|
1
|
Starosta RT, Ferraro LC, de Mattos GP, Teixeira LF, Poswar FDO, Michalczuk M, Álvares-da-Silva MR, Schwartz IVD. Predicting liver fibrosis in Gaucher disease: Investigation of contributors and development of a clinically applicable Gaucher liver fibrosis score. Mol Genet Metab 2025; 144:109010. [PMID: 39788861 DOI: 10.1016/j.ymgme.2025.109010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/22/2024] [Accepted: 12/30/2024] [Indexed: 01/12/2025]
Abstract
Gaucher disease (GD) is a rare genetic disorder with multi-system involvement. Liver fibrosis is a long-term complication of GD, potentially leading to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There are currently no validated clinical tools for the monitoring of liver fibrosis in patients with GD. In this study, we aim at assessing the validity of common fibrosis-predicting scores, developed for other diseases, for the use in GD, using transient elastography as a gold-standard, as well as developing the first GD-specific liver fibrosis predicting score. We enrolled 19 adult patients with GD who had been on treatment for a minimum of 1 year on enzyme replacement therapy or substrate reduction therapy and who had no evidence of any other liver disease except GD or metabolic-associated steatotic liver disease (MASLD), which is a common comorbidity of GD. We analyzed the correlation between liver stiffness and genotype, treatment modality (imiglucerase or other therapies), clinical severity, and clinical laboratory tests. We found that the common liver fibrosis scores APRI, FIB-4, and NFS did not accurately predict liver fibrosis in people with GD. We also found that male sex, the DS3 score, AST, and GGT levels significantly correlated with liver stiffness, and used these to create a simple but accurate fibrosis-predicting score specifically for GD (the "Gaucher liver fibrosis score", or GLFS), with high accuracy (AUC = 0.8571, p = 0.0206). We believe that our new GLFS may be used in clinical practice to help prioritize GD patients for closer monitoring of liver fibrosis.
Collapse
Affiliation(s)
- Rodrigo T Starosta
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
| | | | - Gabriela Ponte de Mattos
- School of Medicine, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | | | - Fabiano de Oliveira Poswar
- Medical Genetics Service, HCPA, UFRGS, Porto Alegre, RS, Brazil; Graduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, RS, Brazil
| | - Matheus Michalczuk
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Service of Gastroenterology, HCPA, UFRGS, Porto Alegre, RS, Brazil
| | - Mário Reis Álvares-da-Silva
- Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Service of Gastroenterology, HCPA, UFRGS, Porto Alegre, RS, Brazil
| | - Ida Vanessa Doederlein Schwartz
- Medical Genetics Service, HCPA, UFRGS, Porto Alegre, RS, Brazil; Graduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre, RS, Brazil; InRaras (National Institute of Science and Technology on Rare Diseases), Brazil
| |
Collapse
|
|
2
|
Armandi A, Merizian T, Werner MM, Coxson HO, Sanavia T, Birolo G, Gashaw I, Ertle J, Michel M, Galle PR, Labenz C, Emrich T, Schattenberg JM. Variability of transient elastography-based spleen stiffness performed at 100 Hz. Eur Radiol Exp 2023; 7:79. [PMID: 38087079 PMCID: PMC10716091 DOI: 10.1186/s41747-023-00393-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 10/11/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Spleen stiffness measurement (SSM) performed by transient elastography at 100 Hz is a novel technology for the evaluation of portal hypertension in advanced chronic liver disease, but technical aspects are lacking. We aimed to evaluate the intraexamination variability of SSM and to determine the best transient elastography protocol for obtaining robust measurements to be used in clinical practice. METHODS We analyzed 253 SSM exams with up to 20 scans for each examination, performed between April 2021 and June 2022. All SSM results were evaluated according to different protocols by dividing data into groups of n measurements (from 2 to 19). Considering as reference the median SSM values across all the 20 measurements, we calculated the distribution of the absolute deviations of each protocol from the reference median. This analysis was repeated 1,000 times by resampling the data. Distributions were also stratified by etiology (chronic liver disease versus clinically significant portal hypertension) and different SSM ranges: < 25 kPa, 25-75, and > 75 kPa. RESULTS Overall, we observed that the spleen stiffness exam had less variability if it exceeded 12 measurements, i.e., absolute deviations ≤ 5 kPa at 95% confidence. For exams with higher SSM values (> 75 kPa), as seen in clinically significant portal hypertension, at least 15 measurements are highly recommendable. CONCLUSIONS Fifteen scans per examination should be considered for each SSM exam performed at 100 Hz to achieve a low intraexamination variability within a reasonable time in clinical practice. RELEVANCE STATEMENT Performing at least 15 scans per examination is recommended for 100 Hz SSM in order to achieve a low intraexamination variability, in particular for values > 75 kPa compatible with clinically significant portal hypertension. KEY POINTS • Spleen stiffness measurement by transient elastography is used for stratification in patients with portal hypertension. • At 100 Hz, this method may have intraexamination variability. • A minimum of 15 scans per examination achieves a low intraexamination variability.
Collapse
Affiliation(s)
- Angelo Armandi
- Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Turin, 10126, Italy
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Talal Merizian
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Merle Marie Werner
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Harvey O Coxson
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach & Ingelheim, Germany
| | - Tiziana Sanavia
- Computational Biomedicine Unit, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Turin, 10126, Italy
| | - Giovanni Birolo
- Computational Biomedicine Unit, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, Turin, 10126, Italy
| | - Isabella Gashaw
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach & Ingelheim, Germany
| | - Judith Ertle
- Boehringer Ingelheim International GmbH, Ingelheim, Germany
| | - Maurice Michel
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Peter R Galle
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Christian Labenz
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Tilman Emrich
- Department of Radiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany
| | - Jörn M Schattenberg
- Metabolic Liver Disease Research Program, I. Department of Medicine, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, Mainz, 55131, Germany.
| |
Collapse
|
|
3
|
Ljungquist O, Olinder J, Tverring J, Kjölvmark C, Torisson G. Agreement and reliability of hepatic transient elastography in patients with chronic hepatitis C: A cross-sectional test-retest study. Health Sci Rep 2023; 6:e1184. [PMID: 37021011 PMCID: PMC10069238 DOI: 10.1002/hsr2.1184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/26/2023] [Accepted: 02/16/2023] [Indexed: 04/05/2023] Open
Abstract
Background and Aims Transient elastography (TE) has largely replaced liver biopsy to evaluate fibrosis stage and cirrhosis in chronic hepatitis C. Previous studies have reported excellent reliability of TE but agreement metrics have not been reported. This study aimed to assess interrater agreement and reliability of repeated TE measurements. Methods Two operators performed TE independently, directly after each other. The primary outcome was disagreement, defined as a difference in TE results between operators of ≥33%, as well as the smallest detectable change, SDC95 (i.e., the difference between measurements needed to state with 95% certainty that there is a difference in underlying stiffness). Secondary outcomes included reliability, measured as intraclass correlation (ICC), and patient and examination characteristics associated with the agreement. Results In total, 65 patients were included, with a mean liver stiffness of 9.7 kPa. Of these, 21 (32%) had a disagreement in TE results of ≥33% between the two operators. The SDC95 on the log scale was 1.97, indicating that an almost twofold increase or decrease in liver stiffness would be required to confidently represent a change in the underlying fibrosis. Reliability, estimated using the ICC, was acceptable at 0.86. In a post hoc analysis, fasting less than 5 h before TE was associated with a higher degree of disagreement (48% vs. 19%, p = 0.03). Conclusions In our clinical setting, interrater agreement in directly repeated TE measurements was surprisingly low. It is essential to further investigate the reliability and agreement of TE to determine its validity and usefulness.
Collapse
Affiliation(s)
- Oskar Ljungquist
- Department of Infectious DiseasesHelsingborg HospitalHelsingborgSweden
- Division of Infection Medicine, Department of Clinical SciencesLund UniversityLundSweden
| | - Jon Olinder
- Department of Infectious DiseasesHelsingborg HospitalHelsingborgSweden
- Division of Infection Medicine, Department of Clinical SciencesLund UniversityLundSweden
| | - Jonas Tverring
- Department of Infectious DiseasesHelsingborg HospitalHelsingborgSweden
- Division of Infection Medicine, Department of Clinical SciencesLund UniversityLundSweden
| | | | - Gustav Torisson
- Clinical Infection Medicine, Department of Translational Medicine, Faculty of MedicineLund UniversityMalmöSweden
- Department of Infectious DiseasesSkåne University HospitalMalmöSweden
| |
Collapse
|
|
4
|
Syed T, Chadha N, Kumar D, Gupta G, Sterling RK. Non-Invasive Assessment of Liver Fibrosis and Steatosis in End-Stage Renal Disease Patients Undergoing Renal Transplant Evaluation. Gastroenterology Res 2021; 14:244-251. [PMID: 34527094 PMCID: PMC8425797 DOI: 10.14740/gr1445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/02/2021] [Indexed: 12/19/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) has an increased prevalence in end-stage renal disease (ESRD) due to similar risk factors. The aim of this study was to assess non-invasive testing including transient elastography (TE) for liver stiffness (LS), controlled attenuated parameter (CAP) for steatosis, Fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST) to platelet ratio index (APRI) and NAFLD fibrosis score (NFS), for evaluation of NAFLD along with advanced fibrosis (AF) in patients with ESRD undergoing renal transplant evaluation. Methods Data were retrospectively collected within 12 weeks of TE. Primary outcomes were AF, defined by LS ≥ 9 kPa compared to APRI > 1.5, FIB-4 > 2.67, and NFS of 0.675, and ≥ 5% steatosis by CAP ≥ 263 dB/m compared to liver histology when available. Results A total of 171 patients were evaluated: mean age 56, 65% male, 36% obese, 47% had diabetes, 96% hypertension, and 56% dyslipidemia. Mean LS was 6.5 kPa with 21% having AF. Mean CAP was 232 dB/m, with 25% having steatosis. Those with AF were older with higher NFS. Those with steatosis were obese and had diabetes without higher LS or fibrosis scores. Only NFS was associated with LS ≥ 9 kPa. In those with liver histology, AF was associated with LS ≥ 9 kPa but not with APRI, FIB-4, or NFS. Conclusions Despite normal liver enzymes, non-invasive assessment via TE in ESRD patients exhibited high prevalence of AF and steatosis not detected by APRI or FIB-4 scores. This high prevalence was secondary to the common risk factors such as obesity and diabetes, among patients with NAFLD and ESRD.
Collapse
Affiliation(s)
- Taseen Syed
- Department of Gastroenterology, Nutrition and Hepatology, Virginia Commonwealth University, Richmond, VA, USA.,Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA
| | - Nikita Chadha
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Dhiren Kumar
- Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA.,Department of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
| | - Gaurav Gupta
- Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA.,Department of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
| | - Richard K Sterling
- Department of Gastroenterology, Nutrition and Hepatology, Virginia Commonwealth University, Richmond, VA, USA.,Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA.,Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| |
Collapse
|
|
5
|
Chuah KH, Lai LL, Vethakkan SR, Nik Mustapha NR, Mahadeva S, Chan WK. Liver stiffness measurement in non-alcoholic fatty liver disease: Two is better than one. J Gastroenterol Hepatol 2020; 35:1404-1411. [PMID: 31907981 DOI: 10.1111/jgh.14978] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 12/29/2019] [Accepted: 01/05/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Repeating liver stiffness measurement (LSM) was recently reported to improve accuracy to diagnose fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). There are to date no other studies confirming this finding. This aims to evaluate the accuracy of repeating LSM for the diagnosis of fibrosis stage in NAFLD patients. METHODS Retrospective analysis of prospectively collected data on adult NAFLD patients who had two FibroScan examination within 6 months prior to liver biopsy. F3-F4 fibrosis was excluded using LSM cut-off of 7.9 kPa. RESULTS A total of 136 patients were recruited. Eighty-five percent (115/136) of patients had high baseline LSM (≥ 7.9 kPa). Among them, 25% (29/115) had low repeat LSM (< 7.9 kPa), with only two patients having F3 fibrosis. Forty-eight percent (41/86) of patients with high baseline and repeat LSMs had greater than or equal to F3-F4 fibrosis. All 21 patients with low baseline LSM had F0-F2 fibrosis, except one patient with high repeat LSM who had F3 fibrosis. A strategy of repeating LSM, where only patients with high LSM on both baseline and repeat scans are considered for liver biopsy, will be able to reduce the number of patients being considered for liver biopsy from 85% to 63%. The sensitivity, specificity, positive predictive value, and negative predictive value based on only the baseline scan was 98%, 22%, 37%, and 95%, respectively, while based on the strategy of repeating LSM was 93%, 51%, 48%, and 94%, respectively. CONCLUSION False positive diagnosis of advanced fibrosis in NAFLD patients can be reduced, and unnecessary liver biopsy can be avoided by repeating LSM.
Collapse
Affiliation(s)
- Kee-Huat Chuah
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Lee-Lee Lai
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shireene Ratna Vethakkan
- Endocrinology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Sanjiv Mahadeva
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| |
Collapse
|
|
6
|
Yoo J, Lee JM, Joo I, Yoon JH. Assessment of liver fibrosis using 2-dimensional shear wave elastography: a prospective study of intra- and inter-observer repeatability and comparison with point shear wave elastography. Ultrasonography 2019; 39:52-59. [PMID: 31623416 PMCID: PMC6920625 DOI: 10.14366/usg.19013] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 06/07/2019] [Indexed: 12/18/2022] Open
Abstract
PURPOSE The purpose of this study was to prospectively investigate the intra- and interobserver repeatability of a new 2-dimensional (2D) shear wave elastography (SWE) technique (S-Shearwave Imaging) for assessing liver fibrosis in chronic liver disease patients, and to compare liver stiffness measurements (LSMs) made using 2D-SWE with those made using point SWE (pSWE). METHODS This prospective study received institutional review board approval and informed consent was obtained from all patients. Fifty-three chronic liver disease patients were randomly allocated to group 1 (for intra-observer repeatability [n=33]) or group 2 (for inter-observer repeatability [n=20]). In group 1, two 2D-SWE sessions and one pSWE sessions were performed by one radiologist. In group 2, one 2D-SWE session and one pSWE session were performed by the aforementioned radiologist, and a second 2D-SWE session was performed by another radiologist. The intraclass correlation coefficient (ICC) was used to assess intra- and interobserver reliability. LSMs obtained using 2D-SWE and pSWE were compared and correlated using the paired t test and Pearson correlation coefficient, respectively. RESULTS LSMs made using 2D-SWE demonstrated excellent intra- and inter-observer repeatability (ICC, 0.997 [95% confidence interval, 0.994 to 0.999]) and 0.995 [0.988 to 0.998], respectively). LSMs made using 2D-SWE were significantly different from those made using pSWE (2.1±0.6 m/sec vs. 1.9±0.6 m/sec, P<0.001), although a significant correlation existed between the 2D-SWE and pSWE LSMs (rho=0.836, P<0.001). CONCLUSION S-Shearwave Imaging demonstrated excellent intra- and inter-observer repeatability, and a strong correlation with pSWE measurements of liver stiffness. However, because of the significant difference between LSMs obtained using 2D-SWE and pSWE, these methods should not be used interchangeably.
Collapse
Affiliation(s)
- Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
7
|
Chow JCL, Wong GLH, Chan AWH, Shu SST, Chan CKM, Leung JKY, Choi PCL, Chim AML, Chan HLY, Wong VWS. Repeating measurements by transient elastography in non-alcoholic fatty liver disease patients with high liver stiffness. J Gastroenterol Hepatol 2019; 34:241-248. [PMID: 29890010 DOI: 10.1111/jgh.14311] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 05/29/2018] [Accepted: 06/01/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM The Baveno VI Consensus recommends repeating examination in patients with high liver stiffness measurement (LSM) by transient elastography to reduce false-positive diagnosis of advanced liver disease. We tested whether repeating transient elastography can increase the overall diagnostic accuracy. METHODS Ninety-seven patients with non-alcoholic fatty liver disease who underwent two FibroScan examinations within 6 months prior to liver biopsy were evaluated. An LSM cut-off of 7.9 kPa was used to exclude F3-4 fibrosis. RESULTS Seventy-eight patients had high LSM at baseline, among whom 27 had low LSM on repeated testing; only four had F3 and none had cirrhosis. In contrast, 31 of 51 patients with high LSM at both examinations had F3-4. Nineteen patients had low LSM at baseline; none of them had F3-4 regardless of the second LSM results. If we took LSM <7.9 kPa at either examination as sufficient to exclude F3-4, the negative predictive value remained high at 91%. The positive predictive value for F3-4 increased from 45% in patients with high LSM at baseline to 61% in those with high LSM at both examinations. Sensitivity analysis using different cut-offs yielded similar results, with 76% of patients with LSM >12 kPa at both examinations having F3-4. CONCLUSIONS Transient elastography is a highly sensitive screening test to exclude F3-4 fibrosis in non-alcoholic fatty liver disease patients. One-third of patients with high LSM may have normal results on repeated examination. By repeating examination in cases with high LSM, one may spare patients from unnecessary liver biopsy.
Collapse
Affiliation(s)
- Jeremy Chak-Lun Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Sally She-Ting Shu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Carmen Ka-Man Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Julie Ka-Yu Leung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Paul Cheung-Lung Choi
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Angel Mei-Ling Chim
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.,State Key laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| |
Collapse
|
|
8
|
Caussy C, Chen J, Alquiraish MH, Cepin S, Nguyen P, Hernandez C, Yin M, Bettencourt R, Cachay ER, Jayakumar S, Fortney L, Hooker J, Sy E, Valasek MA, Rizo E, Richards L, Brenner D, Sirlin CB, Ehman RL, Loomba R. Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients With Nonalcoholic Liver Disease. Clin Gastroenterol Hepatol 2018; 16:1974-1982.e7. [PMID: 29104128 PMCID: PMC6050151 DOI: 10.1016/j.cgh.2017.10.037] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 10/13/2017] [Accepted: 10/28/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques used to detect liver fibrosis in nonalcoholic fatty liver disease. MRE detects fibrosis more accurately than TE, but MRE is more expensive, and the concordance between MRE and TE have not been optimally assessed in obese patients. It is important to determine under which conditions TE and MRE produce the same readings, so that some patients can simply undergo TE evaluation to detect fibrosis. We aimed to assess the association between body mass index (BMI) and discordancy between MRE and TE findings, using liver biopsy as the reference, and validated our findings in a separate cohort. METHODS We performed a cross-sectional study of 119 adults with nonalcoholic fatty liver disease who underwent MRE, TE with M and XL probe, and liver biopsy analysis from October 2011 through January 2017 (training cohort). MRE and TE results were considered to be concordant if they found patients to have the same stage fibrosis as liver biopsy analysis. We validated our findings in 75 adults with nonalcoholic fatty liver disease who underwent contemporaneous MRE, TE, and liver biopsy at a separate institution from March 2010 through May 2013. The primary outcome was rate of discordance between MRE and TE in determining stage of fibrosis (stage 2-4 vs 0-1). Secondary outcomes were the rate of discordance between MRE and TE in determining dichotomized stage of fibrosis (1-4 vs 0, 3-4 vs 0-2, and 4 vs 0-3). RESULTS In the training cohort, there was 43.7% discordance in findings from MRE versus TE. BMI associated significantly with discordance in findings from MRE versus TE (odds ratio, 1.69; 95% confidence interval, 1.15-2.51; P = .008) after multivariable adjustment by age and sex. The findings were confirmed in the validation cohort: there was 45.3% discordance in findings from MRE versus TE. BMI again associated significantly with discordance in findings from MRE versus TE (odds ratio, 1.52; 95% confidence interval, 1.04-2.21; P = .029) after multivariable adjustment by age and sex. CONCLUSIONS We identified and validated BMI as a factor significantly associated with discordance of findings from MRE versus TE in assessment of fibrosis stage. The degree of discordancy increases with BMI.
Collapse
Affiliation(s)
- Cyrielle Caussy
- NAFLD Research Center, Department of Medicine, La Jolla, California,Universite Lyon 1, Hospices Civils de Lyon, Lyon, France
| | - Jun Chen
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | | | - Sandra Cepin
- NAFLD Research Center, Department of Medicine, La Jolla, California
| | - Phirum Nguyen
- NAFLD Research Center, Department of Medicine, La Jolla, California
| | | | - Meng Yin
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
| | | | - Edward R. Cachay
- NAFLD Research Center, Department of Medicine, La Jolla, California,Medicine, University of California, San Diego, La Jolla, California
| | - Saumya Jayakumar
- NAFLD Research Center, Department of Medicine, La Jolla, California,Division of Gastroenterology, Department of Medicine, La Jolla, California
| | - Lynda Fortney
- NAFLD Research Center, Department of Medicine, La Jolla, California
| | - Jonathan Hooker
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California
| | - Ethan Sy
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California
| | - Mark A. Valasek
- Department of Pathology, University of California at San Diego, La Jolla, California
| | - Emily Rizo
- NAFLD Research Center, Department of Medicine, La Jolla, California
| | - Lisa Richards
- NAFLD Research Center, Department of Medicine, La Jolla, California
| | - David Brenner
- NAFLD Research Center, Department of Medicine, La Jolla, California,Division of Gastroenterology, Department of Medicine, La Jolla, California
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, California
| | | | - Rohit Loomba
- NAFLD Research Center, Department of Medicine, University of California at San Diego, La Jolla, California; Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, California; Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, California.
| |
Collapse
|
|
9
|
Turchinovich A, Baranova A, Drapkina O, Tonevitsky A. Cell-Free Circulating Nucleic Acids as Early Biomarkers for NAFLD and NAFLD-Associated Disorders. Front Physiol 2018; 9:1256. [PMID: 30294278 PMCID: PMC6158334 DOI: 10.3389/fphys.2018.01256] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 08/20/2018] [Indexed: 12/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the worldwide most common cause of chronic liver pathology, which prevalence strongly correlates with the increasing incidence of diabetes, obesity and metabolic syndrome in the general population. Simple steatosis, the earliest NAFLD stage, usually remains asymptomatic, and appropriate changes in the lifestyle, as well as the diet, can reverse the affected liver into the healthy state. The potential of simple steatosis to progress into severe fibrotic stages and to facilitate carcinogenesis necessitates timely NAFLD detection and risk stratification in community-based healthcare settings. Since their initial discovery a decade ago, extracellular circulating miRNAs have been found in all human biological fluids including blood and shown to hold great promises as non-invasive biomarkers. Normally, intracellular miRNAs participate in the regulation of gene expression, but once released by dying/dead cells they remain highly stable in the extracellular environment for prolonged periods. Therefore, circulating miRNA profiles can reflect the ongoing pathogenic processes in body's tissues and organs, and enable highly sensitive non-invasive diagnosis of multiple disorders. A non-urgent character of the NAFLD-related decision-making justifies the use of chronic liver diseases as an excellent test case for examining the practical utility of circulating miRNAs as biomarkers for longitudinal monitoring of human health. In this review, we summarize the state-of-the-art in the field of early diagnosis of NAFLD using circulating blood miRNAs, and stress the necessity of additional experimental validation of their diagnostic potential. We further emphasize on the potential diagnostics promises of other cell-free RNA species found in human biological fluids.
Collapse
Affiliation(s)
- Andrey Turchinovich
- SciBerg e.Kfm, Mannheim, Germany
- Molecular Epidemiology C080, German Cancer Research Center, Heidelberg, Germany
| | - Ancha Baranova
- School of Systems Biology, George Mason University, Fairfax, VA, United States
- Research Center for Medical Genetics, Moscow, Russia
- Atlas Biomed Group, Moscow, Russia
| | - Oksana Drapkina
- Federal State Institution National Research Center for Preventive Medicine, Moscow, Russia
| | - Alexander Tonevitsky
- Department of Cell Biology, Higher School of Economics, Moscow, Russia
- art photonics GmbH, Berlin, Germany
- SRC Bioclinicum, Moscow, Russia
| |
Collapse
|
|
10
|
Cheng HS, Rademaker M. Monitoring methotrexate-induced liver fibrosis in patients with psoriasis: utility of transient elastography. PSORIASIS-TARGETS AND THERAPY 2018; 8:21-29. [PMID: 29785393 PMCID: PMC5953305 DOI: 10.2147/ptt.s141629] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Increasingly, existing evidence indicates that methotrexate-associated liver injury is related to comorbid risk factors such as diabetes, alcoholism, and obesity, rather than to methotrexate itself. Despite this fact, significant effort continues to be expended in the monitoring of low-dose methotrexate in patients with psoriasis. The gold standard investigation has been liver biopsy, but this is associated with significant morbidity and mortality. As methotrexate-induced liver injury is uncommon, the risk/benefit ratio of liver biopsy has been questioned. Fortunately, a number of new technologies have been developed for the diagnosis of chronic liver disease, including transient elastography (TE). TE is a type of shear wave ultrasound elastography, which measures the speed of shear waves used to estimate hepatic tissue stiffness. Several meta-analyses show very high pooled sensitivity and specificity for the diagnosis of hepatic cirrhosis (87% and 91%, respectively) in a variety of chronic liver disorders. It has a negative predictive value for cirrhosis of >90% and a positive predictive value of 75%. Recent European guidelines now advocate the use of TE as the first-line test for the assessment of fibrosis in alcohol- or hepatitis-related liver disease, including nonalcoholic fatty liver disease (NAFLD). As the prevalence of obesity and metabolic syndrome, including NAFLD, is significantly elevated in patients with psoriasis, TE may be worth considering as a routine investigation for any patient with psoriasis. Although high-quality studies comparing TE with standard liver biopsy in the monitoring of psoriatics on low-dose methotrexate are lacking, the evidence from multiple small cohort studies and case series demonstrates its effectiveness. A recent Australasian position statement recommends that TE should be considered as a routine investigation for monitoring methotrexate therapy, repeated every 3 years if kPa <7.5 and yearly if kPa >7.5. Liver biopsy should be considered for patients with a kPa >9.5.
Collapse
Affiliation(s)
- Harriet S Cheng
- Dermatology Service, Auckland City Hospital, Auckland, New Zealand
| | - Marius Rademaker
- Waikato Clinical Campus, Auckland University Medical School, Hamilton, New Zealand
| |
Collapse
|
|
11
|
Zelber-Sagi S, Shoham D, Zvibel I, Abu-Abeid S, Shibolet O, Fishman S. Predictors for advanced fibrosis in morbidly obese non-alcoholic fatty liver patients. World J Hepatol 2017; 9:91-98. [PMID: 28144390 PMCID: PMC5241533 DOI: 10.4254/wjh.v9.i2.91] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/21/2016] [Accepted: 11/17/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate predictors for fibrosis specifically in a high risk population of morbidly obese patients, including detailed evaluation of lifestyle.
METHODS We conducted a cross-sectional study among morbidly obese patients attending the bariatric clinic at the Tel-Aviv Medical Center between the years 2013-2014 with body mass index (BMI) above 40 or above 35 with co-morbidity. Patients with serum hepatitis B surface antigen or anti-hepatitis C virus antibodies, genetic liver diseases, autoimmune disease or high alcohol intake (≥ 30 g/d in men or ≥ 20 g/d in women) were excluded from the study. Liver fibrosis was estimated by transient elastography (FibroScan®), using the ‘‘XL’’ probe. We collected data on age and gender, education, smoking status and amount, medical history, nutrition and lifestyle habits. All these data were collected using structured and validated questionnaires. Fasting blood test were available for a subsample.
RESULTS Fibroscan was performed on a total of 91 patients, of which 77 had a valid examination according to the accepted criteria. Of those, 21% had significant fibrosis (F2) and 39% had advanced or severe fibrosis (F3 or F4). In multivariate analysis, male gender and BMI had a positive association with advanced fibrosis; the OR for fibrosis F ≥ 2 was 7.93 (95%CI: 2.36-26.64, P = 0.001) for male gender and 1.33 (1.11-1.60 kg/m2, P = 0.002) for BMI. The OR for fibrosis F ≥ 3 was 2.92 (1.08-7.91, P = 0.035) for male gender and 1.17 (1.03-1.33, P = 0.018) for BMI. Subjects were categorized to subgroups based on the combination of male gender and BMI of 40 and above. A significant dose response association with stiffness level was noted across these categories, with the highest stiffness among men with a higher BMI (P = 0.001). In addition, a significant positive correlation between pack-years cigarette smoking and liver stiffness was demonstrated among men (r = 0.54, P = 0.012).
CONCLUSION In the morbidly obese population, a higher BMI, male gender and degree of smoking in men bears a greater risk for advanced nonalcoholic fatty liver disease.
Collapse
|
|
12
|
Extracellular Vesicles: A New Frontier in Biomarker Discovery for Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2016; 17:376. [PMID: 26985892 PMCID: PMC4813235 DOI: 10.3390/ijms17030376] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 03/01/2016] [Accepted: 03/02/2016] [Indexed: 12/14/2022] Open
Abstract
In recent years, the global burden of obesity and diabetes has seen a parallel rise in other metabolic complications, such as non-alcoholic fatty liver disease (NAFLD). This condition, once thought to be a benign accumulation of hepatic fat, is now recognized as a serious and prevalent disorder that is conducive to inflammation and fibrosis. Despite the rising incidence of NAFLD, there is currently no reliable method for its diagnosis or staging besides the highly invasive tissue biopsy. This limitation has resulted in the study of novel circulating markers as potential candidates, one of the most popular being extracellular vesicles (EVs). These submicron membrane-bound structures are secreted from stressed and activated cells, or are formed during apoptosis, and are known to be involved in intercellular communication. The cargo of EVs depends upon the parent cell and has been shown to be changed in disease, as is their abundance in the circulation. The role of EVs in immunity and epigenetic regulation is widely attested, and studies showing a correlation with disease severity have made these structures a favorable target for diagnostic as well as therapeutic purposes. This review will highlight the research that is available on EVs in the context of NAFLD, the current limitations, and projections for their future utility in a clinical setting.
Collapse
|
|
13
|
Tai DI, Tsay PK, Jeng WJ, Weng CC, Huang SF, Huang CH, Lin SM, Chiu CT, Chen WT, Wan YL. Differences in liver fibrosis between patients with chronic hepatitis B and C: evaluation by acoustic radiation force impulse measurements at 2 locations. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2015; 34:813-821. [PMID: 25911714 DOI: 10.7863/ultra.34.5.813] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 08/12/2014] [Indexed: 02/05/2023]
Abstract
OBJECTIVES The purpose of this study was to evaluate liver fibrosis by acoustic radiation force impulse (ARFI) measurements at 2 locations in patients with chronic hepatitis B and C. METHODS A total of 204 consecutive patients (146 male and 58 female) with chronic hepatitis B (n = 121) and C (n = 83) who underwent liver biopsy were enrolled. All patients received ARFI measurements at 2 locations in the right intercostal space on the same day as biopsy. RESULTS There was no difference in median ARFI values between detection locations. However, a significant difference was found for low and high values between locations (median ± SD, 1.38 ± 0.43 versus 1.56 ± 0.55 m/s; P < .001). By receiver operating characteristic (ROC) curve analysis for a METAVIR fibrosis score of F4 (cirrhosis), the lower value of 2 measurements had the highest area under the ROC curve (0.750), followed by the mean value (0.744) and the higher value (0.730). Patients with hepatitis C had a higher area under the ROC curve than patients with hepatitis B (0.824 versus 0.707) for predicting liver cirrhosis. By logistic regression analysis, ARFI was the best modality for predicting liver cirrhosis in hepatitis C, and conventional sonography was the best modality in hepatitis B (P < .001). The ARFI value in patients with hepatitis B was significantly influenced by liver inflammation (P = .019). CONCLUSIONS Acoustic radiation force impulse imaging is the modality of choice for predicting liver cirrhosis in chronic hepatitis C, whereas conventional sonography is still the modality of choice in chronic hepatitis B.
Collapse
Affiliation(s)
- Dar-In Tai
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Pei-Kwei Tsay
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Wen-Juei Jeng
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Chia-Chan Weng
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Shiu-Feng Huang
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Chien-Hao Huang
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Shi-Ming Lin
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Cheng-Tang Chiu
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Wei-Ting Chen
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| | - Yung-Liang Wan
- Departments of Gastroenterology and Hepatology (D.-I.T., W.-J.J., C.-C.W., C.-H.H., S.-M.L., C.-T.C., W.-T.C.) and Medical Imaging and Intervention (Y.-L.W.), Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan, Taiwan (P.-K.T.); Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei, Taiwan (S.-F.H.); and Department of Medical Imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Tao-Yuan, Taiwan (Y.-L.W.)
| |
Collapse
|
|
14
|
Yoon JH, Lee JM, Han JK, Choi BI. Shear wave elastography for liver stiffness measurement in clinical sonographic examinations: evaluation of intraobserver reproducibility, technical failure, and unreliable stiffness measurements. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2014; 33:437-447. [PMID: 24567455 DOI: 10.7863/ultra.33.3.437] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
OBJECTIVES The purpose of this study was to determine the optimal minimum number of liver stiffness measurements on shear wave elastography (SWE) and to evaluate the frequency of technical failures and unreliable stiffness measurements and the intraobserver reproducibility of SWE. METHODS This retrospective study was approved by our Institutional Review Board, and informed consent was waived. From August 2011 to January 2013, 540 patients underwent abdominal sonography, including SWE. In 86 patients (group 1), the minimum number of examinations was determined by comparing the intraclass correlation coefficient (ICC) of subsets of the first 2 to 14 measurements with that from 15 measurements. In 454 patients (group 2), 2 SWE sessions were performed in the right lobe within 1 day. Technical failure was defined as when no or little signal was obtained in the elastogram during the first 5 acquisitions; unreliable SWE results were defined as when the interquartile range/median liver stiffness value exceeded 30%. Intraobserver reproducibility was assessed using ICCs and Bland-Altman plots. RESULTS In group 1, the ICCs did not significantly increase after the first 6 measurements. In group 2, there were technical failures and unreliable results in 47 patients (10.35%) and 74 patients (16.29%), respectively. In 407 patients, after excluding technical failures, there was no significant difference in the median liver stiffness values between the 2 sessions (6.95 versus 6.86 kPa; P > .05). The overall intraobserver reproducibility was excellent (ICC, 0.95). CONCLUSIONS In this study, the optimal minimum number of SWE measurements was 6, and SWE using 6 measurements showed excellent intraobserver reproducibility.
Collapse
Affiliation(s)
- Jeong Hee Yoon
- Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
| | | | | | | |
Collapse
|
|
15
|
Cui XW, Friedrich-Rust M, Molo CD, Ignee A, Schreiber-Dietrich D, Dietrich CF. Liver elastography, comments on EFSUMB elastography guidelines 2013. World J Gastroenterol 2013; 19:6329-6347. [PMID: 24151351 PMCID: PMC3801303 DOI: 10.3748/wjg.v19.i38.6329] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Revised: 08/11/2013] [Accepted: 09/16/2013] [Indexed: 02/06/2023] Open
Abstract
Recently the European Federation of Societies for Ultrasound in Medicine and Biology Guidelines and Recommendations have been published assessing the clinical use of ultrasound elastography. The document is intended to form a reference and to guide clinical users in a practical way. They give practical advice for the use and interpretation. Liver disease forms the largest section, reflecting published experience to date including evidence from meta-analyses with shear wave and strain elastography. In this review comments and illustrations on the guidelines are given.
Collapse
|
|
16
|
Roca B, Resino E, Torres V, Herrero E, Penades M. Interobserver discrepancy in liver fibrosis using transient elastography. J Viral Hepat 2012; 19:711-5. [PMID: 22967102 DOI: 10.1111/j.1365-2893.2012.01608.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Transient elastography is a useful method to assess liver fibrosis, but uncertainties still exist regarding reliability and reproducibility of the technique. We aimed to improve knowledge on interobserver variability with the procedure and tried to find factors associated with such variability. This was a cross-sectional study to compare the results of transient elastography performed by two different operators, one test made just after the other. We assessed both results with correlation tests and with repeated parametric or nonparametric tests, as needed. We also carried out a multivariate analysis to find factors associated with discrepancy in the results obtained by the two operators. We included a total of 333 pairs of transient elastography tests, belonging to 274 different patients. A total of 325 pairs of tests (97.6%) were valid. Results of the first and the second tests were, respectively, median (and interquartile range) of direct measurement 6.2 (4.6-10.6) and 6.0 (4.4-10.1) kPa (P = 0.012), and mean ± standard deviation of log(10) of direct measurement 0.892 ± 0.316 and 0.871 ± 0.324 (P = 0.001). In 87 pairs of tests (26.7%), a discrepancy of at least 2 kPa between both results was found, and in 15 pairs of tests (4.6%), a discrepancy of at least 10 kPa was found. Discordance of at least one stage between both measurements was noted in 74 pairs of tests (22.8%). An association was found between higher stiffness and discrepancy between both operators (P < 0.001). Although transient elastography is a very convenient test to assess liver fibrosis in clinical practice, interobserver discrepancy in results is common and represents a significant problem with the technique. Discrepant results are more common in patients with higher values of stiffness.
Collapse
Affiliation(s)
- B Roca
- Medicine Department, Hospital General of Castellon, University Jaume I and University of Valencia, Castellon, Spain
| | | | | | | | | |
Collapse
|