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Heilani MW, Bolender M, Mücke VT, Schwarzkopf KM, Kubesch-Grün A, Abedin N, Dultz G, Zeuzem S, Welsch C, Friedrich-Rust M, Bojunga J, Herrmann E, Mücke MM. Two-Dimensional and Point Shear-Wave Elastography to Predict Esophageal Varices and Clinically Significant Portal Hypertension in Patients with Chronic Liver Disease. J Clin Med 2024; 13:7719. [PMID: 39768641 PMCID: PMC11676802 DOI: 10.3390/jcm13247719] [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: 10/28/2024] [Revised: 11/28/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of our study was to evaluate two-dimensional (2D) and point (p) SWE to predict the presence of esophageal varices (EV) or clinically significant portal hypertension (CSPH). Methods: This was a retrospective analysis of a prospectively performed cohort study of patients with CLD treated in the outpatient clinic of the Frankfurt University Hospital. PSWE using the Hitachi HI Vision ASCENDUS system and the Siemens ACUSON S2000TM system or 2D-SWE using the Toshiba APLIO500 system were analyzed at baseline and during follow-up to predict EV or surrogate parameters of CSPH. ROC curves were calculated for pooled liver stiffness measurements (LSMs) using a bootstrap approach. A combined model of SWE and platelet count was created and a mixed-effect logistic regression analysis using log-transformed values was performed. Results: Overall, 511 patients with CLD and 919 consecutive LSMs were included and 315 patients (61.6%) had signs of CSPH. 2D-SWE performed best to predict EV and CSPH, and the addition of platelet count to the predictive model significantly increased test results for EV (AUC 0.83, 95%-CI: 0.76-0.89; difference in AUC 0.11, 95%-CI: 0.03-0.19, p = 0.004), but only marginally for CSPH (AUC 0.75, 95%-CI: 0.64-0.85; difference in AUC 0.06, 95%-CI: 0.02-0.14, p = 0.150). LSM > 18.5 and >20 kPa were indicative of CSPH and EV, while LSM < 10 kPa and <11 kPa ruled out CSPH and EV, respectively. Conclusions: Our study found that 2D-SWE in combination with platelet count performed best (in comparison to the other SWE methods) to predict EV or CSPH in patients with CLD. Future prospective trials are needed to validate our results.
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Affiliation(s)
- Myriam W. Heilani
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Max Bolender
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Victoria T. Mücke
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Katharina M. Schwarzkopf
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Alica Kubesch-Grün
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Nada Abedin
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Georg Dultz
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Stefan Zeuzem
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Christoph Welsch
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Mireen Friedrich-Rust
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Jörg Bojunga
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Eva Herrmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany;
| | - Marcus M. Mücke
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
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Ahmed N, Kumari A, Murty RS. FibroScan's evolution: a critical 20-year review. J Ultrasound 2024:10.1007/s40477-024-00971-z. [PMID: 39562432 DOI: 10.1007/s40477-024-00971-z] [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: 09/02/2024] [Accepted: 10/11/2024] [Indexed: 11/21/2024] Open
Abstract
FibroScan, initially designed for assessing cheese maturity, has evolved into a crucial medical tool for liver fibrosis diagnosis. This systematic review explores its development history, functionality, and pros and cons compared to traditional liver biopsy. Precision in various clinical settings is scrutinised, emphasising FibroScan's accuracy in conditions like NAFLD and viral-induced liver disease. The article also delves into its potential in paediatrics, its relevance in monitoring COVID-19-related liver complications, and its role in predicting hepatocellular carcinoma risk, Technical aspects, including transducers, imaging integration, and portability, are examined. Various methods for evaluating liver fibrosis are discussed, highlighting FibroScan's suitability for advanced stages, contrasting with the gold standard of liver biopsy for early stages. The impact of FibroScan on long-term liver conditions is emphasised, focusing on early detection, progression monitoring, reduced invasive biopsies, and hepatocellular carcinoma risk prediction. This systematic review underscores FibroScan's transformative potential in liver disease treatment and predicts ongoing research to enhance early detection, disease monitoring, and explore new clinical applications. Anticipated advances include FibroScan-guided liver biopsy, artificial intelligence data analysis, and point-of-care device development, promising a further revolution in liver disease management. The article concludes with optimistic prospects for FibroScan's future.
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Affiliation(s)
- Nisar Ahmed
- Aditya Pharmacy Collage, Surampalem, Andhra Pradesh, India.
- Jawaharlal Nehru Technological University, Kakinada, India.
| | - Ayushi Kumari
- Aditya Pharmacy Collage, Surampalem, Andhra Pradesh, India
- Jawaharlal Nehru Technological University, Kakinada, India
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Dogan F, Celik M, Cosandal BA, Turac B, Ceylan MR, Dincer NG. Evaluation of liver and spleen stiffness measurement with shear wave elastography in brucellosis. Ir J Med Sci 2024; 193:1521-1526. [PMID: 38055148 DOI: 10.1007/s11845-023-03577-2] [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: 11/06/2023] [Accepted: 11/20/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND Human brucellosis, which is endemic in the eastern region of Turkey, infects the reticulo-endothelial system. Acute brucellosis may cause hepatomegaly or splenomegaly. AIMS The main purpose of this study was to investigate the effectiveness of the point shear wave elastography (pSWE) method in identifying and detecting liver and spleen stiffness in acute brucellosis. METHODS This case-control study included 40 patients with acute brusellosis and 60 healthy individuals as a control group. The demographic data, abdominal ultrasonography (USG) and pSWE results of the patient and control groups were evaluated. Statistical and ROC analyses were performed. RESULTS The liver pSWE value was 3.8395 ± 1.171 kPa in the patient group and 1.6619 ± 0.495 kPa in the control group. The spleen pSWE value was 3.2431 ± 1.803 kPa in the patient group and 1.3793 ± 0.622 kPa in the control group. The mean liver and spleen pSWE values were statistically significantly higher in the patient group than in the control group (p < 0.001). Cut-off values were determined as 2.524 for the liver pSWE and 1.62667 for the spleen pSWE. From the AUC values (0.959, 0.903), the diagnostic performance of liver and spleen pSWE values were seen to be excellent in distinguishing between patient and control groups. CONCLUSIONS The study results showed that liver and spleen stiffness were high in acute brucellosis patients and had predictive significance above certain cut-off values. It can be considered that pSWE, which evaluates liver and spleen stiffness in acute brucellosis, may provide diagnostic benefit as a reliable, non-invasive technique.
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Affiliation(s)
- Ferit Dogan
- Department of Radiology, Harran University, Sanliurfa, 63300, Turkey.
| | - Mehmet Celik
- Department of Radiology, Harran University, Sanliurfa, 63300, Turkey
| | | | - Burak Turac
- Department of Radiology, Harran University, Sanliurfa, 63300, Turkey
| | | | - Nevin Guler Dincer
- Department of Statistics, Faculty of Science, University of Mugla Sıtkı Kocman, Mugla, Turkey
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Mao Y, Ma S, Liu C, Liu X, Su M, Li D, Li Y, Chen G, Chen J, Chen J, Zhao J, Guo X, Tang J, Zhuge Y, Xie Q, Xie W, Lai R, Cai D, Cai Q, Zhi Y, Li X. Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update. Hepatol Int 2024; 18:384-419. [PMID: 38402364 DOI: 10.1007/s12072-023-10633-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 12/18/2023] [Indexed: 02/26/2024]
Abstract
Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.
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Affiliation(s)
- Yimin Mao
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China.
| | - Shiwu Ma
- Department of Infectious Diseases, The 920th Hospital of Chinese PLA Joint Logistics Support Force, Kunming, 650032, Yunnan, China
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiaoyan Liu
- Department of Pharmacy, Huangpu Branch of the 9th People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China
| | - Minghua Su
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Dongliang Li
- Department of Hepatobiliary Medicine, The 900th Hospital of Chinese PLA Joint Logistics Support Force, Fuzhou, 350025, Fujian, China
| | - Yiling Li
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Gongying Chen
- Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, Zhejiang, China
| | - Jun Chen
- Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China
| | - Jinjun Chen
- Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Jingmin Zhao
- Department of Pathology and Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xiaoyan Guo
- Department of Gastroenterology, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China
| | - Jieting Tang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
| | - Yuzheng Zhuge
- Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Wen Xie
- Center of Liver Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100088, China
| | - Rongtao Lai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Qingxian Cai
- Department of Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, 518112, Guangdong, China
| | - Yang Zhi
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
| | - Xiaoyun Li
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, NHC Key Laboratory of Digestive Diseases, Shanghai Research Center of Fatty Liver Disease, Shanghai, 200001, China
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Bosselmann EA, Engel B, Hartleben B, Wedemeyer H, Jaeckel E, Maasoumy B, Potthoff A, Zender S, Taubert R. Prospective comparison of liver stiffness measurement methods in surveillance biopsies after liver transplantation. FRONTIERS IN TRANSPLANTATION 2023; 2:1148195. [PMID: 38993851 PMCID: PMC11235307 DOI: 10.3389/frtra.2023.1148195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 11/03/2023] [Indexed: 07/13/2024]
Abstract
Background Liver stiffness measurements (LSMs) have proven useful for non-invasive detection of fibrosis. Previous studies of LSMs after transplantation were performed in cohorts dominated by hepatitis C reinfections and indication biopsies for the evaluation of graft dysfunction. However, the diagnostic fidelity of LSMs for fibrosis is biased by inflammation e.g., during replicative hepatitis C or rejection. Materials and methods The current study aimed for a head-to-head comparison of two different LSMs, acoustic radiation force impulse (ARFI) and transient elastography (TE), and a determination of cut-off values for the detection of advanced fibrosis (any LAF score component ≥2) in grafts undergoing surveillance biopsies (svLbx) without recurrent hepatitis C. Results 103 svLbx were paired with valid LSMs at time of biopsy. AUROC analyses showed significant positive correlation with fibrosis for both methods (TE: AUROC = 0.819 (p < 0.001; 95%CI: 0.717-0.921); ARFI: AUROC = 0.771 (p = 0.001; 95%CI: 0.652-0.890). Patients were randomly assigned to training and validation cohorts for both LSM methods. Cut-off values were determined at 1.29 m/s (ARFI) and at 7.5 kPa (TE) in training cohorts. Sensitivity and specificity in training and validation cohorts were: TE: SEN 0.818 and 0.5; SPE 0.742 and 0.885; ARFI: SEN 0.818 and 1.0; SPE 0.75 and 0.586. LSMs were not associated with BANFF criteria for relevant graft injury. Conclusion LSM is a good non-invasive tool to screen for advanced graft fibrosis but not for relevant graft injury in patients with (near) normal liver enzymes. Fibrosis cut-off values identified and validated in svLbx were lower than in previous cohorts using indication biopsies.
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Affiliation(s)
- Emily A Bosselmann
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Bastian Engel
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Björn Hartleben
- Institute for Pathology, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Elmar Jaeckel
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Andrej Potthoff
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Steffen Zender
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Richard Taubert
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
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Rabindranath M, Zaya R, Prayitno K, Orchanian-Cheff A, Patel K, Jaeckel E, Bhat M. A Comprehensive Review of Liver Allograft Fibrosis and Steatosis: From Cause to Diagnosis. Transplant Direct 2023; 9:e1547. [PMID: 37854023 PMCID: PMC10581596 DOI: 10.1097/txd.0000000000001547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/11/2023] [Accepted: 09/14/2023] [Indexed: 10/20/2023] Open
Abstract
Despite advances in posttransplant care, long-term outcomes for liver transplant recipients remain unchanged. Approximately 25% of recipients will advance to graft cirrhosis and require retransplantation. Graft fibrosis progresses in the context of de novo or recurrent disease. Recurrent hepatitis C virus infection was previously the most important cause of graft failure but is now curable in the majority of patients. However, with an increasing prevalence of obesity and diabetes and nonalcoholic fatty liver disease as the most rapidly increasing indication for liver transplantation, metabolic dysfunction-associated liver injury is anticipated to become an important cause of graft fibrosis alongside alloimmune hepatitis and alcoholic liver disease. To better understand the landscape of the graft fibrosis literature, we summarize the associated epidemiology, cause, potential mechanisms, diagnosis, and complications. We additionally highlight the need for better noninvasive methods to ameliorate the management of graft fibrosis. Some examples include leveraging the microbiome, genetic, and machine learning methods to address these limitations. Overall, graft fibrosis is routinely seen by transplant clinicians, but it requires a better understanding of its underlying biology and contributors that can help inform diagnostic and therapeutic practices.
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Affiliation(s)
- Madhumitha Rabindranath
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Rita Zaya
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Khairunnadiya Prayitno
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, ON, Canada
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada
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Azhie A, Sharma D, Sheth P, Qazi-Arisar FA, Zaya R, Naghibzadeh M, Duan K, Fischer S, Patel K, Tsien C, Selzner N, Lilly L, Jaeckel E, Xu W, Bhat M. A deep learning framework for personalised dynamic diagnosis of graft fibrosis after liver transplantation: a retrospective, single Canadian centre, longitudinal study. Lancet Digit Health 2023; 5:e458-e466. [PMID: 37210229 DOI: 10.1016/s2589-7500(23)00068-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 03/13/2023] [Accepted: 03/23/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND Recurrent graft fibrosis after liver transplantation can threaten both graft and patient survival. Therefore, early detection of fibrosis is essential to avoid disease progression and the need for retransplantation. Non-invasive blood-based biomarkers of fibrosis are limited by moderate accuracy and high cost. We aimed to evaluate the accuracy of machine learning algorithms in detecting graft fibrosis using longitudinal clinical and laboratory data. METHODS In this retrospective, longitudinal study, we trained machine learning algorithms, including our novel weighted long short-term memory (LSTM) model, to predict the risk of significant fibrosis using follow-up data from 1893 adults who had a liver transplantation between Feb 1, 1987, and Dec 30, 2019, with at least one liver biopsy post transplantation. Liver biopsy samples with indefinitive fibrosis stage and those from patients with multiple transplantations were excluded. Longitudinal clinical variables were collected from transplantation to the date of last available liver biopsy. Deep learning models were trained on 70% of the patients as the training set and 30% of the patients as the test set. The algorithms were also separately tested on longitudinal data from patients in a subgroup of patients (n=149) who had transient elastography within 1 year before or after the date of liver biopsy. Weighted LSTM model performance for diagnosing significant fibrosis was compared against LSTM, other deep learning models (recurrent neural network and temporal convolutional network), and machine learning models (Random Forest, Support vector machines, Logistic regression, Lasso regression, and Ridge regression) and aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and transient elastography. FINDINGS 1893 people who had a liver transplantation (1261 [67%] men and 632 [33%] women) with at least one liver biopsy between Jan 1, 1992, and June 30, 2020, were included in the study (591 [31%] cases and 1302 [69%] controls). The median age at liver transplantation was 53·7 years (IQR 47·3-59·0) for cases and 55·3 years (48·0 to 61·2) for controls. The median time interval between transplant and liver biopsy was 21 months (5 to 71). The weighted LSTM model (area under the curve 0·798 [95% CI 0·790 to 0·810]) consistently outperformed other methods, including unweighted LSTM (0·761 [0·750 to 0·769]; p=0·031) Recurrent Neural Network (0·736 [0·721 to 0·744]), Temporal Convolutional Networks (0·700 [0·662 to 0·747], and Random Forest 0·679 [0·652 to 0·707]), FIB-4 (0·650 [0·636 to 0·663]) and APRI (0·682 [0·671 to 0·694]) when diagnosing F2 or worse stage fibrosis. In a subgroup of patients with transient elastography results, weighted LSTM was not significantly better at detecting fibrosis (≥F2; 0·705 [0·687 to 0·724]) than transient elastography (0·685 [0·662 to 0·704]). The top ten variables predictive for significant fibrosis were recipient age, primary indication for transplantation, donor age, and longitudinal data for creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, platelets, white blood cell count, and weight. INTERPRETATION Deep learning algorithms, particularly weighted LSTM, outperform other routinely used non-invasive modalities and could help with the earlier diagnosis of graft fibrosis using longitudinal clinical and laboratory variables. The list of most important predictive variables for the development of fibrosis will enable clinicians to modify their management accordingly to prevent onset of graft cirrhosis. FUNDING Canadian Institute of Health Research, American Society of Transplantation, Toronto General and Western Hospital Foundation, and Paladin Labs.
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Affiliation(s)
- Amirhossein Azhie
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Divya Sharma
- Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Priya Sheth
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Fakhar Ali Qazi-Arisar
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada; National Institute of Liver & Gastrointestinal Diseases, Dow University of Health Sciences, Karachi, Pakistan
| | - Rita Zaya
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Maryam Naghibzadeh
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada
| | - Kai Duan
- Department of Pathology, University Health Network, Toronto, ON, Canada
| | - Sandra Fischer
- Department of Pathology, University Health Network, Toronto, ON, Canada
| | - Keyur Patel
- Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Cynthia Tsien
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Leslie Lilly
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Wei Xu
- Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Ajmera Transplant Program, University Health Network, Toronto, ON, Canada; Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
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Hinkson A, Lally H, Gibson H, Jones R, Rowe IA, Shinkins B, Parker R. Meta-analysis: Enhanced liver fibrosis test to identify hepatic fibrosis in chronic liver diseases. Aliment Pharmacol Ther 2023; 57:750-762. [PMID: 36650720 DOI: 10.1111/apt.17385] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/06/2022] [Accepted: 12/27/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND & AIMS Patients with liver disease can be stratified for risk of liver-related ill health by degree of hepatic fibrosis. The Enhanced liver fibrosis (ELF) test was developed to quantify hepatic fibrosis non-invasively and is widely used. The objective of this review was to identify and synthesise the evidence on the diagnostic accuracy of the ELF test for staging of hepatic fibrosis. APPROACH & RESULTS Searches of PubMed and EMBASE were conducted between October 2020 and November 2021 to identify studies reporting the diagnostic accuracy of the ELF test compared to histology in liver disease patients. QUADAS-2 was used to assess risk of bias in each study. Meta-analysis using the multiple thresholds model described by Steinhauser S, Schumacher M, Rücker G. Modelling multiple thresholds in meta-analysis of diagnostic test accuracy studies. BMC Med. Res. Methodol. 2016;16. 10.1186/s12874-016-0196-1 allowed synthesis of 2 × 2 data at different cut-offs. Sixty-three studies were included in this review. These studies included 19,285 patients with or at risk of liver disease from viral hepatitis, Non-Alcoholic Fatty Liver Disease, Alcohol-related Liver Disease and other mixed chronic liver diseases. The prevalence of significant fibrosis, advanced fibrosis and cirrhosis was 47.5%, 39.2% and 4.4%, respectively. Cut-offs with maximal Youden index were generated with AUROC = 0.811 (95% CI: 0.736-0.870), 0.812 (95% CI: 0.758-0.856) and 0.810 (95% CI: 0.694-0.888) to detect significant fibrosis, advanced fibrosis or cirrhosis, respectively. Diagnostic accuracy of the ELF test varied between different liver diseases and cut-offs to detect each stage with 95% sensitivity or specificity were also generated. CONCLUSIONS Meta-analysis revealed considerable variability in the ability of ELF to stage fibrosis across disease aetiologies. Research has mostly focused on viral hepatitis and NAFLD. There is currently a lack of data on the value of the ELF test in Alcohol-related liver disease and patients in primary care settings.
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Affiliation(s)
- Alexander Hinkson
- Leeds Liver Unit, St James' University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Liver Research Group, University of Leeds, Leeds, UK.,Leeds Institute for Medical Research, University of Leeds, Leeds, UK
| | - Hannah Lally
- School of Medicine, University of Leeds, Leeds, UK
| | | | - Rebecca Jones
- Leeds Liver Unit, St James' University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Ian A Rowe
- Leeds Liver Unit, St James' University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Liver Research Group, University of Leeds, Leeds, UK.,Leeds Institute for Medical Research, University of Leeds, Leeds, UK
| | - Bethany Shinkins
- Test Evaluation Group, Leeds Institute for Health Sciences, University of Leeds, Leeds, UK
| | - Richard Parker
- Leeds Liver Unit, St James' University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.,Leeds Liver Research Group, University of Leeds, Leeds, UK
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9
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Bou Daher H, Manka P, Syn WK. Settling the Score: Which Fibrosis Screening Tool Is the Most Reliable for Nonalcoholic Fatty Liver Disease? Dig Dis Sci 2023; 68:2217-2220. [PMID: 36947290 DOI: 10.1007/s10620-023-07899-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 02/21/2023] [Indexed: 03/23/2023]
Affiliation(s)
- Halim Bou Daher
- Department of Internal Medicine, Saint Louis University, St Louis, MO, USA.
| | - Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany
| | - Wing-Kin Syn
- Department of Internal Medicine, Saint Louis University, St Louis, MO, USA
- Division of Gastroenterology and Hepatology, Saint Louis University, St Louis, MO, USA
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10
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Mulinacci G, Cristoferi L, Palermo A, Luca M, Gerussi A, Invernizzi P, Carbone M. Risk stratification in primary sclerosing cholangitis. Minerva Gastroenterol (Torino) 2023; 69:84-94. [PMID: 33300753 DOI: 10.23736/s2724-5985.20.02821-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic liver disorder commonly affecting young patients and associated with uncertain prognosis and elevated risk of end-stage liver disease and hepatobiliary cancer. Rate of progression in PSC is heterogeneous and accurately predicting the disease course is of paramount importance to clinical practice and interventional trial design. So far, efforts have brought to the development of models looking at short-to-middle-term outcome using composite models including clinical, laboratory, radiological and histological parameters with limited performance. In the era of whole genome sequencing and digital innovation, the time is ripe for the development of stratified medicine in PSC. Efforts should be directed toward developing well-phenotyped cohorts of patients with longitudinal follow-up across sustained periods of time, application of novel image-processing technology, and biomarker discovery using multiomics platforms.
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Affiliation(s)
- Giacomo Mulinacci
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Laura Cristoferi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Andrea Palermo
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Martina Luca
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Alessio Gerussi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Marco Carbone
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milan Bicocca, Milan, Italy - .,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
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11
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Schambeck JPL, Forte GC, Gonçalves LM, Stuker G, Kotlinski JBF, Tramontin G, Altmayer S, Watte G, Hochhegger B. Diagnostic accuracy of magnetic resonance elastography and point-shear wave elastography for significant hepatic fibrosis screening: Systematic review and meta-analysis. PLoS One 2023; 18:e0271572. [PMID: 36730265 PMCID: PMC9894488 DOI: 10.1371/journal.pone.0271572] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 07/03/2022] [Indexed: 02/03/2023] Open
Abstract
The hepatic diseases are extremely common in clinical practice. The correct classification of liver fibrosis is extremely important, as it influences therapy and predicts disease outcomes. The purpose of this study is to compare the diagnostic performance of point-shear wave elastography (pSWE) and magnetic resonance elastography (MRE) in the hepatic fibrosis diagnostic. A meta-analysis was carried out based on articles published until October 2020. The articles are available at following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scientific Electronic Library Online, LILACS, Scopus, and CINAHL. Diagnostic performances were analyzed per METAVIR F2, using 3.5kPa as target fibrosis. Assessment of the methodological quality of the incorporated papers by the QUADAS-2 tool for pSWE and MRE. A total 2,153 studies articles were evaluated and 44 studies, comprising 6,081 patients with individual data, were included in the meta-analysis: 28 studies for pSWE and 16 studies for MRE. The pooled sensitivity and specificity were 0.86 (95%CI 0.80-0.90) and 0.88 (95%CI 0.85-0.91), respectively, for pSWE, compared with 0.94 (95%CI 0.89-0.97) and 0.95 (95%CI 0.89-0.98) respectively, for MRE. The pooled SROC curve for pSWE shows in the area under the curve (AUC) of 0.93 (95%CI 0.90-0.95), whereas the AUC for MRE was 0.98 (95%CI 0.96-0.99). The diagnostic odds ratio for pSWE and MRE were 41 (95%CI 24-72) and 293 (95%CI 86-1000), respectively. There was statistically significant heterogeneity for pSWE sensitivity (I² = 85.26, P<0.001) and specificity (I² = 89.46, P<0.001). The heterogeneity for MRE also was significant for sensitivity (I² = 73.28, P<0.001) and specificity (I² = 87.24, P<0.001). Therefore, both pSWE and MRE are suitable modalities for assessing liver fibrosis. In addition, MRE is a more accurate imaging technique than pSWE and can be used as alternative to invasive biopsy.
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Affiliation(s)
- João Paulo L. Schambeck
- Post-Graduate Program in Medicine and Health Science, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Departament of Radiology, Hospital São Lucas/Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gabriele C. Forte
- Departament of Radiology, Hospital São Lucas/Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Faculty of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- * E-mail:
| | - Luana M. Gonçalves
- Post-Graduate Program in Medicine and Health Science, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Departament of Radiology, Hospital São Lucas/Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Guilherme Stuker
- Departament of Radiology, Hospital São Lucas/Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - João Bruno F. Kotlinski
- Faculty of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Giacomo Tramontin
- Departament of Radiology, Hospital São Lucas/Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Stephan Altmayer
- Post-Graduate Program in Medicine and Health Science, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Guilherme Watte
- Department of Radiology, Medical Imaging Research Lab, LABIMED, Porto Alegre, Rio Grande do Sul, Brazil
| | - Bruno Hochhegger
- Post-Graduate Program in Medicine and Health Science, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Departament of Radiology, Hospital São Lucas/Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Department of Radiology, Medical Imaging Research Lab, LABIMED, Porto Alegre, Rio Grande do Sul, Brazil
- Department of Diagnostic Methods, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
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12
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Sharma D, Choudhary NS, Dhampalwar S, Saraf N, Duseja A, Gautam D, Soin AS, Sud R. Liver Stiffness Values in Persons with Normal Histology. J Clin Exp Hepatol 2023; 13:10-14. [PMID: 36647399 PMCID: PMC9840077 DOI: 10.1016/j.jceh.2022.10.008] [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: 08/23/2022] [Accepted: 10/23/2022] [Indexed: 11/06/2022] Open
Abstract
Background and aims Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies. Methods All prospective liver donors presenting to Medanta, the Medicity hospital between September 2020 and September 2021 fulfilling the eligibility criteria were included in this study. Results A total of 63 donors (36 females and 27 males) were included in the study, 37 (58.7%) donors had normal liver biopsies, and 26 (41.2%) donors showed the presence of non-alcoholic fatty liver disease. LSM values in the normal liver histology group were 5.01 ± 1.99 kPa by the M probe and 5.34 ± 2.25 kPa by the XL probe. Even though the correlation was weak (r = 0.29, P = 0.03), M probe LSM correlated positively with body mass index. There was a good correlation between the LSM measured by the M probe and the XL probe (r = 0.73, P = <0.001). Conclusions LSM value in the biopsy-proven normal liver histology group was 5.01 ± 1.99 by the M probe and 5.34 ± 2.25 by the XL probe.
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Affiliation(s)
- Deepak Sharma
- Institute of Digestive and Hepatobiliary Sciences, Medanta The Medicity, Gurugram, India
| | - Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Swapnil Dhampalwar
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Dheeraj Gautam
- Department of Pathology, Medanta The Medicity, Gurugram, India
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, Gurugram, India
| | - Randhir Sud
- Institute of Digestive and Hepatobiliary Sciences, Medanta The Medicity, Gurugram, India
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13
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Dhillon JK, Fong MW, Fong TL. Use of liver stiffness measurements in acute decompensated heart failure: new applications of a non-invasive technique. ESC Heart Fail 2022; 9:2800-2807. [PMID: 35821206 DOI: 10.1002/ehf2.14038] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 05/18/2022] [Accepted: 06/08/2022] [Indexed: 11/10/2022] Open
Abstract
Heart failure (HF) is a complex disease associated with multisystem organ failure, recurrent hospital admissions, and increased mortality. Acute decompensated heart failure (ADHF) increases central venous pressure (CVP) with resultant hepatic congestion, and this relationship has prognostic significance. The gold standard method of measuring CVP, right heart catheterization, is invasive and costly, prompting further investigation into more accurate non-invasive assessments in HF patients, including liver elastography. Liver elastography relies on imaging techniques to assess liver stiffness measurements (LSM), with high values equating to increased stiffness. While this was developed to assess fibrosis in liver disease, LSM also reflect increased CVP and hepatic congestion. Multiple studies involving ADHF patients, find that increased LSM are independently predictive of increased cardiac events, all-cause mortality, and worse post-operative outcome after both acute HF exacerbation and left ventricular assist device (LVAD) placement. In this review, we discuss the role of LSM as a surrogate for CVP and their applications in determining prognosis in both the ADHF and LVAD populations.
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Affiliation(s)
- Jaspreet K Dhillon
- Department of Internal Medicine, Los Angeles County University of Southern California Medical Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
| | - Michael W Fong
- Division of Cardiovascular Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
| | - Tse-Ling Fong
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
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14
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Lawitz EJ, Li KW, Nyangau E, Field TJ, Chuang JC, Billin A, Wang L, Wang Y, Huss RS, Chung C, Subramanian GM, Myers RP, Hellerstein MK. Elevated de novo lipogenesis, slow liver triglyceride turnover and clinical correlations in nonalcoholic steatohepatitis patients. J Lipid Res 2022; 63:100250. [PMID: 35835205 PMCID: PMC9424583 DOI: 10.1016/j.jlr.2022.100250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/28/2022] [Accepted: 07/02/2022] [Indexed: 11/19/2022] Open
Abstract
De novo lipogenesis (DNL) converts carbon substrates to lipids. Increased hepatic DNL could contribute to pathogenic liver triglyceride accumulation in nonalcoholic steatohepatitis (NASH) and therefore may be a potential target for pharmacological intervention. Here, we measured hepatic DNL using heavy water in 123 NASH patients with fibrosis or cirrhosis, calculated the turnover of hepatic triglycerides to allow repeat labeling studies and determined the associations of hepatic DNL with metabolic, fibrotic, and imaging markers. We found that hepatic DNL was higher in fibrotic NASH patients [median (IQR), 40.7% contribution to palmitate (32.1, 47.5), n=103] than has been previously reported in healthy volunteers and remained elevated [median (IQR), 36.8% (31.0, 44.5), n=20] in patients with cirrhosis, despite lower liver fat content. We also showed that turnover of intrahepatic triglyceride pools was slow (t½ >10 days). Furthermore, DNL contribution was determined to be independent of liver stiffness by magnetic resonance imaging, but was positively associated with the number of large very low-density lipoprotein (VLDL) particles, the size of VLDL, the lipoprotein insulin resistance score, and levels of ApoB100 (r=0.6, p=0.07), and trended towards negative associations with the fibrosis markers FIB-4, FibroSure and APRI. Finally, we found treatment with the acetyl-CoA carboxylase inhibitor firsocostat reduced hepatic DNL at 4 and 12 weeks, using a correction model for residual label that accounts for hepatic triglyceride turnover. Taken together, these data support an important pathophysiological role for elevated hepatic DNL in NASH, and demonstrate that response to pharmacological agents targeting DNL can be correlated with pre-treatment DNL.
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Affiliation(s)
- Eric J Lawitz
- Texas Liver Institute, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA
| | - Kelvin W Li
- Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, California, USA
| | - Edna Nyangau
- Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, California, USA
| | - Tyler John Field
- Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, California, USA
| | | | | | - Lulu Wang
- Gilead Sciences, Inc., Foster City, Californi, USA
| | - Ya Wang
- Gilead Sciences, Inc., Foster City, Californi, USA
| | - Ryan S Huss
- Gilead Sciences, Inc., Foster City, Californi, USA
| | - Chuhan Chung
- Gilead Sciences, Inc., Foster City, Californi, USA
| | | | | | - Marc K Hellerstein
- Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, California, USA.
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15
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Tajiri H, Suzuki M, Bessho K, Ito Y, Murakami J, Hatori R, Takano T, Miyoshi Y, Brooks S. The role of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in the assessment of fibrosis in children with chronic hepatitis C. Sci Rep 2022; 12:11205. [PMID: 35778417 PMCID: PMC9249794 DOI: 10.1038/s41598-022-14553-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 06/08/2022] [Indexed: 11/28/2022] Open
Abstract
At present, noninvasive fibrosis markers are not available for the assessment of liver fibrosis in children with chronic hepatitis C. Sixty-three children with chronic hepatitis C were included. Changes in Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) levels were evaluated in l3 of 27 treatment-naive patients during the natural course of disease (median 4, range 3–6 years). Changes during treatment were evaluated in 27 of 36 patients for 4 (2–9) years of posttreatment follow-up. There were significant differences in the levels of M2BPGi between control group and HCV F0 group (P = 0.002) and between control group and HCV F1 group (P < 0.001). Receiver operating characteristic curve analysis showed that to discriminate stage F1 fibrosis from F0, the cut-off value was 0.95 for M2BPGi with a sensitivity of 52%, specificity of 90%, and area under the curve of 0.687. A substantial decrease in M2BPGi levels by treatment was shown from 0.98 ± 0.57 at pretreatment to 0.42 ± 0.15 at posttreatment (P < 0.001) in the 27 treated patients. Our study shows new findings that M2BPGi may be useful to predict the presence of a mild degree of fibrosis in children with chronic hepatitis C, and such mild fibrosis may be quickly resolved by treatment.
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Affiliation(s)
- Hitoshi Tajiri
- Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Japan.
| | - Mitsuyoshi Suzuki
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kazuhiko Bessho
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshinori Ito
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Jun Murakami
- Division of Pediatrics and Perinatology, Tottori University Faculty of Medicine, Tottori, Japan
| | - Reiko Hatori
- Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Tomoko Takano
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Yoko Miyoshi
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Stephen Brooks
- Department of Microbiology/Immunology, State University of New York at Buffalo, Buffalo, USA
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16
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Ng CH, Tan DJH, Lim XC, Yong JN, Syn N, Soon GST, Huang DQ, Xiao J, Lim GEH, Lim WH, Tan EXX, Dan YY, Noureddin M, Siddiqui MS, Muthiah MD. A Diagnostic Test Meta-Analysis Evaluating Imaging-Based and Blood Biomarker-Based Assessment Tools for Fibrosis After Liver Transplantation. Liver Transpl 2022; 28:659-669. [PMID: 34714966 DOI: 10.1002/lt.26345] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 01/13/2023]
Abstract
Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta-analysis on diagnostic test accuracy was conducted in a random-effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration-controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8-1.0), 0.9 (CI, 0.8-1.0), and 379.6 (CI, 45.8-1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5-0.9), 0.9 (CI, 0.8-0.9), and 0.9 (CI, 0.8-0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis-4 Index (FIB-4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB-4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood-based NITs, which were shown to be less optimal.
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Affiliation(s)
| | | | | | | | - Nicholas Syn
- Yong Loo Lin School of Medicine, Singapore.,Biostatistics & Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | | | - Daniel Q Huang
- Yong Loo Lin School of Medicine, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | | | - Grace En Hui Lim
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | | | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Yock Young Dan
- Yong Loo Lin School of Medicine, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
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17
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Al-Karaghouli M, Fuentes S, Davyduke T, Ma M, Abraldes JG. Impact of statin treatment on non-invasive tests based predictions of fibrosis in a referral pathway for NAFLD. BMJ Open Gastroenterol 2022; 9:e000798. [PMID: 34992072 PMCID: PMC8739069 DOI: 10.1136/bmjgast-2021-000798] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/28/2021] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE In non-alcoholic fatty liver disease (NAFLD), fibrosis determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NAFLD Fibrosis Score (NFS) and Hepamet, have been proposed as a tool to triage NAFLD patients in primary care (PC). These NITs include AST±ALT in their calculations. Many patients with NAFLD take statins, which can affect AST/ALT, but it is unknown if statin affects NITs fibrosis prediction. METHODS We included 856 patients referred through a standardised pathway from PC with a final diagnosis of NAFLD. 832 had reliable vibration controlled transient elastography (VCTE) measurements. We assessed the effects of statins on the association between NITs and VCTE at different fibrosis thresholds. RESULTS 129 out of 832 patients were taking a statin and 138 additional patients had indication for a statin. For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for body mass index, diabetes and age almost completely abrogated these differences, suggesting that these were related to patient's profile rather to a specific effect of statins. Negative predictive values (NPVs) of FIB-4 <1.3 for VCTE >8, 10, 12 and 16 were, respectively, 89, 94, 96% and 100% in patients on a statin and 92, 95, 98% and 99% in patients not on a statin. Statins had similar impact on Hepamet predictions but did not modify NFS predictions. CONCLUSION In patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value, but this had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3).
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Affiliation(s)
- Mustafa Al-Karaghouli
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Sonia Fuentes
- Family Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - Tracy Davyduke
- Hepatology Triage Clinic, Alberta Health Services, Edmonton, Alberta, Canada
| | - Mang Ma
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
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Lin CW, Tsui PH, Lu CH, Hung YH, Tsai MR, Shieh JY, Weng WC. Quantifying Lower Limb Muscle Stiffness as Ambulation Function Declines in Duchenne Muscular Dystrophy with Acoustic Radiation Force Impulse Shear Wave Elastography. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:2880-2889. [PMID: 34284931 DOI: 10.1016/j.ultrasmedbio.2021.06.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 06/11/2021] [Accepted: 06/16/2021] [Indexed: 06/13/2023]
Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscular disease, but validated imaging tools to quantify muscle microstructure alteration as mobility declines are lacking. We aimed to determine the feasibility of using acoustic radiation force impulse shear-wave elastography (ARFI/SWE) in the quantitative assessment of lower limb muscle stiffness in DMD patients. Shear wave velocities (SWVs) of lower limbs were measured in 39 DMD patients and 36 healthy controls aged 3-20 y. Mean SWV values of the controls and of the DMD patients at different ambulatory stages were compared using analysis of variance with Bonferroni correction. The DMD group had increased lower limb muscle stiffness compared with controls. Stiffness of the tibialis anterior and medial gastrocnemius muscle decreased from ambulatory to early non-ambulatory stages, whereas stiffness of the rectus femoris muscle increased from ambulatory to late non-ambulatory stages. We describe how SWV changes in lower limb muscles have the potential to predict ambulatory decline in DMD.
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Affiliation(s)
- Chia-Wei Lin
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
| | - Po-Hsiang Tsui
- Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Hao Lu
- Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
| | | | - Meng-Ru Tsai
- Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Jeng-Yi Shieh
- Department of Physical Medicine and Rehabilitation, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
| | - Wen-Chin Weng
- Department of Pediatrics, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Pediatric Neurology, National Taiwan University Children's Hospital, Taipei, Taiwan.
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19
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Sharma C, Cococcia S, Ellis N, Parkes J, Rosenberg W. Systematic review: Accuracy of the enhanced liver fibrosis test for diagnosing advanced liver fibrosis and cirrhosis. J Gastroenterol Hepatol 2021; 36:1788-1802. [PMID: 33668077 DOI: 10.1111/jgh.15482] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 02/02/2021] [Accepted: 02/22/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS The rising incidence of chronic liver disease (CLD) has increased the need for early recognition. This systematic review assesses the diagnostic accuracy of the enhanced liver fibrosis (ELF) test in cases of advanced fibrosis and cirrhosis due to multiple etiologies in at-risk populations. METHODS Studies evaluating the ELF accuracy in identifying advanced fibrosis or cirrhosis, defined as METAVIR stage F ≥ 3 and F = 4 or equivalent, in patients with non-alcoholic fatty liver disease (NAFLD), alcohol liver disease (ALD), or viral hepatitis were included. Liver biopsy was used as the reference standard. Medline and Embase databases were searched. The QUADAS-2 tool was used as a framework to assess risk of bias and applicability. The area under the receiver operator curve (AUROC) was extracted as a summary measure of diagnostic accuracy. RESULTS Thirty-six studies were included: 11 hepatitis C, 4 hepatitis B, 9 NAFLD, 2 ALD, and 10 mixed. The ELF test showed good diagnostic performance in detecting advanced fibrosis in patients with viral hepatitis (AUROC 0.69 to 0.98) and excellent performance in NAFLD (AUROC 0.78 to 0.97) and ALD (AUROC from 0.92 to 0.94). There is also evidence of good diagnostic performance for detecting cirrhosis in patients with viral hepatitis (AUROC 0.63 to 0.99), good performance in NAFLD (AUROC 0.85 to 0.92), and excellent performance in patients with ALD (AUROC 0.93 to 0.94). CONCLUSION This systematic review supports the use of the ELF test across a range of CLD as a possible alternative to liver biopsy in selected cases.
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Affiliation(s)
- Chetanya Sharma
- Institute for Liver and Digestive Health, University College London, Division of Medicine and Royal Free London NHS Foundation Trust, London, UK
| | - Sara Cococcia
- Institute for Liver and Digestive Health, University College London, Division of Medicine and Royal Free London NHS Foundation Trust, London, UK.,First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy
| | - Nicola Ellis
- Institute for Liver and Digestive Health, University College London, Division of Medicine and Royal Free London NHS Foundation Trust, London, UK
| | - Julie Parkes
- Department of Public Health and Medical Statistics, Faculty of Medicine, University of Southampton, Southampton, UK
| | - William Rosenberg
- Institute for Liver and Digestive Health, University College London, Division of Medicine and Royal Free London NHS Foundation Trust, London, UK
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20
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Pennisi G, Celsa C, Giammanco A, Spatola F, Petta S. The Relevance of Noninvasive Tools To Assess Fibrosis in Non-Alcoholic Fatty Liver Disease. Curr Pharm Des 2021; 26:3928-3938. [PMID: 32436818 DOI: 10.2174/1381612826666200521133307] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 04/16/2020] [Indexed: 12/15/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver diseases worldwide, involving about 25% of people. NAFLD incorporates a large spectrum of pathological conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and its complications include hepatic decompensation and hepatocellular carcinoma (HCC). This progression occurs, over many years, in an asymptomatic way, until advanced fibrosis appears. Thus, the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis are key issues. To date, the histological assessment of fibrosis with liver biopsy is the gold standard, but obviously, invasiveness is the greater threshold. In addition, rare but potentially life-threatening complications, poor acceptability, sampling variability and cost maybe restrict its use. Furthermore, due to the epidemic of NAFLD worldwide and several limitations of liver biopsy evaluation, noninvasive assessment tools to detect fibrosis in NAFLD patients are needed.
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Affiliation(s)
- Grazia Pennisi
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, Palermo, Italy
| | - Ciro Celsa
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, Palermo, Italy
| | - Antonina Giammanco
- Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialities, University of Palermo, Palermo, Italy
| | - Federica Spatola
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, Palermo, Italy
| | - Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, Palermo, Italy
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21
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Hernandez Roman J, Siddiqui MS. The role of noninvasive biomarkers in diagnosis and risk stratification in nonalcoholic fatty liver disease. Endocrinol Diabetes Metab 2020; 3:e00127. [PMID: 33102796 PMCID: PMC7576290 DOI: 10.1002/edm2.127] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 02/28/2020] [Accepted: 02/29/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronically elevated liver enzymes. Diagnosis and risk stratification of NAFLD remains clinically challenge as patients with NAFLD are either asymptomatic or have nonspecific presenting complaints and may have normal liver enzymes. Nonalcoholic steatohepatitis (NASH), the clinically aggressive variant of NAFLD, is also difficult to differentiate noninvasively, and a liver biopsy is required to definitively diagnose NASH. Thus, the definitive diagnosis and risk stratification of NAFLD is embedded in histological assessment of the liver. Several clinical aides been investigated in an attempt to risk stratify and identify patients noninvasively as doing a liver biopsy in all patients with NAFLD are not feasible. Since these biomarkers are unable to differentiate NASH from non-NASH, they have leveraged biochemical changes within the liver as patients progress to varying degree of hepatic fibrosis to identify patients with moderate fibrosis (fibrosis stage 2 or greater) and advanced fibrosis (fibrosis stage 3 or greater) to help guide the need for additional and more definitive workup. These clinical aides span from by-products of apoptosis to statistical modelling of clinically available data to identify 'at-risk' patients with NAFLD. The current review will focus the diagnostic performance of these noninvasive serum-based biomarkers in NAFLD.
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Affiliation(s)
| | - Mohammad S. Siddiqui
- Division of Gastroenterology, Hepatology and NutritionDepartment of Internal MedicineVirginia Commonwealth University (VCU)RichmondVirginia
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22
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Diagnosis of Acute Rejection of Liver Grafts in Young Children Using Acoustic Radiation Force Impulse Imaging. AJR Am J Roentgenol 2020; 215:1229-1237. [PMID: 32877250 DOI: 10.2214/ajr.19.22057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE. Frequency of acute rejection (AR) after pediatric liver transplant remains high despite progress in immunosuppression. Liver biopsy (LB) is the reference standard for the diagnosis of AR despite its potential for morbidity. The purpose of our study was to evaluate the ability of acoustic radiation force impulse (ARFI) imaging to distinguish AR from other causes of short- and medium-term liver dysfunction and to identify liver transplant cases with normal liver function. MATERIALS AND METHODS. ARFI imaging was used to evaluate shear wave velocity (SWV) after liver transplant in young children. All pediatric liver grafts that had LB and ARFI examination between January 2014 and December 2017 were included in this retrospective study. Results of LB were compared with those of SWV. Collected data included age at biopsy and transplant, sex, weight, height, body mass index, interval between liver transplant and shear wave elastography and LB, kind of graft, type of donor, and diagnosis at transplant. ROC curve analysis was performed to assess the diagnostic performance of SWV. Optimal cutoff of SWV using ARFI imaging in predicting AR was identified using the Youden index. RESULTS. Statistical analysis was performed on 54 children; six of the original 60 were excluded because of confounding alterations or changes in outcome. Median SWV was higher in patients with AR (2.03 m/s; interquartile range [IQR], 1.80-2.45 m/s) compared with those with idiopathic hepatitis (1.33 m/s; IQR, 1.12-1.53 m/s), portal hypertension (1.42 m/s; IQR, 1.32-1.72 m/s), cholangitis (1.56 m/s; IQR, 1.07-1.62 m/s) or normal liver function (1.23 m/s; IQR 1.12-1.29 m/s) at protocol biopsies (all comparisons, p < 0.01). SWV higher than 1.73 m/s was predictive for AR (AUC, 0.966). SWV also showed good diagnostic accuracy in normal liver function (AUC, 0.791). ARFI imaging was not predictive for hepatitis (AUC, 0.402), portal hypertension (AUC, 0.556), or cholangitis (AUC, 0.420). CONCLUSION. ARFI imaging could be routinely used in place of LB in pediatric patients with liver dysfunction after liver transplant, restricting indication and risks of biopsy to selected cases.
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23
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Loomba R, Adams LA. Advances in non-invasive assessment of hepatic fibrosis. Gut 2020; 69:1343-1352. [PMID: 32066623 PMCID: PMC7945956 DOI: 10.1136/gutjnl-2018-317593] [Citation(s) in RCA: 223] [Impact Index Per Article: 44.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 01/27/2020] [Accepted: 01/28/2020] [Indexed: 12/14/2022]
Abstract
Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more 'complex' serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.
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Affiliation(s)
- Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, California, USA
| | - Leon A Adams
- Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia
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24
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Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, Kayali Z, Wong VWS, Greenbloom S, Jayakumar S, Shiffman ML, Freilich B, Lawitz EJ, Gane EJ, Harting E, Xu J, Billin AN, Chung C, Djedjos CS, Subramanian GM, Myers RP, Middleton MS, Rinella M, Noureddin M. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology 2020; 72:58-71. [PMID: 32115759 DOI: 10.1002/hep.31205] [Citation(s) in RCA: 251] [Impact Index Per Article: 50.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 01/06/2020] [Accepted: 02/12/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS We evaluated the safety and efficacy of cilofexor (formerly GS-9674), a small-molecule nonsteroidal agonist of farnesoid X receptor, in patients with nonalcoholic steatohepatitis (NASH). APPROACH AND RESULTS In this double-blind, placebo-controlled, phase 2 trial, 140 patients with noncirrhotic NASH, diagnosed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥8% and liver stiffness ≥2.5 kPa by magnetic resonance elastography (MRE) or historical liver biopsy, were randomized to receive cilofexor 100 mg (n = 56), 30 mg (n = 56), or placebo (n = 28) orally once daily for 24 weeks. MRI-PDFF, liver stiffness by MRE and transient elastography, and serum markers of fibrosis were measured at baseline and week 24. At baseline, median MRI-PDFF was 16.3% and MRE-stiffness was 3.27 kPa. At week 24, patients receiving cilofexor 100 mg had a median relative decrease in MRI-PDFF of -22.7%, compared with an increase of 1.9% in those receiving placebo (P = 0.003); the 30-mg group had a relative decrease of -1.8% (P = 0.17 vs. placebo). Declines in MRI-PDFF of ≥30% were experienced by 39% of patients receiving cilofexor 100 mg (P = 0.011 vs. placebo), 14% of those receiving cilofexor 30 mg (P = 0.87 vs. placebo), and 13% of those receiving placebo. Serum gamma-glutamyltransferase, C4, and primary bile acids decreased significantly at week 24 in both cilofexor treatment groups, whereas significant changes in Enhanced Liver Fibrosis scores and liver stiffness were not observed. Cilofexor was generally well-tolerated. Moderate to severe pruritus was more common in patients receiving cilofexor 100 mg (14%) than in those receiving cilofexor 30 mg (4%) and placebo (4%). CONCLUSIONS Cilofexor for 24 weeks was well-tolerated and provided significant reductions in hepatic steatosis, liver biochemistry, and serum bile acids in patients with NASH. ClinicalTrials.gov No. NCT02854605.
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Affiliation(s)
| | | | | | | | | | | | | | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | | | | | | | | | - Eric J Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX
| | - Edward J Gane
- Liver Unit, Auckland City Hospital, Auckland, New Zealand
| | | | - Jun Xu
- Gilead Sciences, Inc., Foster City, CA
| | | | | | | | | | | | | | - Mary Rinella
- Feinberg School of Medicine, Northwestern University, Chicago, IL
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25
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Maev IV, Kuznetsova EI, Andreev DN, Dicheva DT. [Diagnostic accuracy of predictive indexes of liver fibrosis in patients with chronic hepatitis C]. TERAPEVT ARKH 2020; 92:24-28. [PMID: 32598714 DOI: 10.26442/00403660.2020.02.000261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Indexed: 12/14/2022]
Abstract
AIM Assessment of the diagnostic accuracy of predictive indexes of liver fibrosis for the identification of severe fibrosis and cirrhosis (F3F4) in patients with chronic hepatitis C (CHC). MATERIALS AND METHODS The retrospective design study included 127 patients with chronic hepatitis C (mean age 44.511.1 years). To assess the degree of liver fibrosis, all patients underwent transient elastography using a Fibroscan (EchoSens, France) and predictive indexes of liver fibrosis were calculated (APRI, FIB-4, discriminant Bonacini score). Transient elastography was considered as a reference method for assessing the degree of liver fibrosis for subsequent comparison of results with predictive fibrosis indixes. RESULTS The sensitivity of the APRI index for the identification of severe fibrosis and cirrhosis of the liver (F3F4) was 79%, and specificity was 69%. The FIB-4 index showed greater specificity (86%), but less sensitivity (68%). The sensitivity of the discriminant Bonacini scale was 81%, and the specificity was 77%. The positive predictive value of the APRI index, FIB-4 and the Bonacini scale for the identification of severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C was 66; 78 and 72% respectively, and negative predictive value 82; 78 and 84% respectively. CONCLUSION The results of this study indicate the relatively high diagnostic accuracy of a number of predictive indexes for evaluating liver fibrosis (APRI, FIB-4, discriminant Bonachini scale) in identifying severe fibrosis and cirrhosis of the liver (F3F4) in patients with chronic hepatitis C.
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Affiliation(s)
- I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E I Kuznetsova
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D T Dicheva
- Yevdokimov Moscow State University of Medicine and Dentistry
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26
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Fang C, Lim A, Sidhu PS. Ultrasound-based liver elastography in the assessment of fibrosis. Clin Radiol 2020; 75:822-831. [PMID: 32067699 DOI: 10.1016/j.crad.2020.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 01/10/2020] [Indexed: 02/07/2023]
Abstract
Ultrasound-based elastography has rapidly replaced the need for liver biopsy in most patients with chronic liver disease in recent years. The technique is now widely supported by many manufacturers. This review will introduce various current ultrasound-based elastography techniques, review the physics and scanning techniques, discuss potential cofounding factors as well as summarising the evidence for its use in staging liver fibrosis using shear-wave elastography among different disease aetiologies. Future challenges and directions will be also be discussed.
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Affiliation(s)
- C Fang
- Department of Radiology, King's College Hospital NHS Foundation Trust, London, UK.
| | - A Lim
- Department of Radiology, Imperial College Healthcare NHS Trust, London, UK
| | - P S Sidhu
- Department of Radiology, King's College Hospital NHS Foundation Trust, London, UK
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27
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Patel PJ, Connoley D, Rhodes F, Srivastava A, Rosenberg W. A review of the clinical utility of the Enhanced Liver Fibrosis test in multiple aetiologies of chronic liver disease. Ann Clin Biochem 2020; 57:36-43. [PMID: 31529981 DOI: 10.1177/0004563219879962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The rising incidence of chronic liver disease continues to be an increasing health burden. The morbidity and mortality associated with chronic liver disease typically occur in patients with advanced fibrosis. Hence, early identification of those at-risk is of vital importance to ensure appropriate ongoing management. Currently, tools for appropriate risk stratification remain limited. Increasing awareness of the limitations of liver biopsy has driven research into alternative non-invasive methods of fibrosis assessment including serological markers assessing functional changes. One such biomarker, the Enhanced Liver Fibrosis test, was initially validated in a cohort of 1021 patients with mixed aetiology chronic liver disease and shown to perform well. Since this pathfinder study, it has been independently validated in cohorts of hepatitis C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. In addition to performing well as a diagnostic tool, the Enhanced Liver Fibrosis test has been shown to outperform liver biopsy in prognostic studies and is the only non-invasive marker to do so. However, questions remain regarding the use of this test, particularly regarding the possible effect age and alcohol may have on test scores. This review examines the current literature published in relation to the Enhanced Liver Fibrosis test and its clinical utility and highlights areas requiring further study.
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Affiliation(s)
- Preya Janubhai Patel
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK
| | - Declan Connoley
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK.,Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Freya Rhodes
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK
| | - Ankur Srivastava
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK.,Department of Gastroenterology & Hepatology, Southmead Hospital, North Bristol Trust, Bristol, UK
| | - William Rosenberg
- The Institute for Liver and Digestive Health, UCL Division of Medicine, UCL, London, UK
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28
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Point shear wave elastography predicts fibrosis severity and steatohepatitis in alcohol-related liver disease. Hepatol Int 2019; 14:270-280. [PMID: 31858403 DOI: 10.1007/s12072-019-10009-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 12/03/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Point shear wave elastography (pSWE) is a convenient noninvasive tool for assessing liver fibrosis in chronic liver disease. However, there is little information on the correlation between pSWE and the histological findings of alcohol-related liver disease (ALD). Thus, we investigated the diagnostic performance of pSWE in discriminating the fibrosis stage of patients with ALD. METHODS A total of 251 Korean patients with ALD were prospectively enrolled. The diagnostic performance of pSWE was evaluated on the basis of histological fibrosis severity according to Kleiner/Brunt et al.'s criteria and the Laennec classification. RESULTS Median liver stiffness on pSWE significantly increased as liver fibrosis stage increased (p < 0.001). Liver stiffness measurement proved to be an excellent diagnostic indicator in the evaluation of a ≥ F2 stage (area under the receiver operating characteristics curve [AUROC] 0.93; cutoff > 1.46 m/s), ≥ F3 stage (AUROC 0.90; cutoff > 1.47 m/s), and F4 stage (AUROC 0.91; cutoff > 1.66 m/s). Compared with noninvasive serum fibrosis tests, pSWE had the highest AUROC for predicting ≥ F2, ≥ F3, and = F4 stages and the highest Obuchowski index (0.931 ± 0.007; all p < 0.001). The AUROC for discriminating steatohepatitis from simple steatosis was 0.93 (> 1.49 m/s) and the AUROC for discriminating cirrhosis with steatohepatitis from cirrhosis without steatohepatitis was 0.92 (> 2.52 m/s). CONCLUSION pSWE not only gives an accurate indication of liver fibrosis stage in ALD, but also can allow patients with severe alcoholic steatohepatitis to begin corticosteroid treatment without exposing them to the risks of liver biopsy. CLINICAL TRIAL REGISTRATION Clincialtrials.gov Identifier NCT01943318.
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29
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Da BL, Surana P, Kleiner DE, Heller T, Koh C. The Delta-4 fibrosis score (D4FS): A novel fibrosis score in chronic hepatitis D. Antiviral Res 2019; 174:104691. [PMID: 31837393 DOI: 10.1016/j.antiviral.2019.104691] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 12/04/2019] [Accepted: 12/10/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND Chronic Hepatitis D virus (HDV) infection results in the most severe form of viral hepatitis with a rapid progression to cirrhosis. However, non-invasive fibrosis tests that can accurately predict cirrhosis have not been adequately validated. We aimed to develop a clinically useful non-invasive score that can accurately detect cirrhosis. MATERIAL AND METHODS Patients with chronic HDV diagnosed by liver histology or serum PCR were evaluated. Data regarding demographics, laboratory, imaging, vibration-controlled transient elastography (VCTE), and liver biopsy were collected. The total cohort was randomized into a training and validation cohort. The training cohort was used to develop a novel score, the Delta-4 fibrosis score (D4FS) which was then compared to other non-invasive tests in the validation cohort by area under receiver operating characteristics (AUROC). RESULTS 77 patients with chronic HDV were evaluated: mean age 42.6 (SD:11.1) years, 59.7% male, and 57.1% Asian. The total cohort was then separated into a training (n = 45) and validation (n = 32) cohort with no significant differences in terms of clinical characteristics between the two. From the training cohort, the D4FS was derived from variables of statistical and clinical interest (gamma-glutamyl transpeptidase (GGT), platelet count, alanine aminotransferase (ALT), and liver stiffness measurement (LSM)). The D4FS demonstrated the best AUROC in the validation cohort (0.94) followed by VCTE (0.90), FIB-4 (0.86), APRI (0.81), and AAR (0.71). DISCUSSION The D4FS is a clinically useful non-invasive fibrosis score that can accurately detect cirrhosis in patients with chronic HDV infection. Further studies should be performed to further validate clinical utility.
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Affiliation(s)
- Ben L Da
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Pallavi Surana
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
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Davyduke T, Tandon P, Al-Karaghouli M, Abraldes JG, Ma MM. Impact of Implementing a "FIB-4 First" Strategy on a Pathway for Patients With NAFLD Referred From Primary Care. Hepatol Commun 2019; 3:1322-1333. [PMID: 31592044 PMCID: PMC6771169 DOI: 10.1002/hep4.1411] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 07/07/2019] [Indexed: 01/02/2023] Open
Abstract
Detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is essential for stratifying patients according to the risk of liver‐related morbidity. Noninvasive methods such as vibration‐controlled transient elastography (VCTE) and Fibrosis‐4 index (FIB‐4) have been recommended to identify patients for further assessment. The aim of this study was to assess the potential impact of implementing a “FIB‐4 First” strategy to triage patients entering a NAFLD assessment pathway. The pathway for patients with suspected NAFLD was piloted at a tertiary liver center. Referral criteria were 16‐65 years old, elevated alanine aminotransferase and/or steatosis on imaging, and absence of a previous liver diagnosis. A registered nurse risk‐stratified all patients based on VCTE and FIB‐4 was calculated. Potential alternative diagnoses were excluded with bloodwork. A total of 565 patients underwent risk stratification with VCTE with a 97% success rate. Ten percent had VCTE of at least 8 kPa; 560 patients had FIB‐4 available for analysis and 87% had values less than 1.3. Of those with a FIB‐4 of at least 1.3, 69% had a VCTE less than 8 kPa. Further modeling showed that the presence of diabetes, age, and body mass index had only a moderate impact on the association between FIB‐4 and elastography values if using a FIB‐4 threshold of 1.3. Conclusion: A FIB‐4 threshold of 1.3 was acceptable for excluding the presence of advanced fibrosis (assessed by VCTE). A staged risk‐stratification model using FIB‐4 and VCTE could save up to 87% of further assessments. This model could improve accessibility by moving the initial fibrosis evaluation to the medical home and helping to prioritize patients for further specialized care.
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Affiliation(s)
- Tracy Davyduke
- LiverSafe Clinic, Division of Gastroenterology (Liver Unit) University of Alberta, CEGIIR Edmonton Canada.,Alberta Health Services Edmonton Canada
| | - Puneeta Tandon
- LiverSafe Clinic, Division of Gastroenterology (Liver Unit) University of Alberta, CEGIIR Edmonton Canada
| | - Mustafa Al-Karaghouli
- LiverSafe Clinic, Division of Gastroenterology (Liver Unit) University of Alberta, CEGIIR Edmonton Canada
| | - Juan G Abraldes
- LiverSafe Clinic, Division of Gastroenterology (Liver Unit) University of Alberta, CEGIIR Edmonton Canada
| | - Mang M Ma
- LiverSafe Clinic, Division of Gastroenterology (Liver Unit) University of Alberta, CEGIIR Edmonton Canada
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Boyle M, Anstee QM. Nonalcoholic Fatty Liver Disease. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:523-546. [DOI: 10.1002/9781119211419.ch35] [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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32
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Yoshino K, Taura K, Okuda Y, Ikeno Y, Uemoto Y, Nishio T, Yamamoto G, Tanabe K, Koyama Y, Seo S, Kaido T, Okajima H, Imai T, Tanaka S, Uemoto S. Efficiency of acoustic radiation force impulse imaging for the staging of graft fibrosis after liver transplantation. Hepatol Res 2019; 49:394-403. [PMID: 30471140 DOI: 10.1111/hepr.13289] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/15/2018] [Accepted: 11/19/2018] [Indexed: 02/07/2023]
Abstract
AIM Liver biopsy is the gold standard for assessing liver fibrosis (LF) after liver transplantation (LT), but its invasiveness limits its utility. This study aimed to evaluate the usefulness of liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) imaging to assess LF after LT. METHODS Between September 2013 and January 2017, 278 patients who underwent liver biopsy after LT in Kyoto University Hospital (Kyoto, Japan) were prospectively enrolled. Liver stiffness measurement was carried out using ARFI imaging; its value was expressed as shear wave velocity (Vs) [m/s]. The LF was evaluated according to METAVIR score (F0-F4). The diagnostic performance of Vs for F2≤ and F3≤ was assessed and compared with that of laboratory tests using receiver operating characteristic (ROC) analysis. RESULTS The median Vs values increased according to the progression of LF (F0, 1.18 (0.78-1.92); F1, 1.35 (0.72-3.54); F2, 1.55 (1.05-3.37); F3, 1.84 (1.41-2.97)). The Vs had the highest area under the ROC curve (AUROC) for the prediction of both F2 ≤ and F3 ≤ fibrosis (F2, 0.77; and F3, 0.85). With the cut-off value of Vs >1.31, sensitivity, specificity, positive predictive value, and negative predictive value were 89.4%, 53.3%, 37.3%, and 94.2% in predicting F2≤, respectively. Shear wave velocity diagnosed LF better than any laboratory tests regardless of the type of primary disease. CONCLUSIONS Acoustic radiation force impulse helps to assess graft LF after LT. The high sensitivity suggested that ARFI might reduce the frequency of liver biopsies by detecting patients who are unlikely to have significant fibrosis after LT. (Unique trial no. UMIN R000028296.).
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Affiliation(s)
- Kenji Yoshino
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Yukihiro Okuda
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Yoshinobu Ikeno
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Yusuke Uemoto
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Takahiro Nishio
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Gen Yamamoto
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Kazutaka Tanabe
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Yukinori Koyama
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
| | - Takumi Imai
- Department of Clinical Biostatistics/Clinical Biostatistics Course, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan
| | - Shiro Tanaka
- Department of Clinical Biostatistics/Clinical Biostatistics Course, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine Kyoto University, Kyoto, Japan
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Nan Y, Niu X, Wang R, Zhao S, Fu N, Du J, Wang Y, Wang B, Zhang Y. microRNA-1273g-3p is a useful non-invasive test for the prediction of liver fibrosis in patients with chronic hepatitis C. Exp Ther Med 2019; 17:1817-1824. [PMID: 30783454 PMCID: PMC6364236 DOI: 10.3892/etm.2018.7114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 07/07/2017] [Indexed: 12/12/2022] Open
Abstract
Previous studies using microRNA (miRNA or miR) microarrays have demonstrated that miR-1273g-3p is upregulated in patients with hepatitis C virus (HCV)-associated fibrosis. As miRNAs have been suggested to be promising non-invasive biomarkers, the aim of the present study was to assess whether miR-1273g-3p may be useful as a potential indicator of fibrosis progression in patients with HCV. Liver biopsies were performed on 112 patients with chronic hepatitis C (CHC) and liver stiffness measurements (LSM) were performed using FibroTouch. Liver fibrosis was determined based on Meta-analysis of Histological Data in Viral Hepatitis classification, and the aspartate aminotransferase (AST)-to-platelet count (PLT) ratio index (APRI) and Fibrosis-4 score (FIB-4) were calculated. The diagnostic performance of miR-1273g-3p, LSM, APRI and FIB-4 in predicting fibrosis stage were evaluated and compared by receiver operating characteristic (ROC) analysis. It was demonstrated that miR-1273g-3p levels were significantly positively correlated with the liver fibrosis stage (r=0.657, P<0.001). The results of LSM, APRI and FIB-4, the three non-invasive diagnostic methods, had good consistency with liver biopsy results, and their correlation coefficients with fibrosis staging were 0.815, 0.417 and 0.522, respectively. The areas under the ROC curves of miR-1273g-3p for F≥2 and F=4 stage samples were 0.841 and 0.933, respectively, which were lower than LSM (0.890 and 0.937), and higher than FIB-4 (0.791 and 0.766) and APRI (0.719 and 0.760). Spearman analysis demonstrated that serum miR-1273g-3p levels were significantly positively correlated with age, body mass index, alanine aminotransferase, AST and total bilirubin (all P<0.05), and negatively correlated with PLT (P<0.05). However, no significant correlation was observed between miR-1273g-3p levels, baseline HCV RNA loads and genotype. Therefore, the results demonstrated that miR-1273g-3p levels, as a novel non-invasive test, may be a useful and easy method for predicting the stage of liver fibrosis in patients with CHC, and has a better diagnostic performance than FIB-4 and APRI. Further prospective studies are required to validate the efficacy of miR-1273g-3p as a predictor of liver fibrosis.
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Affiliation(s)
- Yuemin Nan
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
- Correspondence to: Professor Yuemin Nan, Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, P.R. China, E-mail:
| | - Xuemin Niu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Rongqi Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Suxian Zhao
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Na Fu
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Jinghua Du
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yang Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Baoyu Wang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
| | - Yuguo Zhang
- Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
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Abdelhaleem H, Gamal Eldeen H, Nabeel MM, Abdelmoniem R, Elakel W, Zayed N, Abdellatif Z, Monir B, Abdelaziz MS, Mogawer S, Elamir M, Elshazli M, Salah A, Hosny A, Yosry A. Evaluation of acoustic radiation force impulse (ARFI) elastography as non-invasive diagnostic tool in living donor liver transplantation. Abdom Radiol (NY) 2019; 44:464-472. [PMID: 30171294 DOI: 10.1007/s00261-018-1732-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Role of acoustic radiation force impulse (ARFI) elastography, in transplant setting, is not well established. We aimed to define the normal mean values of the liver stiffness by ARFI Elastography in healthy liver donors and to evaluate ARFI elastography as predictor of graft fibrosis post living donor liver transplant (LDLT) in comparison to other non-invasive methods (transient elastography [TE], APRI and FIB4). PATIENTS AND METHODS A total of 100 subjects (70 recipients and 30 donors) were recruited. APRI and FIB4 scores were calculated for all recipients. TE and ARFI elastography (Siemens Acuson S2000 Ultrasound System, Germany) were performed to all subjects. All donors and only 30 recipients had liver biopsy. Significant fibrosis was defined as ≥ F2. RESULTS The mean ARFI velocity among the donors was 1.05 ± 0.09 m/s. Regarding the recipients: mean age was 49.5 ± 8.49 years, 85.7% males, fibrosis stages < F2 were the most frequent stages by liver biopsy (86.7%) and TE (67.1%). ARFI median was significantly correlated with TE median, APRI and FIB-4 (r = 0.888, p = 0.000; r = 0.62, p = 0.000, and r = 0.585, p = 0.000, respectively). ARFI performed well in discriminating patients with ≥ F2 (AUROC = 0.93, 95% CI 0.86-0.99, p < 0.01) with best cutoff median value of 1.34 m/s (sensitivity 90%, specificity 82%). CONCLUSION ARFI can be used as a reliable method in assessment of significant fibrosis post-LDLT.
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Affiliation(s)
- Hanan Abdelhaleem
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Hadeel Gamal Eldeen
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt.
| | - Mohammed Mahmoud Nabeel
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Reham Abdelmoniem
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Wafaa Elakel
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Naglaa Zayed
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Zeinab Abdellatif
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Bahaa Monir
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Said Abdelaziz
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
| | - Sherif Mogawer
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mona Elamir
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery and Liver Transplantation, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ayman Salah
- Department of Surgery and Liver Transplantation, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Adel Hosny
- Department of Surgery and Liver Transplantation, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ayman Yosry
- Department of Endemic Medicine and Liver Unit, Faculty of Medicine, Kasr Al-Aini Hospital, Cairo University, Cairo, 11562, Egypt
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35
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Lawitz EJ, Coste A, Poordad F, Alkhouri N, Loo N, McColgan BJ, Tarrant JM, Nguyen T, Han L, Chung C, Ray AS, McHutchison JG, Subramanian GM, Myers RP, Middleton MS, Sirlin C, Loomba R, Nyangau E, Fitch M, Li K, Hellerstein M. Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol 2018; 16:1983-1991.e3. [PMID: 29705265 DOI: 10.1016/j.cgh.2018.04.042] [Citation(s) in RCA: 164] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/15/2018] [Accepted: 04/17/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Increased de novo lipogenesis (DNL) contributes to the pathogenesis of nonalcoholic steatohepatitis (NASH). Acetyl-CoA carboxylase catalyzes the rate-limiting step in DNL. We evaluated the safety and efficacy of GS-0976, a small molecule inhibitor of acetyl-CoA carboxylase, in patients with NASH. METHODS In an open-label prospective study, patients with NASH (n = 10) received GS-0976 20 mg orally once daily for 12 weeks. NASH was diagnosed based on a proton density fat fraction estimated by magnetic resonance imaging (MRI-PDFF) ≥10% and liver stiffness by magnetic resonance elastography (MRE) ≥2.88 kPa. The contribution from hepatic DNL to plasma palmitate was measured by 14 days of heavy water labeling before and at the end of treatment. We performed the same labelling protocol in an analysis of healthy volunteers who were not given DNL (controls, n = 10). MRI-PDFF and MRE at baseline, and at weeks 4 and 12 of GS-0976 administration, were measured. We analyzed markers of liver injury and serum markers of fibrosis. RESULTS The contribution of hepatic DNL to plasma palmitate was significantly greater in patients with NASH compared with controls (43% vs 18%) (P = .003). After 12 weeks administration of GS-0976, the median hepatic DNL was reduced 22% from baseline in patients with NASH (P = .004). Compared with baseline, reductions in MRI-PDFF at week 12 (15.7% vs 9.1% at baseline; P = .006), liver stiffness by MRE (3.4 kPa vs 3.1 kPa at baseline; P = .049), TIMP metallopeptidase inhibitor 1 (275 ng/mL vs 244 ng/mL at baseline; P = .049), and serum level of alanine aminotransferase (101 U/L vs 57 U/L at baseline; P = .23) were consistent with decreased hepatic lipid content and liver injury. At week 12, 7 patients (70%) had a ≥30% decrease in MRI-PDFF. CONCLUSION In an open-label study, patients with NASH given GS-0976 for 12 weeks had reduced hepatic DNL, steatosis, and markers of liver injury. ClinicalTrials.gov no: NCT02856555.
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Affiliation(s)
- Eric J Lawitz
- Texas Liver Institute and University of Texas Health San Antonio, San Antonio, Texas.
| | - Angie Coste
- Texas Liver Institute and University of Texas Health San Antonio, San Antonio, Texas
| | - Fred Poordad
- Texas Liver Institute and University of Texas Health San Antonio, San Antonio, Texas
| | - Naim Alkhouri
- Texas Liver Institute and University of Texas Health San Antonio, San Antonio, Texas
| | - Nicole Loo
- Texas Liver Institute and University of Texas Health San Antonio, San Antonio, Texas
| | | | | | - Tuan Nguyen
- Gilead Sciences, Inc, Foster City, California
| | - Ling Han
- Gilead Sciences, Inc, Foster City, California
| | | | | | | | | | | | | | - Claude Sirlin
- University of California at San Diego, San Diego, California
| | - Rohit Loomba
- University of California at San Diego, San Diego, California
| | - Edna Nyangau
- University of California Berkeley, Berkeley, California
| | - Mark Fitch
- University of California Berkeley, Berkeley, California
| | - Kelvin Li
- University of California Berkeley, Berkeley, California
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Dhyani M, Xiang F, Li Q, Chen L, Li C, Bhan AK, Anthony B, Grajo JR, Samir AE. Ultrasound Shear Wave Elastography: Variations of Liver Fibrosis Assessment as a Function of Depth, Force and Distance from Central Axis of the Transducer with a Comparison of Different Systems. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2209-2222. [PMID: 30143339 PMCID: PMC6594152 DOI: 10.1016/j.ultrasmedbio.2018.07.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 06/25/2018] [Accepted: 07/05/2018] [Indexed: 05/10/2023]
Abstract
We evaluated variation in fibrosis staging caused by depth, pre-load force and measurement off-axis distance on different ultrasound shear wave elastography (SWE) systems prospectively in 20 patients with diffuse liver disease. Shear wave speed (SWS) was measured with transient elastography, acoustic radiation force impulse (ARFI) and 2-D shear wave elastography (SWE). ARFI and 2-D-SWE measurements were obtained at different depths (3, 5 and 7 cm), with different pre-load forces (4, 7 and 10N and variable) and at 0, 2 and 4cm off the central axis of the transducer. A single, blinded pathologist staged fibrosis using the METAVIR system (F0-F4). Area under the receiver operating characteristic curve was charted to differentiate significant fibrosis (F ≥ 2). Depth was the only factor found to influence ARFI-derived values; no acquisition factors were found to affect 2-D-SWE SWS values. ARFI and 2-D-SWE for diagnosis of significant fibrosis at a depth of 7cm along the central axis had good diagnostic performance (areas under the receiver operating characteristic curve: 0.92 and 0.82, respectively), comparable to that of transient elastography. Further investigation of this finding will likely be of interest.
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Affiliation(s)
- Manish Dhyani
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Feixiang Xiang
- Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
| | - Qian Li
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Luzeng Chen
- Peking University First Hospital Ultrasound Center, Beijing, China
| | - Changtian Li
- Department of Ultrasound, The Southern Building, Chinese PLA General Hospital, Beijing, China
| | - Atul K Bhan
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Brian Anthony
- Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Joseph R Grajo
- Department of Radiology, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Anthony E Samir
- Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA
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Patel P, Hossain F, Horsfall LU, Banh X, Hayward KL, Williams S, Johnson T, Bernard A, Brown NN, Lampe G, Buck L, Saad N, Russell AW, Valery PC, Irvine KM, Clouston AD, Stuart KA, Rosenberg W, Powell EE. A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care. Hepatol Commun 2018; 2:893-905. [PMID: 30094401 PMCID: PMC6078214 DOI: 10.1002/hep4.1208] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 05/11/2018] [Accepted: 05/17/2018] [Indexed: 12/13/2022] Open
Abstract
Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB‐4], or enhanced liver fibrosis [ELF] test) are recommended as first‐line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB‐4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB‐4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06‐1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01‐1.30). Concordant LSM <8.2 kPa and ELF <9.8 and concordant LSM ≥8.2 kPa and ELF ≥9.8 had a high negative predictive value (91.7%) and positive predictive value (95.8%) for excluding and identifying clinically significant fibrosis, respectively. Conclusion: Simple scoring tools alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age impacts the ELF test. Further studies are required to confirm whether combining LSM and ELF may enhance accuracy and confidence in identifying clinically significant fibrosis. (Hepatology Communications 2018; 00:000‐000)
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Affiliation(s)
- PreyaJanubhai Patel
- Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Australia.,Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia
| | | | - Leigh Ula Horsfall
- Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Australia.,Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia
| | - Xuan Banh
- Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia
| | - Kelly Lee Hayward
- Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia
| | | | | | - Anne Bernard
- QFAB Bioinformatics, Institute for Molecular Bioscience, Queensland Bioscience Precinct University of Queensland Brisbane Australia
| | | | - Guy Lampe
- Pathology Queensland Brisbane Australia
| | | | - Nivene Saad
- Department of Radiology Princess Alexandra Hospital Brisbane Australia.,School of Medicine University of Queensland Brisbane Australia
| | - Anthony William Russell
- School of Medicine University of Queensland Brisbane Australia.,Department of Diabetes and Endocrinology Princess Alexandra Hospital Brisbane Australia
| | | | - Katharine Margaret Irvine
- Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia.,Mater Research, Translational Research Institute University of Queensland Brisbane Australia
| | - Andrew Donald Clouston
- Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia
| | - Katherine Anne Stuart
- Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Australia
| | - William Rosenberg
- UCL Institute for Liver and Digestive Health, Division of Medicine UCL and Royal Free London NHS Foundation Trust London United Kingdom
| | - Elizabeth Ellen Powell
- Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane Australia.,Centre for Liver Disease Research, Translational Research Institute, School of Medicine University of Queensland Brisbane Australia
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Nacif LS, Paranagua-Vezozzo DC, Matsuda A, Alves VAF, Carrilho FJ, Farias AQ, D'Albuquerque LC, Andraus W. HIGHER VALUES IN LIVER ELASTOGRAPHY AND MELD SCORE ARE MORTALITY PREDICTORS ON LIVER TRANSPLANT WAITING LIST. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2018; 31:e1360. [PMID: 29947694 PMCID: PMC6050003 DOI: 10.1590/0102-672020180001e1360] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Accepted: 02/01/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND Liver elastography have been reported in hepatocellular carcinoma (HCC) with higher values; however, it is unclear to identify morbimortality risk on liver transplantation waiting list. AIM To assess liver stiffness, ultrasound and clinical findings in cirrhotic patients with and without HCC on screening for liver transplant and compare the morbimortality risk with elastography and MELD score. METHOD Patients with cirrhosis and HCC on screening for liver transplant were enrolled with clinical, radiological and laboratory assessments, and transient elastography. RESULTS 103 patients were included (without HCC n=58 (66%); HCC n=45 (44%). The mean MELD score was 14.7±6.4, the portal hypertension present on 83.9% and the mean transient elastography value was 32.73±22.5 kPa. The median acoustic radiation force impulse value of liver parenchyma was 1.98 (0.65-3.2) m/s and 2.16 (0.59-2.8) m/s in HCC group. The HCC group was significantly associated with HCV infection (OR 26.84; p<0.0001), higher levels of serum alpha-fetoprotein (OR 5.51; p=0.015), clinical portal hypertension (OR 0.25; p=0.032) and similar MELD score (p=0.693). The area under the receiver operating characteristics (AUROC) showed sensitivity and specificity for serum alpha-fetoprotein (cutoff 9.1 ng/ml), transient elastography value (cutoff value 9 kPa), and acoustic radiation force impulse value (cutoff value 2.56 m/s) of 50% and 86%, 92% and 17% and 21% and 92%, respectively. The survival group had a mean transient elastography value of 31.65±22.2 kPa vs. 50.87±20.9 kPa (p=0.098) and higher MELD scores (p=0.035). CONCLUSION Elastography, ultrasound and clinical findings are important non-invasive tools for cirrhosis and HCC on screening for liver transplant. Higher values in liver elastography and MELD scores predict mortality.
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Affiliation(s)
- Lucas Souto Nacif
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
| | - Denise C Paranagua-Vezozzo
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
| | - Alina Matsuda
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
| | | | - Flair J Carrilho
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
| | - Alberto Queiroz Farias
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
| | - Luiz Carneiro D'Albuquerque
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
| | - Wellington Andraus
- Liver and Gastrointestinal Transplant Division, Department of Gastroenterology, School of Medicine, University of São Paulo
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39
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Inoue T, Tsuzuki Y, Iio E, Shinkai N, Matsunami K, Fujiwara K, Matsuura K, Nojiri S, Tanaka Y. Clinical Evaluation of Hepatocarcinogenesis and Outcome Using a Novel Glycobiomarker Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein (WFA +-M2BP) in Chronic Hepatitis C with Advanced Fibrosis. Jpn J Infect Dis 2018; 71:177-183. [PMID: 29491234 DOI: 10.7883/yoken.jjid.2017.459] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This study aimed to assess the association between the serum glycobiomarker Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) for liver fibrosis and outcomes and carcinogenesis of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients with advanced fibrosis. Serum WFA+-M2BP levels were measured in 128 consecutive CHC patients including 49 with HCC histopathologically diagnosed with advanced fibrosis (44 with fibrosis stage F3 and 84 with fibrosis stage F4) in our hospital. The median WFA+-M2BP level was significantly higher in F4 than in F3 patients (6.9 vs. 2.3 cutoff index [COI], respectively; p<0.001). The difference in WFA+-M2BP levels between patients with and without HCC was not significant. The respective 5-/8-yr survival rates of patients without HCC at enrollment with high (≥4 COI, n=39), intermediate (1-4 COI, n=33), and low WFA+-M2BP (<1 COI, n=7) levels were 78%/48%, 100%/82%, and 100%/100%, respectively. The differences in survival rates between groups were significant (p=0.0041). Patients with high WFA+-M2BP levels had a significantly higher incidence of HCC than those with low WFA+-M2BP levels (p=0.0019). Cumulative 5-yr carcinogenesis rates in patients with high, intermediate, and low WFA+-M2BP levels were 48.7%, 16.9%, and 0%, respectively; the differences between groups were significant (p=0.002). Serum WFA+-M2BP levels might allow the prediction of carcinogenesis and outcome in CHC patients with advanced fibrosis.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antigens, Neoplasm/blood
- Antigens, Neoplasm/chemistry
- Biomarkers/blood
- Biomarkers/chemistry
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/epidemiology
- Female
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/epidemiology
- Humans
- Liver Cirrhosis/complications
- Liver Cirrhosis/diagnosis
- Liver Cirrhosis/epidemiology
- Liver Neoplasms/complications
- Liver Neoplasms/diagnosis
- Liver Neoplasms/epidemiology
- Male
- Membrane Glycoproteins/blood
- Membrane Glycoproteins/chemistry
- Middle Aged
- Plant Lectins
- Receptors, N-Acetylglucosamine
- Young Adult
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Affiliation(s)
- Takako Inoue
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital
| | - Yuji Tsuzuki
- Clinical Laboratory, Nagoya City University Hospital
| | - Etsuko Iio
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences
| | - Noboru Shinkai
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences
| | - Kayoko Matsunami
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences
| | - Yasuhito Tanaka
- Department of Clinical Laboratory Medicine, Nagoya City University Hospital
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences
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40
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Vinciguerra T, Brunati A, David E, Longo F, Pinon M, Ricceri F, Castellino L, Piga A, Giraudo MT, Tandoi F, Cisarò F, Dell Olio D, Isolato G, Romagnoli R, Salizzoni M, Calvo PL. Transient elastography for non-invasive evaluation of post-transplant liver graft fibrosis in children. Pediatr Transplant 2018; 22. [PMID: 29369488 DOI: 10.1111/petr.13125] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/15/2017] [Indexed: 12/15/2022]
Abstract
As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.
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Affiliation(s)
- Tiziana Vinciguerra
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Andrea Brunati
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Ezio David
- Department of Pathology, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Filomena Longo
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Michele Pinon
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Fulvio Ricceri
- Epidemiology Unit, Regional Health Services ASL TO3, Grugliasco, Italy.,Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Luisa Castellino
- Department of Mathematics "G. Peano", University of Turin, Turin, Italy
| | - Antonio Piga
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | | | - Francesco Tandoi
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Fabio Cisarò
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Dominic Dell Olio
- Regional Transplant Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Giuseppe Isolato
- Institute of Diagnostic and Interventional Radiology, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
| | - Renato Romagnoli
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Mauro Salizzoni
- Liver Transplantation Center, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, University of Turin, Turin, Italy
| | - Pier Luigi Calvo
- Gastroenterologia e Epatologia Pediatrica, Department of Pediatrics, Azienda Ospedaliera-Universitaria Citta`della Salute e della Scienza, Turin, Italy
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Eriksson S, Borsiin H, Öberg CF, Brange H, Mijovic Z, Sturesson C. Perioperative liver and spleen elastography in patients without chronic liver disease. World J Gastrointest Surg 2018; 10:21-27. [PMID: 29492187 PMCID: PMC5827034 DOI: 10.4240/wjgs.v10.i2.21] [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: 11/02/2017] [Revised: 01/14/2018] [Accepted: 02/06/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors.
METHODS Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated.
RESULTS Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s (P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more (P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy (n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin (R2 = 0.154, Pearson’s r = 0.392, P = 0.032) and international normalized ratio (R2 = 0.285, Pearson’s r = 0.534, P = 0.003).
CONCLUSION Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.
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42
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Loomba R, Gindin Y, Jiang Z, Lawitz E, Caldwell S, Djedjos CS, Xu R, Chung C, Myers RP, Subramanian GM, Goodman Z, Charlton M, Afdhal NH, Diehl AM. DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis. JCI Insight 2018; 3:96685. [PMID: 29367468 DOI: 10.1172/jci.insight.96685] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 11/21/2017] [Indexed: 01/04/2023] Open
Abstract
A DNA methylation (DNAm) signature (the "Horvath clock") has been proposed as a measure of human chronological and biological age. We determined peripheral blood DNAm in patients with nonalcoholic steatohepatitis (NASH) and assessed whether accelerated aging occurs in these patients. DNAm signatures were obtained in patients with biopsy-proven NASH and stage 2-3 fibrosis. The DNAm profile from one test and two validation cohorts served as controls. Age acceleration was calculated as the difference between DNAm age and the predicted age based on the linear model derived from controls. Hepatic collagen content was assessed by quantitative morphometry. The Horvath clock accurately predicts the chronological age of the entire cohort. Age acceleration was observed among NASH subjects compared with control data sets and our test controls. Age acceleration in NASH subjects did not differ by fibrosis stage but correlated with hepatic collagen content. A set of 152 differentially methylated CpG islands between NASH subjects and controls identified gene set enrichment for transcription factors and developmental pathways. Patients with NASH exhibit epigenetic age acceleration that correlates with hepatic collagen content.
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Affiliation(s)
- Rohit Loomba
- University of California, San Diego, La Jolla, California, USA
| | | | | | - Eric Lawitz
- Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA
| | | | | | - Ren Xu
- Gilead Sciences Inc., Foster City, California, USA
| | - Chuhan Chung
- Gilead Sciences Inc., Foster City, California, USA
| | | | | | | | | | - Nezam H Afdhal
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Anna Mae Diehl
- Duke Clinical Research Institute, Durham, North Carolina, USA
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43
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López JJ, Pérez-Àlvarez N, Rodríguez RV, Jou A, Carbonell P, Jiménez JA, Soldevila L, Tenesa M, Tor J, Clotet B, Bechini J, Tural C. Optimal Use of Transient Elastography and Acoustic Radiation Force Impulse to Stage Liver Fibrosis in HIV/HCV-Coinfected Patients in Clinical Practice. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2018; 37:113-121. [PMID: 28715086 DOI: 10.1002/jum.14312] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 03/17/2017] [Accepted: 03/22/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES Liver fibrosis (LF) is crucial for the individualized management of patients with hepatitis C virus (HCV). We evaluated the concordance between two noninvasive methods for staging LF, transient elastography (TE) and acoustic radiation force impulse (ARFI), in patients coinfected with human immunodeficiency virus and HCV. We propose an algorithm for optimal use of both techniques in routine clinical practice. METHODS A total of 89 human immunodeficiency virus/HCV-coinfected patients underwent TE and ARFI on the same day. The kappa index was used to assess concordance between the techniques. An algorithm combining ARFI and TE was proposed based on the independent factors associated with a kappa index greater than or equal to 0.70, obtained from a multiple regression analysis. We performed a cost-effectiveness analysis. The study was approved by our institutional review board and all patients signed the informed consent. RESULTS Concordance between TE and ARFI for F2, F3, and F4 was 0.55, 0.59, and 0.69, respectively. Ultrasound normal spleen size (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.05-0.91) and high viral load (OR, 0.36; 95% CI, 0.17-0.77) reduced the probability of agreement between TE and ARFI, whereas ultrasound normal left liver lobe size (OR, 3.32; 95% CI, 1.21-9.10) increased this probability. The algorithm revealed that LF was adequately assessed in 74.16%, with 25.84% of patients misclassified. The incremental cost-effectiveness ratio of TE compared with ARFI to increase concordance by 1% was €8.86. CONCLUSIONS Concordance between TE and ARFI was moderate. In the algorithm we proposed, ARFI was cost-effective as a first technique for the staging of LF in the study population.
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Affiliation(s)
- Juan José López
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Núria Pérez-Àlvarez
- Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Barcelona, Spain
| | - Raul V Rodríguez
- Radiology Service, University Hospital Germans Trias i Pujol, Barcelona, Spain
| | - Antoni Jou
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Pere Carbonell
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - José A Jiménez
- Radiology Service, University Hospital Germans Trias i Pujol, Barcelona, Spain
| | - Laura Soldevila
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Montserrat Tenesa
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jordi Tor
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Bonaventura Clotet
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
- Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Barcelona, Spain
- Irsicaixa Laboratory, University Hospital Germans Trias i Pujol, Barcelona, Spain
- Universitat de Vic, Vic, Spain
| | - Jordi Bechini
- Radiology Service, University Hospital Germans Trias i Pujol, Barcelona, Spain
| | - Cristina Tural
- Internal Medicine Department, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
- Fundació de la LLuita contra la Sida, HIV Clinical Unit, University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain
- Universitat de Vic, Vic, Spain
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44
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Newsome PN, Cramb R, Davison SM, Dillon JF, Foulerton M, Godfrey EM, Hall R, Harrower U, Hudson M, Langford A, Mackie A, Mitchell-Thain R, Sennett K, Sheron NC, Verne J, Walmsley M, Yeoman A. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67:6-19. [PMID: 29122851 PMCID: PMC5754852 DOI: 10.1136/gutjnl-2017-314924] [Citation(s) in RCA: 332] [Impact Index Per Article: 47.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 10/06/2017] [Accepted: 10/15/2017] [Indexed: 12/13/2022]
Abstract
These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease.
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Affiliation(s)
- Philip N Newsome
- National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Rob Cramb
- National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Suzanne M Davison
- Leeds Children’s Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK
| | | | - Edmund M Godfrey
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | | | - Mark Hudson
- Regional Liver and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK
| | | | | | | | - Karen Sennett
- Killick Street Health Centre, London, UK,NHS Islington Clinical Commissioning Group, London, UK
| | - Nicholas C Sheron
- Clinical and Experimental Science, Faculty of Medicine, University of Southampton, Southampton, UK
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45
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Lee CH, Wan YL, Hsu TH, Huang SF, Yu MC, Lee WC, Tsui PH, Chen YC, Lin CY, Tai DI. Interpretation US Elastography in Chronic Hepatitis B with or without Anti-HBV Therapy. APPLIED SCIENCES 2017; 7:1164. [DOI: 10.3390/app7111164] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Inflammation has significant impacts on liver fibrosis measurement by ultrasound elastography. The interpretation requires further optimization in patients with or without anti-viral therapy. We prospectively enrolled a consecutive series of patients with chronic hepatitis B who received liver histology analysis and acoustic radiation force impulse (ARFI). 146 patients who underwent liver biopsy (50.9%) or tumor resection (49.1%) were enrolled. 34 patients (23.3%) had been receiving anti-hepatitis B therapy of various duration. The areas under the receiver-operating characteristic (AUROC) for the diagnosis of Metavir F4 by mean ARFI was 0.820 in the non-treatment group and 0.796 in the treatment group. The ARFI tended to be not lower (100%) than the corresponding Metavir grading in patients with treatment within 12 months, equal (75%) from 13 to 31 months, and lower (71.4%) after 32 months. We conclude that ARFI is a reliable tool for measurement of liver fibrosis in chronic hepatitis B patients with ALT (alanine aminotransferase) <5x the upper limit of normal. For those patients under anti-HBV therapy, the optimal timing for ARFI analysis will be over 1–2.5 years of nucleos(t)ide analogue therapy. The ARFI measurement after 2.5 years tends to be lower than the corresponding histology grading.
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Affiliation(s)
- Cheng-Han Lee
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taipei 105, Taiwan
| | - Yung-Liang Wan
- Department of Medical imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Department of Medical imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
| | - Tse-Hwa Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taipei 105, Taiwan
| | - Shiu-Feng Huang
- Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei 115, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Wei-Chen Lee
- Department of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Po-Hsiang Tsui
- Department of Medical imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
| | - Yi-Cheng Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taipei 105, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taipei 105, Taiwan
| | - Dar-In Tai
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taipei 105, Taiwan
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Performance of transient elastography and serum fibrosis biomarkers for non-invasive evaluation of recurrent fibrosis after liver transplantation: A meta-analysis. PLoS One 2017; 12:e0185192. [PMID: 28953939 PMCID: PMC5617176 DOI: 10.1371/journal.pone.0185192] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 09/07/2017] [Indexed: 02/06/2023] Open
Abstract
Recurrent fibrosis after liver transplantation (LT) impacts on long-term graft and patient survival. We performed a meta-analysis to compare the accuracy of non-invasive methods to diagnose significant recurrent fibrosis (stage F2-F4) following LT. Studies comparing serum fibrosis biomarkers, namely AST-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), or transient elastography (TE) with liver biopsy in LT recipients were systematically identified through electronic databases. In the meta-analysis, we calculated the weighted pooled odds ratio and used a fixed effect model, as there was no significant heterogeneity between studies. Eight studies were included for APRI, four for FIB-4, and twelve for TE. The mean prevalence of significant liver fibrosis was 37.4%. The summary odds ratio was significantly higher for TE (21.17, 95% CI confidence interval 14.10–31.77, p = 1X10-30) as compared to APRI (9.02, 95% CI 5.79–14.07; p = 1X10-30) and FIB-4 (7.08, 95% CI 4.00–12.55; p = 1.93X10-11). In conclusion, TE performs best to diagnose recurrent fibrosis in LT recipients. APRI and FIB-4 can be used as an estimate of significant fibrosis at centres where TE is not available. Longitudinal assessment of fibrosis by means of these non-invasive tests may reduce the need for liver biopsy.
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A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases. J Clin Gastroenterol 2017; 51:639-649. [PMID: 28692443 DOI: 10.1097/mcg.0000000000000788] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND GOAL International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. STUDY Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). RESULTS OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. CONCLUSIONS Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.
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Lei B, Liu Y, Dong C, Chen X, Zhang X, Diao X, Yang G, Liu J, Yao S, Li H, Yuan J, Li S, Le X, Lin Y, Zeng W. Assessment of liver fibrosis in chronic hepatitis B via multimodal data. Neurocomputing 2017. [DOI: 10.1016/j.neucom.2016.09.128] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Tang Y, Zhao J, Yu H, Wu H, Niu N. Acoustic Radiation Force Impulse and Doppler Ultrasonography: Comprehensive Evaluation of Acute Rejection After Liver Transplantation. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2017; 36:1137-1145. [PMID: 28244127 DOI: 10.7863/ultra.16.05052] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 08/25/2016] [Indexed: 06/06/2023]
Abstract
OBJECTIVES The aim of our study was to evaluate the clinical application of color Doppler flow imaging (CDFI) and acoustic radiation force impulse (ARFI) for the diagnosis of acute rejection after liver transplantation. METHODS B-Mode CDFI and ARFI assessments were performed in 76 patients who underwent biopsy after liver transplantation at our institution, between October 2011 and October 2014. The study group included 56 patients with acute rejection confirmed by biopsy, with 20 patients whose liver function recovered within 1 month of transplantation forming the control group. Anteroposterior diameter of the liver, hemodynamic index (consisting of the portal vein diameter, portal vein flow velocity, and hepatic vein flow waveform), and ARFI shear wave velocity (SWV) were measured. We used logistic regression modeling and receiver operating curve to evaluate between-group differences. RESULTS Compared with the control group, patients with acute rejection exhibited increased anteroposterior diameter (P = .035) and change in hemodynamic index (P = .021), including increased portal vein diameter, decreased portal vein flow, and loss of triphasic waveform of hepatic vein flow. Acoustic radiation force impulse SWV was markedly increased in the acute rejection group (P < .001). The correlation r-value of measured parameters to acute rejection diagnosis was 0.253 for anterioposterior diameters, 0.271 for change in hemodynamic index, and 0.721 for increased SWV. Shear wave velocity and change in the hemodynamic index had diagnostic value, with an area under the receiver operating curve of 0.933. CONCLUSIONS Combining CDFI with ARFI was useful for the diagnosis of acute rejection after liver transplantation.
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Affiliation(s)
- Ying Tang
- Department of Ultrasound, Tianjin First Center Hospital, Tianjin, China
| | - Jingwen Zhao
- Department of Ultrasound, Tianjin First Center Hospital, Tianjin, China
| | - Huimin Yu
- Department of Ultrasound, Tianjin First Center Hospital, Tianjin, China
| | - Hongtao Wu
- Department of Ultrasound, Tianjin First Center Hospital, Tianjin, China
| | - Ningning Niu
- Department of Ultrasound, Tianjin First Center Hospital, Tianjin, China
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Soto M, Sampietro-Colom L, Lasalvia L, Mira A, Jiménez W, Navasa M. Cost-effectiveness of enhanced liver fibrosis test to assess liver fibrosis in chronic hepatitis C virus and alcoholic liver disease patients. World J Gastroenterol 2017; 23:3163-3173. [PMID: 28533673 PMCID: PMC5423053 DOI: 10.3748/wjg.v23.i17.3163] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Revised: 03/03/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess liver fibrosis (LF) in hepatitis C virus (HCV) and alcoholic liver disease (ALD), estimate health outcomes and costs of new noninvasive testing strategies
METHODS A Markov model was developed to simulate LF progression in HCV and ALD for a cohort of 40-year-old men with abnormal levels of transaminases. Three different testing alternatives were studied: a single liver biopsy; annual Enhanced liver fibrosis (ELF™) followed by liver stiffness measurement (LSM) imaging as a confirmation test if the ELF test is positive; and annual ELF test without LSM. The analysis was performed from the perspective of a university hospital in Spain. Clinical data were obtained from published literature. Costs were sourced from administrative databases of the hospital. Deterministic and probabilistic sensitivity analyses were performed.
RESULTS In HCV patients, annual sequential ELF test/LSM and annual ELF test alone prevented respectively 12.9 and 13.3 liver fibrosis-related deaths per 100 persons tested, compared to biopsy. The incremental cost-effectiveness ratios (ICERs) were respectively €13400 and €11500 per quality-adjusted life year (QALY). In ALD, fibrosis-related deaths decreased by 11.7 and 22.1 per 100 persons tested respectively with sequential ELF test/LSM and annual ELF test alone. ICERs were €280 and €190 per QALY, respectively.
CONCLUSION The use of the ELF test with or without a confirmation LSM are cost-effective options compared to a single liver biopsy for testing liver fibrosis in HCV and ALD patients in Spain.
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