potential implications for T2D are discussed.
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Affiliation(s)
- Timothy M E Davis
- University of Western Australia, Medical School, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia.
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Garteiser P, Pagé G, d'Assignies G, Leitao HS, Vilgrain V, Sinkus R, Van Beers BE. Necro-inflammatory activity grading in chronic viral hepatitis with three-dimensional multifrequency MR elastography. Sci Rep 2021; 11:19386. [PMID: 34588519 PMCID: PMC8481240 DOI: 10.1038/s41598-021-98726-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 09/14/2021] [Indexed: 12/19/2022] Open
Abstract
The purpose of this study was to assess the diagnostic value of multifrequency MR elastography for grading necro-inflammation in the liver. Fifty participants with chronic hepatitis B or C were recruited for this institutional review board-approved study. Their liver was examined with multifrequency MR elastography. The storage, shear and loss moduli, and the damping ratio were measured at 56 Hz. The multifrequency wave dispersion coefficient of the shear modulus was calculated. The measurements were compared to reference markers of necro-inflammation and fibrosis with Spearman correlations and multiple regression analysis. Diagnostic accuracy was assessed. At multiple regression analysis, necro-inflammation was the only determinant of the multifrequency dispersion coefficient, whereas fibrosis was the only determinant of the storage, loss and shear moduli. The multifrequency dispersion coefficient had the largest AUC for necro-inflammatory activity A ≥ 2 [0.84 (0.71-0.93) vs. storage modulus AUC: 0.65 (0.50-0.79), p = 0.03], whereas the storage modulus had the largest AUC for fibrosis F ≥ 2 [AUC (95% confidence intervals) 0.91 (0.79-0.98)] and cirrhosis F4 [0.97 (0.88-1.00)]. The measurement of the multifrequency dispersion coefficient at three-dimensional MR elastography has the potential to grade liver necro-inflammation in patients with chronic vial hepatitis.
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Affiliation(s)
- Philippe Garteiser
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149 Inserm, Université de Paris, 75018, Paris, France.
| | - Gwenaël Pagé
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149 Inserm, Université de Paris, 75018, Paris, France
| | - Gaspard d'Assignies
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149 Inserm, Université de Paris, 75018, Paris, France
- Department of Radiology, Beaujon University Hospital Paris Nord, AP-HP, 92110, Clichy, France
| | - Helena S Leitao
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149 Inserm, Université de Paris, 75018, Paris, France
- Department of Radiology, Beaujon University Hospital Paris Nord, AP-HP, 92110, Clichy, France
| | - Valérie Vilgrain
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149 Inserm, Université de Paris, 75018, Paris, France
- Department of Radiology, Beaujon University Hospital Paris Nord, AP-HP, 92110, Clichy, France
| | - Ralph Sinkus
- Laboratory for Vascular Translational Science, UMR 1148 Inserm, Université de Paris, 75018, Paris, France
| | - Bernard E Van Beers
- Laboratory of Imaging Biomarkers, Center for Research on Inflammation, UMR 1149 Inserm, Université de Paris, 75018, Paris, France
- Department of Radiology, Beaujon University Hospital Paris Nord, AP-HP, 92110, Clichy, France
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Cristoferi L, Calvaruso V, Overi D, Viganò M, Rigamonti C, Degasperi E, Cardinale V, Labanca S, Zucchini N, Fichera A, Di Marco V, Leutner M, Venere R, Picciotto A, Lucà M, Mulinacci G, Palermo A, Gerussi A, D’Amato D, Elisabeth O’Donnell S, Cerini F, De Benedittis C, Malinverno F, Ronca V, Mancuso C, Cazzagon N, Ciaccio A, Barisani D, Marzioni M, Floreani A, Alvaro D, Gaudio E, Invernizzi P, Carpino G, Nardi A, Carbone M. Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach. Hepatology 2021; 74:1496-1508. [PMID: 33724515 PMCID: PMC8518641 DOI: 10.1002/hep.31810] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/25/2021] [Accepted: 03/02/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. APPROACH AND RESULTS We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. CONCLUSIONS In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.
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Affiliation(s)
- Laura Cristoferi
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly,Bicocca Bioinformatics Biostatistics and Bioimaging Centre‐B4School of Medicine and SurgeryUniversity of Milan‐BicoccaMonzaItaly
| | - Vincenza Calvaruso
- Section of Gastroenterology and Hepatology, PROMISEUniversity of PalermoPalermoItaly
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly
| | - Mauro Viganò
- Division of HepatologyOspedale San GiuseppeUniversity of MilanMilanItaly
| | - Cristina Rigamonti
- Department of Translational MedicineUniversità degli Studi del Piemonte Orientale “A. Avogadro”NovaraItaly
| | - Elisabetta Degasperi
- CRC “A. M. e A. Migliavacca” Center for Liver Diseases, Division of Gastroenterology and HepatologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly
| | - Vincenzo Cardinale
- Department of Medico‐Surgical Sciences and BiotechnologiesPolo Pontino “Sapienza” University of RomeLatinaItaly
| | - Sara Labanca
- Department of Internal MedicineUniversity of GenoaGenoaItaly
| | | | - Anna Fichera
- Section of Gastroenterology and Hepatology, PROMISEUniversity of PalermoPalermoItaly
| | - Vito Di Marco
- Section of Gastroenterology and Hepatology, PROMISEUniversity of PalermoPalermoItaly
| | | | - Rosanna Venere
- Department of Precision and Translational MedicineSapienza University of RomeRomeItaly
| | | | - Martina Lucà
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Giacomo Mulinacci
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Andrea Palermo
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Alessio Gerussi
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Daphne D’Amato
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Sarah Elisabeth O’Donnell
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Federica Cerini
- Division of HepatologyOspedale San GiuseppeUniversity of MilanMilanItaly
| | - Carla De Benedittis
- Department of Translational MedicineUniversità degli Studi del Piemonte Orientale “A. Avogadro”NovaraItaly
| | - Federica Malinverno
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Vincenzo Ronca
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Clara Mancuso
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Nora Cazzagon
- Department of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly
| | - Antonio Ciaccio
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Donatella Barisani
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly
| | - Marco Marzioni
- Department of GastroenterologyUniversità Politecnica delle MarcheAnconaItaly
| | - Annarosa Floreani
- Studiosa SeniorUniversity of PaduaPaduaItaly,Scientific ConsultantIRCCS NegrarVeronaItaly
| | - Domenico Alvaro
- Department of Medico‐Surgical Sciences and BiotechnologiesPolo Pontino “Sapienza” University of RomeLatinaItaly
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly
| | - Pietro Invernizzi
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
| | - Guido Carpino
- Department of Movement, Human and Health ScienceUniversity of Rome “Foro Italico”RomeItaly
| | - Alessandra Nardi
- Department of MathematicsUniversity of Rome Tor VergataRomeItaly
| | - Marco Carbone
- Division of GastroenterologyCenter for Autoimmune Liver DiseasesDepartment of Medicine and SurgeryUniversity of Milano‐BicoccaMonzaItaly,European Reference Network on Hepatological Diseases (ERN RARE‐LIVER)San Gerardo HospitalMonzaItaly
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Kimura S, Tanaka K, Oeda S, Inoue K, Inadomi C, Kubotsu Y, Yoshioka W, Okada M, Isoda H, Kuwashiro T, Akiyama T, Kurashige A, Oshima A, Oshima M, Matsumoto Y, Kawaguchi A, Anzai K, Sueoka E, Aishima S, Takahashi H. Effect of skin-capsular distance on controlled attenuation parameter for diagnosing liver steatosis in patients with nonalcoholic fatty liver disease. Sci Rep 2021; 11:15641. [PMID: 34341368 PMCID: PMC8329228 DOI: 10.1038/s41598-021-94970-3] [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: 05/08/2021] [Accepted: 07/19/2021] [Indexed: 12/16/2022] Open
Abstract
The effect of the skin-capsular distance (SCD) on the controlled attenuation parameter (CAP) for diagnosis of liver steatosis in patients with nonalcoholic fatty liver disease (NAFLD) remains unclear. The SCD was measured using B-mode ultrasound, and the CAP was measured using the M probe of FibroScan®. According to the indications of the M probe, 113 patients with an SCD of ≤ 25 mm were included in the present study. The association between the SCD and CAP was investigated, and the diagnostic performance of the SCD-adjusted CAP was tested. The SCD showed the most significant positive correlation with the CAP (ρ = 0.329, p < 0.001). In the multiple regression analysis, the SCD and serum albumin concentration were associated with the CAP, independent of pathological liver steatosis. According to the multivariate analysis, two different formulas were developed to obtain the adjusted CAP using the SCD and serum albumin concentration as follows: adjusted CAP (dB/m) = CAP - (5.26 × SCD) and adjusted CAP (dB/m) = CAP - (5.35 × SCD) - (25.77 × serum albumin concentration). The area under the receiver operating characteristic curve for diagnosis of a steatosis score ≥ 2 of adjusted CAP was 0.678 and 0.684 respectively, which were significantly greater than the original CAP (0.621: p = 0.030 and p = 0.024). The SCD is associated with the CAP independent of liver steatosis. Adjustment of the CAP using the SCD improves the diagnostic performance of the CAP in NAFLD.
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Affiliation(s)
- Syunichiro Kimura
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Kenichi Tanaka
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Satoshi Oeda
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
| | - Kaori Inoue
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Chika Inadomi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Yoshihito Kubotsu
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Wataru Yoshioka
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Michiaki Okada
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Hiroshi Isoda
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Takuya Kuwashiro
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Takumi Akiyama
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Aya Kurashige
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Ayaka Oshima
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Mayumi Oshima
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Yasue Matsumoto
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Atsushi Kawaguchi
- Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Keizo Anzai
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Eisaburo Sueoka
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
- Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Shinichi Aishima
- Department of Pathology & Microbiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
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Galina P, Alexopoulou E, Mentessidou A, Mirilas P, Zellos A, Lykopoulou L, Patereli A, Salpasaranis K, Kelekis NL, Zarifi M. Diagnostic accuracy of two-dimensional shear wave elastography in detecting hepatic fibrosis in children with autoimmune hepatitis, biliary atresia and other chronic liver diseases. Pediatr Radiol 2021; 51:1358-1368. [PMID: 33755748 DOI: 10.1007/s00247-020-04959-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/13/2020] [Accepted: 12/22/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although fibrosis is the main determinant of liver stiffness, other disease-related factors usually disregarded in studies on liver elastography, such as inflammation and cholestasis, may influence liver stiffness. OBJECTIVE To evaluate the accuracy of two-dimensional (2-D) shear wave elastography in assessing liver fibrosis in children with chronic liver disease by controlling for the confounding role of several disease- and patient-related factors. MATERIALS AND METHODS Three disease groups were studied: 1) various chronic liver diseases, 2) autoimmune hepatitis and 3) biliary atresia. The METAVIR (meta-analysis of histological data in viral hepatitis) score was used for fibrosis staging and grading of necroinflammatory activity. Multiple linear regression was used to evaluate the relationship between liver stiffness measurements and disease-related factors. The diagnostic accuracy of elastography for predicting fibrosis stages was assessed by calculating the area under the receiver operating characteristic curves. RESULTS The various chronic liver diseases group (n=32; 7.1±4.9 [mean±standard deviation] years) showed liver stiffness of 8.9±5.0 (mean±standard deviation) kPa, the autoimmune hepatitis group (n=33; 8.1±4.4 years) of 7.1±2.7 kPa, and the biliary atresia group (n=19; 0.2±0.1 years) of 19.7±15.2 kPa. Liver stiffness measurements differed across METAVIR fibrosis categories in all disease groups. The highest values were found in biliary atresia, at fibrosis stages ≥F2 (F2: 12.4±1.6 kPa, F3: 17.8±2 kPa, F4: 41.5±12.4 kPa). Liver stiffness was strongly associated only with fibrosis (P<0.0001) in various chronic liver diseases, but with necroinflammatory activity (P<0.0001) and fibrosis (P=0.002) in autoimmune hepatitis, and with age (P<0.0001), fibrosis (P<0.0001) and cholestasis (P=0.009) in biliary atresia. Optimal cutoffs for detecting advanced fibrosis (≥F3) were 16 kPa (area under curve: 0.98; sensitivity: 87.5%; specificity: 96.7%) in biliary atresia and 8.7 kPa (area under curve: 0.98; sensitivity: 93.8%; specificity: 96.1%) in other chronic liver diseases. CONCLUSION Two-dimensional shear wave elastography is reliable in assessing liver fibrosis in children with chronic liver diseases.
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Affiliation(s)
- Paraskevi Galina
- Department of Radiology, Aghia Sofia General Children's Hospital, Thivon St. & Papadiamantopoulou St., Goudi, 115 27, Athens, Greece. .,2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
| | - Efthymia Alexopoulou
- 2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Mentessidou
- Department of Pediatric Surgery, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Petros Mirilas
- Department of Pediatric Surgery, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Aglaia Zellos
- 1st Department of Pediatrics, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Lilia Lykopoulou
- 1st Department of Pediatrics, Aghia Sofia General Children's Hospital, Athens, Greece
| | - Amalia Patereli
- Department of Pathology, Aghia Sofia General Children's Hospital, Athens, Greece
| | | | - Nikolaos L Kelekis
- 2nd Department of Radiology, General University Hospital Attikon, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Zarifi
- Department of Radiology, Aghia Sofia General Children's Hospital, Thivon St. & Papadiamantopoulou St., Goudi, 115 27, Athens, Greece
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Florea M, Serban T, Tirpe GR, Tirpe A, Lupsor-Platon M. Noninvasive Assessment of Hepatitis C Virus Infected Patients Using Vibration-Controlled Transient Elastography. J Clin Med 2021; 10:jcm10122575. [PMID: 34200885 PMCID: PMC8230562 DOI: 10.3390/jcm10122575] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/06/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods.
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Affiliation(s)
- Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - George Razvan Tirpe
- Department of Radiology and Medical Imaging, County Emergency Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400000 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Monica Lupsor-Platon
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Correspondence:
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48
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Li X, Xing Y, Zhou D, Xiao H, Zhou Z, Han Z, Sun X, Li S, Zhang L, Li Z, Zhang P, Zhang J, Zhang N, Cao X, Zao X, Du H, Tong G, Chi X, Gao Y, Ye Y. A Non-invasive Model for Predicting Liver Inflammation in Chronic Hepatitis B Patients With Normal Serum Alanine Aminotransferase Levels. Front Med (Lausanne) 2021; 8:688091. [PMID: 34150818 PMCID: PMC8213212 DOI: 10.3389/fmed.2021.688091] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/10/2021] [Indexed: 12/20/2022] Open
Abstract
Background and Aims: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are at risk of disease progression. Currently, liver biopsy is suggested to identify this population. We aimed to establish a non-invasive diagnostic model to identify patients with significant liver inflammation. Method: A total of 504 CHB patients who had undergone liver biopsy with normal ALT levels were randomized into a training set (n = 310) and a validation set (n = 194). Independent variables were analyzed by stepwise logistic regression analysis. After the predictive model for diagnosing significant inflammation (Scheuer's system, G ≥ 2) was established, a nomogram was generated. Discrimination and calibration aspects of the model were measured using the area under the receiver operating characteristic curve (AUC) and assessment of a calibration curve. Clinical significance was evaluated by decision curve analysis (DCA). Result: The model was composed of 4 variables: aspartate aminotransferase (AST) levels, γ-glutamyl transpeptidase (GGT) levels, hepatitis B surface antigen (HBsAg) levels, and platelet (PLT) counts. Good discrimination and calibration of the model were observed in the training and validation sets (AUC = 0.87 and 0.86, respectively). The best cutoff point for the model was 0.12, where the specificity was 83.43%, the sensitivity was 77.42%, and the positive likelihood and negative likelihood ratios were 4.67 and 0.27, respectively. The model's predictive capability was superior to that of each single indicator. Conclusion: This study provides a non-invasive approach for predicting significant liver inflammation in CHB patients with normal ALT. Nomograms may help to identify target patients to allow timely initiation of antiviral treatment.
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Affiliation(s)
- Xiaoke Li
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
| | - Yufeng Xing
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Daqiao Zhou
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Huanming Xiao
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Zhenhua Zhou
- Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhiyi Han
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Xuehua Sun
- Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shuo Li
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ludan Zhang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zhiguo Li
- Department of Gastroenterology, Beijing Fengtai Hospital of Integrated Traditional and Western Medicine, Beijing, China
| | - Peng Zhang
- Department of Gastroenterology and Hepatology, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
| | - Jiaxin Zhang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ningyi Zhang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xu Cao
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaobin Zao
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
| | - Hongbo Du
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
| | - Guangdong Tong
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Xiaoling Chi
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Yueqiu Gao
- Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yong'an Ye
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.,Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
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Nandi N, Fraquelli M. The role of elastography in viral hepatitis and autoimmune hepatitis. Minerva Gastroenterol (Torino) 2021; 67:141-150. [PMID: 34027931 DOI: 10.23736/s2724-5985.21.02788-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The prognosis of chronic liver diseases, which represent a major public health problem, is mainly linked to the extent and progression of liver fibrosis and the subsequent risk of developing cirrhosis and related complications, mainly hepatocellular carcinoma. During the past decade many noninvasive methods and in particular electrographic techniques, have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility and poor acceptance by patients. The aim of this review was to provide a comprehensive review of the role of elastography techniques in viral chronic liver diseases and autoimmune hepatitis, with the focus on the possible advantages and limitations of these techniques and on their diagnostic accuracy in predicting the stage of liver fibrosis.
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Affiliation(s)
- Nicoletta Nandi
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Mirella Fraquelli
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy -
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50
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Nozaki A, Chuma M, Hara K, Moriya S, Fukuda H, Numata K, Tanaka K, Morimoto M, Sakamaki K, Yamanaka T, Kondo M, Maeda S. Sofosbuvir-based therapies associated with regression of liver fibrosis in patients with hepatitis C virus infection: A prospective observational study. Medicine (Baltimore) 2021; 100:e25110. [PMID: 33761674 PMCID: PMC9281984 DOI: 10.1097/md.0000000000025110] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 02/19/2021] [Indexed: 01/05/2023] Open
Abstract
Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2 cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.
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Affiliation(s)
- Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center
| | - Koji Hara
- Gastroenterological Center, Yokohama City University Medical Center
| | - Satoshi Moriya
- Gastroenterological Center, Yokohama City University Medical Center
| | - Hiroyuki Fukuda
- Gastroenterological Center, Yokohama City University Medical Center
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center
| | - Katsuaki Tanaka
- Gastroenterological Center, Yokohama City University Medical Center
| | - Manabu Morimoto
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | | | - Takeharu Yamanaka
- Department of Biostatistics, School of Medicine, Yokohama City University
| | - Masaaki Kondo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine
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