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Sahshong P, Chandra A, Mercado-Shekhar KP, Bhatt M. Deep denoising approach to improve shear wave phase velocity map reconstruction in ultrasound elastography. Med Phys 2025; 52:1481-1499. [PMID: 39714072 DOI: 10.1002/mp.17581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 11/25/2024] [Accepted: 11/25/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Measurement noise often leads to inaccurate shear wave phase velocity estimation in ultrasound shear wave elastography. Filtering techniques are commonly used for denoising the shear wavefields. However, these filters are often not sufficient, especially in fatty tissues where the signal-to-noise ratio (SNR) can be very low. PURPOSE The purpose of this study is to develop a deep learning approach for denoising shear wavefields in ultrasound shear wave elastography. This may lead to improved reconstruction of shear wave phase velocity image maps. METHODS The study addresses noise by transforming particle velocity data into a time-frequency representation. A neural network with encoder and decoder convolutional blocks effectively decomposes the input and extracts the signal of interest, improving the SNR in high-noise scenarios. The network is trained on simulated phantoms with elasticity values ranging from 3 to 60 kPa. A total of 1 85 570 samples with 80%-20 % $\%$ split were used for training and validation. The approach is tested on experimental phantom and ex-vivo goat liver tissue data. Performance was compared with the traditional filtering methods such as bandpass, median, and wavelet filtering. Kruskal-Wallis one-way analysis of variance was performed to check statistical significance. Multiple comparisons were performed using the Mann-Whitney U test and Holm-Bonferroni adjustment ofp - values $p-{\rm values}$ . RESULTS The results are evaluated using SNR and the percentage of pixels that can be reconstructed in the phase velocity maps. The SNR levels in experimental data improved from -2 to 9.9 dB levels to 15.6 to 30.3 dB levels. Kruskal-Wallis one-way analysis showed statistical significance (p < 0.05 $p<0.05$ ). Multiple comparisons with p-value corrections also showed statistically significant improvement when compared to the bandpass and wavelet filtering scheme (p < 0.05 $p<0.05$ ). Smoother phase velocity maps were reconstructed after denoising. The coefficient of variation is less than5 % $5\%$ in CIRS phantom and less than18 % $18\%$ in ex-vivo goat liver tissue. CONCLUSIONS The proposed approach demonstrates improvement in shear wave phase velocity image map reconstruction and holds promise that deep learning methods can be effectively utilized to extract true shear wave signal from measured noisy data.
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Affiliation(s)
- Phidakordor Sahshong
- Department of Electronics and Electrical Engineering, Indian Institute of Technology Guwahati, Assam, India
| | - Akash Chandra
- Department Of Biological Sciences And Engineering, Indian Institute of Technology, Gandhinagar, Gujarat, India
| | - Karla P Mercado-Shekhar
- Department Of Biological Sciences And Engineering, Indian Institute of Technology, Gandhinagar, Gujarat, India
| | - Manish Bhatt
- Department of Electronics and Electrical Engineering, Indian Institute of Technology Guwahati, Assam, India
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Duarte-Rojo A, Taouli B, Leung DH, Levine D, Nayfeh T, Hasan B, Alsawaf Y, Saadi S, Majzoub AM, Manolopoulos A, Haffar S, Dundar A, Murad MH, Rockey DC, Alsawas M, Sterling RK. Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline. Hepatology 2025; 81:725-748. [PMID: 38489521 DOI: 10.1097/hep.0000000000000852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/19/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND AIMS Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.
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Affiliation(s)
- Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, Northwestern Medicine and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Daniel H Leung
- Department of Pediatrics, Baylor College of Medicine and Division of Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Houston, Texas, USA
| | - Deborah Levine
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Tarek Nayfeh
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Hasan
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Samer Saadi
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Samir Haffar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Ayca Dundar
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Mouaz Alsawas
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Richard K Sterling
- Section of Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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Cho Y. Evaluation of Liver Fibrosis through Noninvasive Tests in Steatotic Liver Disease. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:215-222. [PMID: 39582309 DOI: 10.4166/kjg.2024.103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 11/26/2024]
Abstract
Liver fibrosis, a critical predictor of the prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD), is traditionally diagnosed via biopsy. Nevertheless, non-invasive alternatives, such as serum biomarkers, vibration-controlled transient elastography, and magnetic resonance elastography, have become prominent because of the limitations of biopsies. Serum biomarkers, such as fibrosis-4 index and NFS Score, are also used widely, offering reliable diagnostic performance for advanced fibrosis. Vibration-controlled transient elastography and shear wave elastography provide further non-invasive evaluations with high diagnostic accuracy, particularly for advanced fibrosis, but the results may be affected by factors such as obesity. Magnetic resonance elastography, with superior diagnostic accuracy and operator independence, is a promising method, but its high cost and limited availability restrict its widespread use. Emerging algorithms, such as NIS4, FAST, or MAST score, have strong potential in identifying high-risk metabolic dysfunction-associated steatohepatitis patients. The integration of multiple non-invasive methods can optimize diagnostic accuracy, reducing the need for invasive biopsies while identifying patients at risk of liver-related complications. Further research is needed to refine these diagnostic tools and improve accessibility.
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Affiliation(s)
- Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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Sarkar Das T, Meng X, Abdallah M, Bilal M, Sarwar R, Shaukat A. An Assessment of the Feasibility, Patient Acceptance, and Performance of Point-of-Care Transient Elastography for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2024; 14:2478. [PMID: 39594144 PMCID: PMC11592655 DOI: 10.3390/diagnostics14222478] [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: 07/28/2024] [Revised: 10/12/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024] Open
Abstract
Background: Vibration-Controlled Transient Elastography (VCTE) with FibroScan is a non-invasive, reliable diagnostic tool for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD), enabling early detection and management to prevent severe liver diseases. VCTE's ease and portability suit primary care, streamlining referrals, promoting lifestyle changes, reducing costs, and benefiting underserved communities. Methods: Studies on point-of-care VCTE were systematically reviewed, followed by meta-analysis using a random-effects model. Pooled proportions with 95% confidence intervals were reported, and heterogeneity was assessed using I2%. Results: A total of twenty studies from 14 countries, including 6159 patients, were analyzed, with three studies from France, two from the U.S., and four from China. The population had a slight male preponderance, with a mean age range of 35-73 years and a BMI range of 24.4-41.1%. The diagnostic accuracy for detecting any fibrosis (≥F1) was reported in four studies (n = 210) with an AUC of 0.74, sensitivity of 69.5%, and specificity of 70.6%. For significant fibrosis (≥F2), eight studies (n = 650) reported an AUC of 0.69, sensitivity of 81.7%, and specificity of 64.6%. Advanced fibrosis (≥F3) was evaluated in 10 studies (n = 619), with an AUC of 0.84, sensitivity of 88.1%, and specificity of 63.8%. Cirrhosis (F4) was assessed in nine studies (n = 533), with an AUC of 0.65, sensitivity of 87.5%, and specificity of 62.6%. Steatosis diagnoses across stages S1 to S3 showed increasing diagnostic accuracies, with AUCs of 0.85, 0.76, and 0.80, respectively. Probe type and BMI were significant covariates influencing diagnostic performance for both fibrosis and steatosis, while the percentage of male participants also showed significant associations. Conclusions: VCTE shows high diagnostic accuracy for fibrosis and steatosis in MASLD patients at the point of care. Future research should assess its implementation in fibroscan settings.
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Affiliation(s)
- Taranika Sarkar Das
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
| | - Xucong Meng
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
| | - Mohamed Abdallah
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Mohammad Bilal
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Raiya Sarwar
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
| | - Aasma Shaukat
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU, on behalf of The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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Chon YE, Jin YJ, An J, Kim HY, Choi M, Jun DW, Kim MN, Han JW, Lee HA, Yu JH, Kim SU. Optimal cut-offs of vibration-controlled transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. Clin Mol Hepatol 2024; 30:S117-S133. [PMID: 39165159 PMCID: PMC11493355 DOI: 10.3350/cmh.2024.0392] [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: 05/24/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND/AIMS Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF. METHODS Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. RESULTS A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80-0.86), 0.83 (0.80-0.86), 0.87 (0.84-0.90), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86-0.92), 0.92 (0.89-0.94), 0.89 (0.86-0.92), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. CONCLUSION VCTE (7.1-7.9 kPa) and MRE (3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.
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Affiliation(s)
- Young Eun Chon
- Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, College of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Miyoung Choi
- Division of Health Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency (NECA), Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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López Tórrez SM, Ayala CO, Ruggiro PB, Costa CAD, Wagner MB, Padoin AV, Mattiello R. Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of over 40,000 participants. Front Nutr 2024; 11:1284509. [PMID: 38419854 PMCID: PMC10899345 DOI: 10.3389/fnut.2024.1284509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
Introduction A prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established. Objective The meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD. Methods Adults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study's risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Results In total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87. Conclusion The results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525].
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Affiliation(s)
- Sergio M. López Tórrez
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Camila O. Ayala
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Paula Bayer Ruggiro
- School of Medicine, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Caroline Abud Drumond Costa
- School of Medicine, Postgraduate Program in Pediatrics and Child Health, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Mario B. Wagner
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Alexandre Vontobel Padoin
- School of Medicine, Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica de Rio Grande do Sul (PUCRS), Porto Alegre, Brazil
| | - Rita Mattiello
- School Medicine, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
- School of Medicine, Postgraduate Program in Epidemiology, Universidade Federal de Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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8
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Boeriu A, Dobru D, Fofiu C. Non-Invasive Diagnostic of NAFLD in Type 2 Diabetes Mellitus and Risk Stratification: Strengths and Limitations. Life (Basel) 2023; 13:2262. [PMID: 38137863 PMCID: PMC10744403 DOI: 10.3390/life13122262] [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: 10/07/2023] [Revised: 10/26/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
The progressive potential of liver damage in type 2 diabetes mellitus (T2DM) towards advanced fibrosis, end-stage liver disease, and hepatocarcinoma has led to increased concern for quantifying liver injury and individual risk assessment. The combination of blood-based markers and imaging techniques is recommended for the initial evaluation in NAFLD and for regular monitoring to evaluate disease progression. Continued development of ultrasonographic and magnetic resonance imaging methods for accurate quantification of liver steatosis and fibrosis, as well as promising tools for the detection of high-risk NASH, have been noted. In this review, we aim to summarize available evidence regarding the usefulness of non-invasive methods for the assessment of NAFLD in T2DM. We focus on the power and limitations of various methods for diagnosis, risk stratification, and patient monitoring that support their implementation in clinical setting or in research field.
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Affiliation(s)
- Alina Boeriu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania;
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Daniela Dobru
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania;
- Gastroenterology Department, Mures County Clinical Hospital, 540103 Targu Mures, Romania
| | - Crina Fofiu
- Gastroenterology Department, University of Medicine Pharmacy, Sciences, and Technology “George Emil Palade” Targu Mures, 540142 Targu Mures, Romania;
- Internal Medicine Department, Bistrita County Clinical Hospital, 420094 Bistrita, Romania
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Xu X, Jin J, Liu Y. Performance of FibroScan in grading steatosis and fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Arab J Gastroenterol 2023; 24:189-197. [PMID: 37996351 DOI: 10.1016/j.ajg.2023.08.003] [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: 03/05/2021] [Revised: 12/02/2021] [Accepted: 08/18/2023] [Indexed: 11/25/2023]
Abstract
OBJECTIVE Biopsy remains the gold standard for the diagnosis of Non-alcoholic fatty liver disease (NAFLD). To investigate the diagnostic value of FibroScan based on biopsy and range of cut-offs for steatosis and fibrosis, we explored the grade of steatosis and fibrosis. METHOD A simultaneous search was performed on cohort studies published earlier than October 8, 2020,in the PubMed, Web of Science, Sinomed, CNKI, VIP, and WanFang databases. Next,we screened qualified studies. The data were mainly analysed in RevMan and complemented in STATA. RESULTS The area under the receiver operating characteristic of FibroScan in identifying the stage of steatosis for ≥ S1 was 0.90 (sensitivity:89%; specificity:92%), that for ≥ S2 was 0.82 (sensitivity:89%;specificity:70%) and that for S3 was 0.79 (sensitivity:83%; specificity:63%).The area under the receiver operating characteristic of FibroScan in identifying the stage of fibrosis for ≥ F1 was 0.86 (sensitivity:81%;specificity:77%),that for ≥ F2 was 0.80 (sensitivity: 75%; specificity:82%), that for ≥ F3 was 0.94 (sensitivity:87%; specificity: 89%) and that for F4 was 0.97 (sensitivity: 94%; specificity:91%). CONCLUSION FibroScan, a promising and cost-effective technique, can provide an accurate noninvasive approach for quantifying and staging hepatic steatosis and fibrosis in NAFLD, particularly for advanced fibrosis and cirrhosis. Further studies are needed to explore the relationship between steatosis and fibrosis based on the same group. Additionally, NASH is the key stage of NAFLD. Early diagnosis and intervention can help reduce the incidence of liver cirrhosis. However, no large study has investigated the significance of FibroScan in the diagnosis of NASH confirmed by pathology.
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Affiliation(s)
- Xiaotong Xu
- Jilin University Hosp 1, Dept Hepatol, Changchun, People's Republic of China
| | - Jinglan Jin
- Jilin University Hosp 1, Dept Hepatol, Changchun, People's Republic of China.
| | - Yuwei Liu
- Jilin University Hosp 1, Dept Hepatol, Changchun, People's Republic of China
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Ding Y, Wang Z, Niu H, Deng Q, Wang Y, Xia S. FIB-4 is closer to FibroScan screen results to detecting advanced liver fibrosis and maybe facilitates NAFLD warning. Medicine (Baltimore) 2023; 102:e34957. [PMID: 37653822 PMCID: PMC10470683 DOI: 10.1097/md.0000000000034957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 07/13/2023] [Accepted: 08/04/2023] [Indexed: 09/02/2023] Open
Abstract
To assess the relationship between clinical biochemical characteristics and steatosis or fibrosis by Fibroscan in non-alcoholic fatty liver disease (NAFLD) patients in order to seek the simple effective screening method closed to the results of the fibroScan measurement. A cross-sectional study was conducted on 188 patients with NAFLD who underwent FibroScan examinations. Demographic data and clinical biochemical characteristics were collected and analyzed. The result showed elevated serum uric acid (SUA) (P = .023, odds ratio [OR = 1.005, 95% CI (1.001-1.009) and metabolic syndrome (MetS) (P = .000, OR = 4.549, 95%CI (1.974-10.484) were associated with severe steatosis (controlled attenuation parameter, CAP ≥ 300 dB/m). The magnitude of liver stiffness measured using FibroScan was positively correlated with aspartate transaminase/alanine aminotransferase (AST/ALT) ratio (R = 0.419, P = .000), AST to platelet ratio index (APRI) score (R = 0.309, P = .000), and Fibrosis-4 score (FIB-4) (R = 0.507, P = .000). The areas under the receiver operating curve (ROC) of AST/ALT, APRI, and FIB-4 for mild or severe fibrosis were 0.563, 0.696, and 0.728, respectively, and those for advanced fibrosis were 0.648, 0.750, and 0.821, respectively. The FIB-4 index cutoff value was 1.65 with a sensitivity of 68.3% and specificity of 89.8% during the diagnosis of advanced fibrosis. MetS and elevated SUA are associated with severe steatosis according to the CAP value screen, whereas FIB-4, as the fibrosis score method, is closer to the liver stiffness measurement results from FibroScan, which may facilitate early warning of NAFLD in the community or in remote areas.
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Affiliation(s)
- Yuping Ding
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin, China
| | - Zuoyu Wang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin, China
| | - Haiyan Niu
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin, China
| | - Quanjun Deng
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin, China
| | - Yanan Wang
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
| | - Shihai Xia
- Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China
- Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin, China
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11
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Villani R, Lupo P, Sangineto M, Romano AD, Serviddio G. Liver Ultrasound Elastography in Non-Alcoholic Fatty Liver Disease: A State-of-the-Art Summary. Diagnostics (Basel) 2023; 13:1236. [PMID: 37046454 PMCID: PMC10093430 DOI: 10.3390/diagnostics13071236] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/21/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease which is currently the most common hepatic disorder affecting up to 38% of the general population with differences according to age, country, ethnicity and sex. Both genetic and acquired risk factors such as a high-calorie diet or high intake of saturated fats have been associated with obesity, diabetes and, finally, NAFLD. A liver biopsy has always been considered essential for the diagnosis of NAFLD; however, due to several limitations such as the potential occurrence of major complications, sampling variability and the poor repeatability in clinical practice, it is considered an imperfect option for the evaluation of liver fibrosis over time. For these reasons, a non-invasive assessment by serum biomarkers and the quantification of liver stiffness is becoming the new frontier in the management of patients with NAFLD and liver fibrosis. We present a state-of-the-art summary addressing the methods for the non-invasive evaluation of liver fibrosis in NAFLD patients, particularly the ultrasound-based techniques (transient elastography, ARFI techniques and strain elastography) and their optimal cut-off values for the staging of liver fibrosis.
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Affiliation(s)
- Rosanna Villani
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Pierluigi Lupo
- Department of Radiology, University of Foggia, 71122 Foggia, Italy
| | - Moris Sangineto
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Antonino Davide Romano
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
| | - Gaetano Serviddio
- Liver Unit, C.U.R.E. (University Centre for Liver Disease Research and Treatment), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
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12
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Duseja A, Singh S, De A, Madan K, Rao PN, Shukla A, Choudhuri G, Saigal S, Shalimar, Arora A, Anand AC, Das A, Kumar A, Eapen CE, Devadas K, Shenoy KT, Panigrahi M, Wadhawan M, Rathi M, Kumar M, Choudhary NS, Saraf N, Nath P, Kar S, Alam S, Shah S, Nijhawan S, Acharya SK, Aggarwal V, Saraswat VA, Chawla YK. Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD). J Clin Exp Hepatol 2023; 13:273-302. [PMID: 36950481 PMCID: PMC10025685 DOI: 10.1016/j.jceh.2022.11.014] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 11/16/2022] [Accepted: 11/29/2022] [Indexed: 03/24/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.
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Key Words
- AASLD, American Association for the Study of Liver Diseases
- ALD, alcohol-associated liver disease
- ALT, alanine aminotransferase
- APRI, AST-platelet ratio index
- AST, aspartate aminotransferase
- BMI, body mass index
- CAP, controlled attenuation parameter
- CHB, chronic Hepatitis B
- CHC, chronic Hepatitis C
- CK-18, Cytokeratin-18
- CKD, chronic kidney disease
- CRN, Clinical Research Network
- CVD, cardiovascular disease
- DAFLD/DASH, dual etiology fatty liver disease or steatohepatitis
- EBMT, endoscopic bariatric metabolic therapy
- ELF, enhanced liver fibrosis
- FAST, FibroScan-AST
- FIB-4, fibrosis-4
- FLIP, fatty liver inhibition of progression
- FXR, farnesoid X receptor
- GLP-1, glucagon-like peptide-1
- HCC, hepatocellular carcinoma
- INASL, Indian National Association for Study of the Liver
- LAI, liver attenuation index
- LSM, liver stiffness measurement
- MAFLD
- MAFLD, metabolic dysfunction-associated fatty liver disease
- MR-PDFF, magnetic resonance – proton density fat fraction
- MRE, magnetic resonance elastography
- MetS, metabolic syndrome
- NAFL:, nonalcoholic fatty liver
- NAFLD, nonalcoholic fatty liver disease
- NAS, NAFLD activity score
- NASH
- NASH, nonalcoholic steatohepatitis
- NCD, noncommunicable diseases
- NCPF, noncirrhotic portal fibrosis
- NFS, NAFLD fibrosis score
- NHL, non-Hodgkin's lymphoma
- NPCDCS, National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke
- OCA, obeticholic acid
- PPAR, peroxisome proliferator activated receptor
- PTMS, post-transplant metabolic syndrome
- SAF, steatosis, activity, and fibrosis
- SGLT-2, sodium-glucose cotransporter-2
- SWE, shear wave elastography
- T2DM, DM: type 2 diabetes mellitus
- USG, ultrasound
- VAT, visceral adipose tissue
- VCTE, vibration controlled transient elastography
- fatty liver
- hepatic steatosis
- nonalcoholic steatohepatitis
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Affiliation(s)
- Ajay Duseja
- Departmentof Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - S.P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, India
| | - Arka De
- Departmentof Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Kaushal Madan
- Max Centre for Gastroenterology, Hepatology and Endoscopy, Max Hospitals, Saket, New Delhi, India
| | - Padaki Nagaraja Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, India
| | - Gourdas Choudhuri
- Department of Gastroenterology and Hepato-Biliary Sciences, Fortis Memorial Research Institute, Gurugram, India
| | - Sanjiv Saigal
- Max Centre for Gastroenterology, Hepatology and Endoscopy, Max Hospitals, Saket, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Anil Arora
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Anil C. Anand
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Ashim Das
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | | | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Trivandrum, India
| | | | - Manas Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases, BLK Super Speciality Hospital, Delhi, India
| | - Manish Rathi
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Neeraj Saraf
- Department of Hepatology, Medanta, The Medicity, Gurugram, India
| | - Preetam Nath
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Sanjib Kar
- Department of Gastroenterology and Hepatology, Gastro Liver Care, Cuttack, India
| | - Seema Alam
- Department of PediatricHepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Samir Shah
- Department of Hepatology, Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Sandeep Nijhawan
- Department of Gastroenterology, Sawai Man Singh Medical College, Jaipur, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Vinayak Aggarwal
- Department of Cardiology, Fortis Memorial Research Institute, Gurugram, India
| | - Vivek A. Saraswat
- Department of Hepatology, Pancreatobiliary Sciences and Liver Transplantation, Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, India
| | - Yogesh K. Chawla
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
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Elhence A, Anand A, Biswas S, Vaishnav M, Yadav R, Das P, Panwar R, Agarwal S, Gamanagatti S, Kumar R, Shalimar. Compensated Advanced Chronic Liver Disease in Nonalcoholic Fatty Liver Disease: Two-Step Strategy is Better than Baveno Criteria. Dig Dis Sci 2023; 68:1016-1025. [PMID: 35670897 DOI: 10.1007/s10620-022-07579-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 05/23/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. METHODS In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. RESULTS Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9-82.8%) and a specificity of 93.4% (89.7-96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3-96.8%) and 88.5% (83.9-92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161-11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098-2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609-0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506-.736) and Zhou (AUROC 0.523, CI 0.403-0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. CONCLUSION A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients.
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Affiliation(s)
- Anshuman Elhence
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Abhinav Anand
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sagnik Biswas
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Panwar
- Department of Gastrointestinal Surgery and Liver Transplant, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Agarwal
- Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
| | - Shivanand Gamanagatti
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
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14
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Liu J, Yu X, Ting HJ, Wang X, Xu S, Wang Y, Zhang S, Wang JW, Liu B. Myeloperoxidase-Sensitive T1 and T2 Switchable MR Imaging for Diagnosis of Nonalcoholic Steatohepatitis. ACS NANO 2023; 17:3324-3333. [PMID: 36773320 DOI: 10.1021/acsnano.2c06233] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is the critical stage in the development of nonalcoholic fatty liver disease (NAFLD) from simple and reversible steatosis to irreversible cirrhosis and even hepatocellular carcinoma (HCC). Thus, the diagnosis of NASH is important for preventing the progress of NAFLD into a fatal condition. The oxidative enzyme myeloperoxidase (MPO), which is mostly produced by polymorphonuclear neutrophil granulocytes (NEU), has been identified as a key player in lipid peroxidation in inflamed tissues. Considering that the expression of MPO was much higher in NASH than in the nonalcoholic fatty liver (NAFL) with steatosis, we designed a nanoparticle platform based on ultrasmall iron oxide (USIO) nanoparticles to realize MPO-sensitive NASH diagnosis. After modification of USIO nanoparticles with amphiphilic poly(ethylene glycol) (PEG) and conjugation with 5-hydroxytryptamine (5HT), a physiological substrate for MPO, the final nanocomposite (USIO-DA-PEG-5HT) revealed MPO-mediated aggregation at the inflammatory site of NASH. Meanwhile, the intrinsic T1-weighted magnetic resonance (MR) signal of dispersed USIO-DA-PEG-5HT nanoparticles diminishes, while the T2-weighted MR signal is amplified owing to the aggregation effect. These USIO-DA-PEG-5HT nanoprobes offer great potential for improving NASH MR imaging diagnostic accuracy and sensitivity compared to existing molecular MR contrast agents with a single imaging modality.
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Affiliation(s)
- Jingjing Liu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China
| | - Xiaodong Yu
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
| | - Hui Jun Ting
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
| | - Xiaoyuan Wang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
| | - Shidang Xu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
| | - Yuanbo Wang
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
| | - Sitong Zhang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
| | - Jiong-Wei Wang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
- Cardiovascular Research Institute, National University Heart Centre Singapore, Singapore 117599, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore
| | - Bin Liu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
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15
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Jindal A, Agarwal S, Sharma S, Kumar M, Saraya A, Sarin SK. Assessment of the Performance of Non-invasive Criteria for the Evaluation of Clinically Significant Portal Hypertension in Patients with Compensated Advanced Chronic Liver Disease. Dig Dis Sci 2022; 68:2149-2157. [PMID: 36562888 DOI: 10.1007/s10620-022-07778-0] [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: 02/05/2022] [Accepted: 11/22/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Assessment of clinically significant portal hypertension (CSPH) non-invasively using a combination of liver stiffness measurement (LSM) and platelet counts is proposed as an alternative to hepatic venous pressure gradient (HVPG) estimation. Utility of these criteria in compensated advanced chronic liver disease (cACLD) patients of different etiologies including nonalcoholic steatohepatitis (NASH) with BMI > 30 kg/m2 was studied in a large cohort. METHODS Consecutive patients of cACLD with available anthropometric and laboratory details, LSM, and HVPG were included in a retrospective analysis. A LSM of ≥ 25 kPa alone and LSM ≤ 15 kPa plus platelets ≥ 150 × 109/L were evaluated as non-invasive rule-in and rule-out criteria for CSPH, respectively. The NASH-ANTICPATE model (composite of BMI, platelets, and LSM) was evaluated in patients with obese NASH. RESULTS Patients with cACLD (n = 626) (mean age: 50.8 ± 12.4 years, 74.2% males) with alcohol (ALD, 30.3%), NASH (26.4%), hepatitis C (HCV, 16.6%), hepatitis B (HBV,10.2%) etiology were included. The prevalence of CSPH was > 80% across all etiologies except in HBV (62.5%) and in obese non-NASH (71-72%). The rule-in criteria had a PPV > 90% for all etiologies except in HBV (80.8%). The rule-out criteria had a negative predictive value (NPV) of 65%, 53%, and 40% in ALD, HCV, and NASH, respectively. The NASH-ANTCIPATE model had specificity of 100% and NPV of 33% to detect CSPH in obese NASH (n = 62). CONCLUSIONS LSM ≥ 25 kPa predicted CSPH in most etiologies except HBV. A significant proportion of patients have CSPH despite satisfying the rule-out criteria. The NASH-ANTICIPATE model is specific but fails to exclude CSPH in nearly two-third patients with obesity and NASH. There is a need for precise disease-specific non-invasive models for detecting CSPH.
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Affiliation(s)
- Ankur Jindal
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India, 110070
| | - Samagra Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India, 110029
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India, 110029
| | - Manoj Kumar
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India, 110070
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India, 110029
| | - Shiv Kumar Sarin
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India, 110070.
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16
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Wang J, Qin T, Sun J, Li S, Cao L, Lu X. Non-invasive methods to evaluate liver fibrosis in patients with non-alcoholic fatty liver disease. Front Physiol 2022; 13:1046497. [PMID: 36589424 PMCID: PMC9794751 DOI: 10.3389/fphys.2022.1046497] [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: 09/16/2022] [Accepted: 11/15/2022] [Indexed: 12/15/2022] Open
Abstract
Non-alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease that is strongly related to insulin resistance and metabolic syndrome, and it has become the most common liver disorder in developed countries. NAFLD embraces the full pathological process of three conditions: steatosis, non-alcoholic steatohepatitis, and finally, cirrhosis. As NAFLD progresses, symptoms will become increasingly severe as fibrosis develops. Therefore, evaluating the fibrosis stage is crucial for patients with NAFLD. A liver biopsy is currently considered the gold standard for staging fibrosis. However, due to the limitations of liver biopsy, non-invasive alternatives were extensively studied and validated in patients with NAFLD. The advantages of non-invasive methods include their high safety and convenience compared with other invasive approaches. This review introduces the non-invasive methods, summarizes their benefits and limitations, and assesses their diagnostic performance for NAFLD-induced fibrosis.
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Affiliation(s)
- Jincheng Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tao Qin
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jinyu Sun
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shiwu Li
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, China
| | - Lihua Cao
- Liver Disease Center, Qinhuangdao Third Hospital, Qinhuangdao, China,*Correspondence: Xiaojie Lu, ; Lihua Cao,
| | - Xiaojie Lu
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China,*Correspondence: Xiaojie Lu, ; Lihua Cao,
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Cao YT, Xiang LL, Qi F, Zhang YJ, Chen Y, Zhou XQ. Accuracy of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) for assessing steatosis and fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. EClinicalMedicine 2022; 51:101547. [PMID: 35844772 PMCID: PMC9284399 DOI: 10.1016/j.eclinm.2022.101547] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 06/16/2022] [Accepted: 06/20/2022] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and among the non-invasive tests, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) have shown better diagnostic performance in NAFLD. This meta-analysis aimed to evaluate the performance of CAP and LSM for assessing steatosis and fibrosis in NAFLD. METHODS We searched the PubMed, Web of Science, Cochrane Library, and Embase databases for relevant articles published up to February 13th, 2022, and selected studies that met the inclusion and exclusion criteria, and evaluated the quality of evidence. Then we pooled sensitivity (SE), specificity (SP), and area under receiver operating characteristic (AUROC) curves. A random effect model was applied regardless of heterogeneity. Meta-regression analysis and subgroup analysis were performed to explore heterogeneity, and Fagan plot analysis was used to evaluate clinical utility. This meta-analysis was completed in Nanjing, Jiangsu and registered on PROSPERO (CRD42022309965). FINDINGS A total of 10537 patients from 61 studies were included in our meta-analysis. The AUROC of CAP were 0·924, 0·794 and 0·778 for steatosis grades ≥ S1, ≥ S2 and = S3, respectively, and the AUROC of LSM for detecting fibrosis stages ≥ F1, ≥ F2, ≥ F3, and = F4 were 0·851, 0·830, 0·897 and 0·925, respectively. Subgroup analysis revealed that BMI ≥ 30 kg/m² had lower accuracy for diagnosing S ≥ S1, ≥ S2 than BMI<30 kg/m². For the mean cut-off values, significant differences were found in CAP values among different body mass index (BMI) populations and LSM values among different regions. For diagnosing S ≥ S1, ≥ S2 and = S3, the mean CAP cut-off values for BMI ≥ 30 kg/m² were 30·7, 28·2, and 27·9 dB/m higher than for BMI < 30 kg/m² (P = 0·001, 0·001 and 0·018, respectively). For diagnosing F ≥ F2 and = F4, the mean cut-off values of Europe and America were 0·96 and 2·03 kPa higher than Asia (P = 0·027, P = 0·034), respectively. In addition, the results did not change significantly after sensitivity analysis and the trim and fill method to correct for publication bias, proving that the conclusions are robust. INTERPRETATION The good performance of CAP and LSM for the diagnosis of mild steatosis (S ≥ S1), advanced liver fibrosis (F ≥ F3), and cirrhosis (F = F4) can be used to screen for NAFLD in high-risk populations. Of note, the accuracy of CAP for the detection of steatosis in patients with obesity is reduced and requires specific diagnostic values. For LSM, the same diagnostic values can be used when the appropriate probes are selected based on BMI and the automated probe selection tool. The performance of CAP and LSM in assessing steatosis in patients with obesity, moderate to severe steatosis, and low-grade fibrosis should be further validated and improved in the future. FUNDING The study was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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Affiliation(s)
- Yu-tian Cao
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Liu-lan Xiang
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Fang Qi
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yu-juan Zhang
- The first clinical medical college of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Yi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xi-qiao Zhou
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
- Corresponding author at: Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
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Agarwal S, Sharma S, Jindal A, Singh S, Jagdish R, Gunjan D, Sarin SK, Saraya A. Application of Noninvasive Tools to Decide the Need for Beta-Blockers for Variceal Bleeding Prophylaxis in Compensated Advanced Liver Disease: A Decision Curve Analysis. J Clin Exp Hepatol 2022; 12:917-926. [PMID: 35677505 PMCID: PMC9168689 DOI: 10.1016/j.jceh.2021.09.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 09/19/2021] [Indexed: 12/12/2022] Open
Abstract
Background and aims Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up. Methods This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy. Results A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9-35) months. The 1-year and 3-year rate of VB with all NITs was 5.7-7.4% and 13.2-16.4% among high-risk and 0-2.3% and 0-5% among low-risk subgroups, respectively (P < 0.001) in both viral and nonviral aetiologies. Among patients classified as low risk on Baveno-VI criteria, none developed VB on follow-up. At thresholds of <3% event rate of VB, Baveno-VI (NNT-176), platelet-albumin (NNT-576) and anticipate platelet (NNT-233) criteria were superior, whereas endoscopic stratification was superior above this event rate on DCA. Conclusions The use of both elastography and blood-based NITs at baseline can accurately identify the need for NSBB for VB prophylaxis in patients of cACLD on follow-up.
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Key Words
- Baveno-VI
- DCA, Decision curve analysis
- EBL, Endoscopic band ligation
- HCC, Hepatocellular carcinoma
- HE, Hepatic encephalopathy
- HRVs, High risk varices
- LRVs, Low risk varices
- LSM, Liver stiffness measurement
- NITs, Non-invasive tools
- NNT, Number needed to treat
- NSBB, Non-selective beta blockers
- PVT, Portal venous thrombosis
- VB, Variceal bleeding
- VNT, Varices needing treatment
- cACLD, Compensated advanced chronic liver disease
- decision thresholds
- noninvasive tools
- variceal bleeding
- varices needing treatment
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Affiliation(s)
- Samagra Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110026, India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110026, India
| | - Ankur Jindal
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Sushrut Singh
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakesh Jagdish
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110026, India
| | - Shiv K. Sarin
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110026, India
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Diagnostic Feasibility of Magnetic Resonance Elastography Radiomics Analysis for the Assessment of Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. J Comput Assist Tomogr 2022; 46:505-513. [PMID: 35483092 DOI: 10.1097/rct.0000000000001308] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVE The aim of the study was to investigate the diagnostic feasibility of radiomics analysis using magnetic resonance elastography (MRE) to assess hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS One hundred patients with suspected NAFLD were retrospectively enrolled. All patients underwent a liver parenchymal biopsy. Magnetic resonance elastography was performed using a 3.0-T scanner. After multislice segmentation of MRE images, 834 radiomic features were analyzed using a commercial program. Radiologic features, such as median and mean values of the regions of interest and variable clinical features, were analyzed. A random forest regressor was used to extract important radiomic, radiological, and clinical features. A random forest classifier model was trained to use these features to classify the fibrosis stage. The area under the receiver operating characteristic curve was evaluated using a classifier for fibrosis stage diagnosis. RESULTS The pathological hepatic fibrosis stage was classified as low-grade fibrosis (stages F0-F1, n = 82) or clinically significant fibrosis (stages F2-F4, n = 18). Eight important features were extracted from radiomics analysis, with the 2 most important being wavelet-high high low gray level dependence matrix dependence nonuniformity-normalized and wavelet-high high low gray level dependence matrix dependence entropy. The median value of the multiple small regions of interest was identified as the most important radiologic feature. Platelet count has been identified as an important clinical feature. The area under the receiver operating characteristic curve of the classifier using radiomics was comparable with that of radiologic measures (0.97 ± 0.07 and 0.96 ± 0.06, respectively). CONCLUSIONS Magnetic resonance elastography radiomics analysis provides diagnostic performance comparable with conventional MRE analysis for the assessment of clinically significant hepatic fibrosis in patients with NAFLD.
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Duseja A, Singh SP, Mehta M, Shalimar, Venkataraman J, Mehta V, Devadas K, Kar SK, Goyal O, Nagral A, Saigal S, Nijhawan S, Praharaj D, Shukla A, Sharma B, Narayanasamy K, Kumar P, Rao PN, Arora A, Mehta R, Asati P, Ranjan P, Koshy A, Alam S, Mukewar S, Mukewar S, Mohan Prasad VG, Rastogi M, Sanyal AJ. Clinicopathological Profile and Outcome of a Large Cohort of Patients with Nonalcoholic Fatty Liver Disease from South Asia: Interim Results of the Indian Consortium on Nonalcoholic Fatty Liver Disease. Metab Syndr Relat Disord 2022; 20:166-173. [PMID: 35085026 DOI: 10.1089/met.2021.0104] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background: Previous data from South Asia and India had shown that patients with nonalcoholic fatty liver disease (NAFLD) have mild liver disease severity. There are no data regarding long-term clinical outcomes in patients with NAFLD from South Asia. The aim of the study was to evaluate the clinicopathological profile, severity of NAFLD, and clinical outcomes in a large cohort of patients with NAFLD from South Asia. Methods: In an ongoing real-life study [Indian Consortium on nonalcoholic fatty liver disease (ICON-D)], interim data captured across 23 centers in India over 18 months was analyzed for clinicopathological profile, severity of NAFLD, and hepatic/extrahepatic events on follow-up. Results: Of 4313 patients (mean age 45 ± 12.2 years, males 52%), data on metabolic risk factors in 3553 (82.3%) patients revealed that 378 (10.6%) were lean, 575 (16.2%) overweight, 2584 (72.7%) obese; metabolic syndrome in 1518 (42.7%) and at least one metabolic risk factor in 3292 (92.6%) patients. Evidence of significant or advanced fibrosis assessed with [aspartate transaminase to platelet ratio index (APRI), n = 3196 (74%)], [fibrosis-4 (FIB-4), n = 3554 (82.4%)], [NAFLD fibrosis score (NFS), n = 1924 (44.6%)], [Fibroscan, n = 2475, (57.3%)], and histology [n = 267 (6.2%)] was present in 682 (21.3%), 676 (19%), 397 (20.6%), 715 (29%), and 41 (15.4%) patients, respectively; 246 (10%) patients on Fibroscan and 22 (8.2%) on histology had evidence of cirrhosis. On a mean follow-up 43.5 months, hepatic and extrahepatic events recorded in 1353 (31.3%) patients showed that patients with compensated cirrhosis [71 (5.2%)] had more hepatic [26 (36.7%)] and extrahepatic events [8 (11.3%)] in comparison with those without cirrhosis (P < 0.0001). Conclusion: Around one fifth of patients with NAFLD in South Asia have significant liver disease. Both hepatic and extrahepatic events on follow-up are observed more commonly in patients with nonalcoholic steatohepatitis-related compensated cirrhosis.
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Affiliation(s)
- Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Shivaram P Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, India
| | - Manu Mehta
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Jayanthi Venkataraman
- Department of Hepatology, Sri Ramachandra Institute of Higher Education & Research, Chennai, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Trivandrum, India
| | | | - Omesh Goyal
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | | | | | | | - Dibyalochan Praharaj
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneshwar, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, India
| | - Brij Sharma
- Department of Gastroenterology, Indira Gandhi Medical College & Hospital, Shimla, India
| | | | - Pramod Kumar
- Centre of Liver Sciences, AIG Hospitals, Hyderabad, India
| | | | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Gangaram Hospital, New Delhi, India
| | - Rajiv Mehta
- Department of Gastroenterology, Surat Institute of Digestive Sciences, Surat, India
| | - Pankaj Asati
- NSC Bose Medical College and Hospital, Jabalpur, India
| | - Piyush Ranjan
- Department of Gastroenterology and Hepatology, Sir Gangaram Hospital, New Delhi, India
| | - Abraham Koshy
- Department of Hepatology, VPS Lakeshore, Kochi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | | | | | - Mukul Rastogi
- Department of Hepatology, Gastroenterology and Liver Transplant, Fortis Hospital, Noida, India
| | - Arun J Sanyal
- Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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Liver stiffness can predict decompensation and need for beta-blockers in compensated cirrhosis: a step beyond Baveno-VI criteria. Hepatol Int 2022; 16:89-98. [DOI: 10.1007/s12072-021-10280-w] [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: 09/14/2021] [Accepted: 11/12/2021] [Indexed: 11/30/2022]
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Metabolic Associated Fatty Liver Disease in Children-From Atomistic to Holistic. Biomedicines 2021; 9:biomedicines9121866. [PMID: 34944682 PMCID: PMC8698557 DOI: 10.3390/biomedicines9121866] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease has become the most common chronic liver disease in children due to the alarmingly increasing incidence of pediatric obesity. It is well-documented that MAFLD prevalence is directly related to an incremental increase in BMI. The multiple hits theory was designed for providing insights regarding the pathogenesis of steatohepatitis and fibrosis in MAFLD. Recent evidence suggested that the microbiome is a crucial contributor in the pathogenesis of MAFLD. Aside from obesity, the most common risk factors for pediatric MAFLD include male gender, low-birth weight, family history of obesity, MAFLD, insulin resistance, type 2 diabetes mellitus, obstructive sleep apnea, and polycystic ovarium syndrome. Usually, pediatric patients with MAFLD have nonspecific symptoms consisting of fatigue, malaise, or diffuse abdominal pain. A wide spectrum of biomarkers was proposed for the diagnosis of MAFLD and NASH, as well as for quantifying the degree of fibrosis, but liver biopsy remains the key diagnostic and staging tool. Nevertheless, elastography-based methods present promising results in this age group as potential non-invasive replacers for liver biopsy. Despite the lack of current guidelines regarding MAFLD treatment in children, lifestyle intervention was proven to be crucial in the management of these patients.
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Selvaraj EA, Mózes FE, Jayaswal ANA, Zafarmand MH, Vali Y, Lee JA, Levick CK, Young LAJ, Palaniyappan N, Liu CH, Aithal GP, Romero-Gómez M, Brosnan MJ, Tuthill TA, Anstee QM, Neubauer S, Harrison SA, Bossuyt PM, Pavlides M. Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD: A systematic review and meta-analysis. J Hepatol 2021; 75:770-785. [PMID: 33991635 DOI: 10.1016/j.jhep.2021.04.044] [Citation(s) in RCA: 194] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 03/15/2021] [Accepted: 04/25/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). METHODS PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. RESULTS We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. CONCLUSIONS When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. LAY SUMMARY Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.
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Affiliation(s)
- Emmanuel Anandraj Selvaraj
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK
| | - Ferenc Emil Mózes
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Arjun Narayan Ajmer Jayaswal
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Mohammad Hadi Zafarmand
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Yasaman Vali
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Jenny A Lee
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Christina Kim Levick
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Liam Arnold Joseph Young
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Naaventhan Palaniyappan
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Chang-Hai Liu
- UCM Digestive Diseases. Virgen del Rocio University Hospital. Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain; Center for Infectious Diseases, West China Hospital of Sichuan University; Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Guruprasad Padur Aithal
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Manuel Romero-Gómez
- UCM Digestive Diseases. Virgen del Rocio University Hospital. Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain
| | - M Julia Brosnan
- Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA
| | | | - Quentin M Anstee
- Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Stefan Neubauer
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Stephen A Harrison
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Patrick M Bossuyt
- Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, The Netherlands
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust and the University of Oxford, Oxford, UK.
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Mohamed MS, Youssef TM, Abdullah EE, Ahmed AE. Correlation between adiponectin level and the degree of fibrosis in patients with non-alcoholic fatty liver disease. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00134-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases, particularly in Egypt. It is defined as the accumulation of lipids inside the hepatocytes, in the absence of other etiologies of hepatic damage. It is frequently associated with obesity, diabetes mellitus, and metabolic syndrome. Adiponectin is an abundant adipocyte-derived protein with well-established anti-atherogenic, insulin-sensitizing, and anti-inflammatory properties. The liver is a major target organ for adiponectin especially in fatty liver diseases, and this adipocytokine has the ability to control many liver functions including metabolism, inflammation, and fibrosis. In this study, we aimed to find out the correlation between the degree of liver fibrosis in NAFLD patients and their serum adiponectin level as a future non-invasive method for the assessment of liver fibrosis to substitute liver biopsy to avoid its hazardous complication and also to study the correlation between diabetes mellitus as well as obesity and serum adiponectin level.
Results
Fifty patients were selected to participate in our study based on our inclusion criteria. They were recruited from the Internal Medicine Department, Gastroenterology Clinic in Al-Demerdash Hospital using a convenient sampling method. Diagnosis of NAFLD was confirmed by laboratory markers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid profile, ultrasound, and FibroScan examination. Analyzing the adiponectin levels showed that besides its significant correlation with body mass index (BMI), hypertension, diabetes mellitus, and dyslipidemia, it was significantly lower in the high-grade fibrosis group compared to the low-grade fibrosis group with a P-value of (0.000) and a cutoff value for stage 3/4 fibrosis of about 2.31 μg/ml which marked a promising hope of adiponectin being of protective value against liver fibrosis.
Conclusion
Both serum levels and hepatic adiponectin receptor expression are decreased in NAFLD. Therefore, either adiponectin itself or adiponectin-inducing agents might be of key therapeutic interest in the near future in the treatment of NAFLD.
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Trindade AJ, Thaniyavarn T, Hashemi N, Coppolino A, Kennedy JC, Mallidi HR, El-Chemaly S, Goldberg HJ. 1-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease. ERJ Open Res 2021; 7:00103-2021. [PMID: 34435032 PMCID: PMC8381158 DOI: 10.1183/23120541.00103-2021] [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: 02/10/2021] [Accepted: 05/13/2021] [Indexed: 11/09/2022] Open
Abstract
Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [
1] However, whether fatty liver disease with mild–moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown. We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015 and 2017 to identify whether patients with mild–moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3–F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (α=0.05, β=0.8). Secondary outcomes included index intensive care unit (ICU)-free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8–12 ng·mL−1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions and infection. 150 patients underwent lung transplantation between 2015 and 2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5–19.5 versus 12 days, IQR 0–18.0, p=0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture. This study demonstrates that mild–moderate severity NAFLD may not be a contraindication to lung transplantation. In this single-centre, retrospective analysis of lung transplant recipients, we identified that mild–moderate non-alcoholic fatty liver disease is associated with acceptable perioperative and 1-year outcomeshttps://bit.ly/36WNzhi
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Affiliation(s)
- Anil J Trindade
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.,Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Tany Thaniyavarn
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Nikroo Hashemi
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Antonio Coppolino
- Division of Thoracic Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - John C Kennedy
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Hari R Mallidi
- Division of Thoracic Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.,Division of Cardiac Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Souheil El-Chemaly
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
| | - Hilary J Goldberg
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
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Zhou YJ, Gao F, Liu WY, Wong GLH, Mahadeva S, Raihan Nik Mustapha N, Wang XD, Chan WK, Wong VWS, Zheng MH. Screening for compensated advanced chronic liver disease using refined Baveno VI elastography cutoffs in Asian patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2021; 54:470-480. [PMID: 34152626 DOI: 10.1111/apt.16487] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/07/2021] [Accepted: 06/04/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recently, Papatheodoridi et al proposed to refine the Baveno VI elastography dual-cutoffs and introduce an algorithm for the detection of compensated advanced chronic liver disease (cACLD) in asymptomatic European patients with chronic liver diseases. AIMS To validate the performance of the dual-cutoffs (8/12 kPa) and the proposed algorithm to identify patients with cACLD in three well-characterised Asian nonalcoholic fatty liver disease (NAFLD) cohorts. METHODS We included 830 patients with biopsy-proven NAFLD. Liver stiffness was measured using transient elastography (FibroScan). RESULTS cACLD was found in 21.8% of patients. Compared with the original Baveno VI elastography criteria (10/15 kPa), the new cutoffs showed a comparable specificity and a higher sensitivity for identifying cACLD. We developed a simplified risk model incorporating age, liver stiffness value, and platelet count, which outperformed liver stiffness measurement alone in two Chinese cohorts (P = 0.001), and was further validated in a Malaysian cohort (P = 0.04). Overall, the "two-step" screening of cACLD improved classification rates from 73.5% by the original dual-cutoffs to 86.7%. Notably, usage of our simplified risk model resulted in significantly lower false-negative rate than the refined screening approach by Papatheodoridi et al (27.1% vs 41.4%; P = 0.01). CONCLUSIONS The dual elastography cutoffs of 8 and 12 kPa are more appropriate to identify cACLD in Asian patients with NAFLD. In combination with a simplified risk model in unclassified patients, the two-step approach showed a classification rate of about 85%.
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Alam MS, Kamrul-Hasan ABM, Kalam ST, Rahman SMM, Hoque MI, Islam MB, Paul AK. Liver Stiffness Measurement by Using Transient Elastography in Bangladeshi Patients with Type 2 Diabetes Mellitus and Ultrasonography-Diagnosed Nonalcoholic Fatty Liver Disease. Diabetes Metab Syndr Obes 2021; 14:3089-3096. [PMID: 34262313 PMCID: PMC8273900 DOI: 10.2147/dmso.s317876] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/22/2021] [Indexed: 12/17/2022] Open
Abstract
PURPOSE Type 2 diabetes mellitus (T2DM) is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD), and the presence of T2DM tremendously drives NAFLD progression. The use of transient elastography (TE) for assessment of NAFLD has been increasing due to its high sensitivity and specificity. This study aimed to measure liver stiffness in patients with T2DM and ultrasonography (USG)-diagnosed NAFLD and assess the correlations between liver stiffness and other clinical and biochemical parameters. PATIENTS AND METHODS This cross-sectional study assessed 205 adult patients with T2DM and USG-diagnosed NAFLD who were being treated at a specialized endocrine private practice in Bangladesh. All subjects underwent TE for hepatic fibrosis assessment, which was performed using a FibroScan® 402 device. A fibrosis score ≥9.7 kilopascals (kPa) was used to define advanced fibrosis (≥F3). RESULTS Out of 205 (65.9% female, mean age 45 ± 27 years, 67.3% obese) patients, the frequencies of Grade 1, Grade 2, and Grade 3 fatty liver on USG were 46.3%, 51.2%, and 2.4%, respectively. According to the TE results, 41 (20%) had advanced fibrosis (≥F3). Subjects with advanced fibrosis had a higher body mass index (BMI), higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and higher frequencies of individuals with elevated ALT and AST and advanced fatty liver grades on USG. The fibrosis score (kPa) was strongly and positively correlated with age, BMI, waist circumference, obesity, serum ALT and AST levels, and the fatty liver grade in USG; the AST:ALT ratio did not correlate with kPa. CONCLUSION The data showed that 20% of the subjects with T2DM having NAFLD on USG exhibited advanced fibrosis, demonstrating the need for early diagnosis and treatment of NAFLD in T2DM. The use of TE with other serum markers can be helpful for the diagnosis of advanced fibrosis.
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Affiliation(s)
| | - A B M Kamrul-Hasan
- Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
| | - Syeda Tanzina Kalam
- Department of Psychiatry, Comilla Medical College Hospital, Comilla, Bangladesh
| | - S M Mizanur Rahman
- Department of Medicine, CMH and Army Medical College, Comilla, Bangladesh
| | | | - Md Belalul Islam
- Department of Medicine, Comilla Medical College, Comilla, Bangladesh
| | - Ajit Kumar Paul
- Department of Endocrinology, Maynamati Medical College, Comilla, Bangladesh
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Llop E, Iruzubieta P, Perelló C, Fernández Carrillo C, Cabezas J, Escudero MD, González M, Hernández Conde M, Puchades L, Arias-Loste MT, Serra MÁ, Crespo J, Calleja JL. High liver stiffness values by transient elastography related to metabolic syndrome and harmful alcohol use in a large Spanish cohort. United European Gastroenterol J 2021; 9:892-902. [PMID: 34077628 PMCID: PMC8498397 DOI: 10.1002/ueg2.12109] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/03/2021] [Indexed: 12/31/2022] Open
Abstract
Background and Aims Transient elastography (TE) to estimate liver stiffness has proved to be very useful in the diagnosis of chronic liver disease. Here, we intend to evaluate its use in a large Spanish cohort. Method Nested study within the PREVHEP‐ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) population‐based, cross‐sectional study performed between July 2015 and April 2017. An epidemiological questionnaire, laboratory tests and TE and anthropometric measurements were obtained. Results Data from 11,440 subjects were analyzed. Mean age was 50.3 (SD 12.4), of which 58.1% were women. 15.4% showed metabolic syndrome (NCEP ATP‐III), 1.3% were positive for hepatitis C antibodies, 0.8% positive for HBsAg, 9.1% reported harmful use of alcohol. The prevalence of significant fibrosis (LSM > 8 kPa), suggestive compensated advanced chronic liver disease (cACLD) (LSM ≥ 10 kPa) and highly suggestive cACLD (LSM > 15 kPa) was 5.6%, 2.9%, and 1.2% respectively. Risk factors associated with significant fibrosis were age (OR 1.03 [1.02–1.04; p < 0.001]), sex (OR 0.8 [0.6–0.95; p = 0.02]), AST (OR 1.01 [1.01–1.02; p < 0.001]), GGT (OR 1.005 [1.003–1.006; p < 0.001]) and metabolic syndrome (OR 2.1 [1.7–2.6; p < 0.001]); risk factors associated with suggestive cACLD were age (OR 1.04 [1.02–1.05; p < 0.001]), AST (OR 1.01 [1.01–1.02; p < 0.001]), GGT (OR 1.006 [1.004–1.008; p < 0.001]), low platelets (OR 0.997 [0.994–0.999; p = 0.02]) and metabolic syndrome (OR 2.2 [1.6–2.9; p < 0.001]); and risk factors associated with highly suggestive cACLD were age (OR 1.04 [1.02–1.06; p = 0.001]), AST (OR 1.02 [1.01–1.03; p < 0.001]), GGT (OR 1.005 [1.003–1.007; p < 0.001]), low platelets (OR 0.993 [0.989–0.997; p < 0.001]), metabolic syndrome (OR 2.1 [1.4–3.3; p = 0.001]) and alcohol consumption (OR 1.8 [1.05–3.1; p = 0.03]). A non‐negligible proportion of patients with normal transaminase levels, even with healthy transaminase levels, showed significant fibrosis and suggestive and highly suggestive cACLD 4.6% (95% CI 2.4–3.0), 2.1% (95% CI 1.9–2.5) and 1% (95% CI 0.7–1.1), respectively. Conclusion We found high proportion of significant fibrosis and cACLD measured by TE. The most relevant factor associated with significant fibrosis was metabolic syndrome, however TE is still an imperfect method since it overestimated the fibrosis stage in 50% of the histologically analyzed subjects.
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Affiliation(s)
- Elba Llop
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Puerta de Hierro Health Research Institute (IDIPHIM), CIBERhd, Majadahonda, Spain
| | - Paula Iruzubieta
- Department of Gastroenterology and Hepatology, Marqués de Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Christie Perelló
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Puerta de Hierro Health Research Institute (IDIPHIM), CIBERhd, Majadahonda, Spain
| | - Carlos Fernández Carrillo
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Puerta de Hierro Health Research Institute (IDIPHIM), CIBERhd, Majadahonda, Spain
| | - Joaquín Cabezas
- Department of Gastroenterology and Hepatology, Marqués de Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | | | - Marta González
- Department of Gastroenterology and Hepatology, Marqués de Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Marta Hernández Conde
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Puerta de Hierro Health Research Institute (IDIPHIM), CIBERhd, Majadahonda, Spain.,Department of Gastroenterology and Hepatology, Marqués de Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain.,Department of Gastroenterology and Hepatology, Hospital Clínic-La Malvarrosa, Valencia, Spain
| | - Laura Puchades
- Department of Gastroenterology and Hepatology, Hospital Clínic-La Malvarrosa, Valencia, Spain
| | - María Teresa Arias-Loste
- Department of Gastroenterology and Hepatology, Marqués de Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Miguel Ángel Serra
- Department of Gastroenterology and Hepatology, Hospital Clínic-La Malvarrosa, Valencia, Spain
| | - Javier Crespo
- Department of Gastroenterology and Hepatology, Marqués de Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - José Luis Calleja
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro, Puerta de Hierro Health Research Institute (IDIPHIM), CIBERhd, Majadahonda, Spain
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Thong VD, Quynh BTH. Correlation of Serum Transaminase Levels with Liver Fibrosis Assessed by Transient Elastography in Vietnamese Patients with Nonalcoholic Fatty Liver Disease. Int J Gen Med 2021; 14:1349-1355. [PMID: 33889015 PMCID: PMC8057835 DOI: 10.2147/ijgm.s309311] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 03/23/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a cause of chronic liver disease, often resulting in liver cirrhosis, portal hypertension, and hepatocellular carcinoma damaging outcomes. Alanine transaminase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury. Several studies have demonstrated that high ALT levels are correlated with higher nonalcoholic steatohepatitis (NASH) risk. The aim was to determine the correlation of serum alanine aminotransferase and aspartate transaminase with liver stiffness in Vietnamese patients with NAFLD. PATIENTS AND METHODS The study included 18 to 80 years old patients diagnosed with fatty liver on ultrasound at the University of Medical Center (UMC) liver clinic. Liver stiffness was measured using transient elastography. The histopathological, demographic, and laboratory data of the participants were also collected. The baseline and clinical characteristics of NAFLD patients were stratified by serum ALT levels. RESULTS There were 138 NAFLD patients, including 82 men (59.4%) and 56 women (40.6%) (mean ± SD age of 41 ± 11 years). Liver fibrosis (F0) between the two groups showed no significant difference (p = 0.469). Similarly, no difference was found in the mild fibrosis level (F2) of the two groups of patients (p = 0.371). ALT level was significantly higher in NAFLD patients with advanced fibrosis (F3, F4) (3.2% vs 15.9%, p = 0.0013; 3.2% vs 13.2%, p = 0.0047, respectively). NAFLD patients with mild to moderate fibrosis (F1-F2) were detected at 59 U/L cut-off value with 67% sensitivity and 51% specificity. However, severe fibrosis and/or cirrhosis patients (F3-F4) had a cut-off value of 81 U/L with 53% sensitivity and 67% specificity in patients. CONCLUSION Using ALT level as a marker for severe NAFLD would consider high-risk patients as mild cases, even though there is still the risk of progressive and severe hepatic disease. Our study underlines the small contribution of ALT as an independent factor for detecting NAFLD severity.
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Affiliation(s)
- Vo Duy Thong
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
- Department of Gastroenterology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Bui Thi Huong Quynh
- Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
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Mikolasevic I, Stojsavljevic S, Blazic F, Mijic M, Radic-Kristo D, Juric T, Skenderevic N, Klapan M, Lukic A, Filipec Kanizaj T. Noninvasive markers of liver steatosis and fibrosis after liver transplantation - Where do we stand? World J Transplant 2021; 11:37-53. [PMID: 33816145 PMCID: PMC8009059 DOI: 10.5500/wjt.v11.i3.37] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/10/2020] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
In the last two decades, advances in immunosuppressive regimens have led to fewer complications of acute rejection crisis and consequently improved short-term graft and patient survival. In parallel with this great success, long-term post-transplantation complications have become a focus of interest of doctors engaged in transplant medicine. Metabolic syndrome (MetS) and its individual components, namely, obesity, dyslipidemia, diabetes, and hypertension, often develop in the post-transplant setting and are associated with immuno-suppressive therapy. Nonalcoholic fatty liver disease (NAFLD) is closely related to MetS and its individual components and is the liver manifestation of MetS. Therefore, it is not surprising that MetS and its individual components are associated with recurrent or "de novo" NAFLD after liver transplantation (LT). Fibrosis of the graft is one of the main determinants of overall morbidity and mortality in the post-LT period. In the assessment of post-LT steatosis and fibrosis, we have biochemical markers, imaging methods and liver biopsy. Because of the significant economic burden of post-LT steatosis and fibrosis and its potential consequences, there is an unmet need for noninvasive methods that are efficient and cost-effective. Biochemical scores can overestimate fibrosis and are not a good method for fibrosis evaluation in liver transplant recipients due to frequent post-LT thrombocytopenia. Transient elastography with controlled attenuation parameter is a promising noninvasive method for steatosis and fibrosis. In this review, we will specifically focus on the evaluation of steatosis and fibrosis in the post-LT setting in the context of de novo or recurrent NAFLD.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia; Department of Gastroenterology, Clinical hospital Merkur, Zagreb, Croatia; Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sanja Stojsavljevic
- Department of Gastroenterology, University Hospital Center “Sestre Milosrdnice”, Zagreb 10000, Croatia
| | - Filip Blazic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Maja Mijic
- Department of Gastroenterology, University Hospital Merkur, Zagreb 10000, Croatia
| | - Delfa Radic-Kristo
- Department of Hematology, University Hospital Merkur, Zagreb, Croatia; Faculty of Medicine, University of Zagreb, Zagreb, Croatia
| | - Toni Juric
- School of Medicine, School of Medicine, Rijeka 51000, Croatia
| | - Nadija Skenderevic
- Department of Gastroenterology, University Hospital Merkur, Zagreb 10000, Croatia
| | - Mia Klapan
- School of Medicine, School of Medicine, Rijeka 51000, Croatia
| | - Andjela Lukic
- School of Medicine, School of Medicine, Rijeka 51000, Croatia
| | - Tajana Filipec Kanizaj
- Department of Gastroenterology, University Hospital Merkur, Zagreb, Croatia; Faculty of Medicine, University of Zagreb, Zagreb, Croatia
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Oeda S, Tanaka K, Oshima A, Matsumoto Y, Sueoka E, Takahashi H. Diagnostic Accuracy of FibroScan and Factors Affecting Measurements. Diagnostics (Basel) 2020; 10:diagnostics10110940. [PMID: 33198092 PMCID: PMC7696616 DOI: 10.3390/diagnostics10110940] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/10/2020] [Accepted: 11/11/2020] [Indexed: 12/12/2022] Open
Abstract
Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is qualitative and subjective. The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) determined using FibroScan are the evidence-based non-invasive measures of liver fibrosis and steatosis, respectively. The LSM and CAP measurements are carried out simultaneously, and the median values of more than ten valid measurements are used to quantify liver fibrosis and steatosis. Here, we demonstrate that the reliability of the LSM depends on the interquartile range to median ratio (IQR/Med), but CAP values do not depend on IQR/Med. In addition, the LSM is affected by inflammation, congestion, and cholestasis in addition to fibrosis, while CAP values are affected by the body mass index in addition to steatosis. We also show that the M probe provides higher LSM values but lower CAP values than the XL probe in the same population. However, there was no statistically significant difference between the diagnostic accuracies of the two probes. These findings are important to understand the reliability of FibroScan measurements and the factors influencing measurement values for all patients.
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Affiliation(s)
- Satoshi Oeda
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan;
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan; (A.O.); (Y.M.); (E.S.)
- Correspondence:
| | - Kenichi Tanaka
- Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan;
| | - Ayaka Oshima
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan; (A.O.); (Y.M.); (E.S.)
| | - Yasue Matsumoto
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan; (A.O.); (Y.M.); (E.S.)
| | - Eisaburo Sueoka
- Department of Laboratory Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan; (A.O.); (Y.M.); (E.S.)
- Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, Japan;
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Lupsor-Platon M, Serban T, Silion AI, Tirpe A, Florea M. Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease: A Step Forward for Better Evaluation Using Ultrasound Elastography. Cancers (Basel) 2020; 12:cancers12102778. [PMID: 32998257 PMCID: PMC7601664 DOI: 10.3390/cancers12102778] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 09/15/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Non-alcoholic fatty liver disease (NAFLD) attracts a lot of attention, due to the increasing prevalence and progression to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Consequently, new non-invasive, cost-effective diagnostic methods are needed. This review aims to explore the diagnostic performance of ultrasound (US) elastography in NAFLD and NAFLD-related HCC, adding a new dimension to the conventional US examination—the liver stiffness quantification. The vibration controlled transient elastography (VCTE), and 2D-Shear wave elastography (2D-SWE) are effective in staging liver fibrosis in NAFLD. VCTE presents the upside of assessing steatosis through the controlled attenuation parameter. Hereby, we critically reviewed the elastography techniques for the quantitative characterization of focal liver lesions (FLLs), focusing on HCC: Point shear wave elastography and 2D-SWE. 2D-SWE presents a great potential to differentiate malignant from benign FLLs, guiding the clinician towards the next diagnostic steps. As a disease-specific surveillance tool, US elastography presents prognostic capability, improving the NAFLD-related HCC monitoring. Abstract The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population prompts for a quick response from physicians. As NAFLD can progress to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC), new non-invasive, rapid, cost-effective diagnostic methods are needed. In this review, we explore the diagnostic performance of ultrasound elastography for non-invasive assessment of NAFLD and NAFLD-related HCC. Elastography provides a new dimension to the conventional ultrasound examination, by adding the liver stiffness quantification in the diagnostic algorithm. Whilst the most efficient elastographic techniques in staging liver fibrosis in NAFLD are vibration controlled transient elastography (VCTE) and 2D-Shear wave elastography (2D-SWE), VCTE presents the upside of assessing steatosis through the controlled attenuation parameter (CAP). Hereby, we have also critically reviewed the most important elastographic techniques for the quantitative characterization of focal liver lesions (FLLs), focusing on HCC: Point shear wave elastography (pSWE) and 2D-SWE. As our paper shows, elastography should not be considered as a substitute for FLL biopsy because of the stiffness values overlap. Furthermore, by using non-invasive, disease-specific surveillance tools, such as US elastography, a subset of the non-cirrhotic NAFLD patients at risk for developing HCC can be detected early, leading to a better outcome. A recent ultrasomics study exemplified the wide potential of 2D-SWE to differentiate benign FLLs from malignant ones, guiding the clinician towards the next steps of diagnosis and contributing to better long-term disease surveillance.
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Affiliation(s)
- Monica Lupsor-Platon
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Correspondence:
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.S.); (A.-I.S.); (A.T.)
| | - Alexandra-Iulia Silion
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.S.); (A.-I.S.); (A.T.)
| | - Alexandru Tirpe
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.S.); (A.-I.S.); (A.T.)
| | - Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400001 Cluj-Napoca, Romania;
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Puthenpura MM, Patel V, Fam J, Katz L, Tichansky DS, Myers S. The Use of Transient Elastography Technology in the Bariatric Patient: a Review of the Literature. Obes Surg 2020; 30:5108-5116. [PMID: 32981002 DOI: 10.1007/s11695-020-05002-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/17/2020] [Accepted: 09/22/2020] [Indexed: 12/17/2022]
Abstract
Transient elastography (TE) is a non-invasive technology that demonstrates promise in assessing liver steatosis and fibrosis without the risks of traditional percutaneous liver biopsy. Many studies have examined its reliability in respect to liver biopsy, but fewer have examined using TE in obese and bariatric surgery patients. With evidence showing that bariatric surgery can lead to improvement of liver steatosis and fibrosis, TE has the potential to provide a simple avenue of hepatic assessment in patients before and after procedures. This review article investigates what is known about the reliability of TE and its implementation in obese and bariatric surgery patients.
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Affiliation(s)
- Max M Puthenpura
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.
| | - Vishal Patel
- The Center for Liver Disease, Tower Health Transplant Institute, 420 S 5th Ave, West Reading, PA, 19611, USA
| | - John Fam
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
| | - Leon Katz
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
| | - David S Tichansky
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
| | - Stephan Myers
- Department of Surgery, Drexel University College of Medicine, 2900 W Queen Lane, Philadelphia, PA, 19129, USA.,Tower Health Weight Loss Surgery and Wellness Center, 1220 Broadcasting Rd, Wyomissing, PA, 19610, USA
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Nguyen TH, Wardell R, Chitturi S, Teoh N, Farrell G. When the liver gets stiff, the tough get moving. J Gastroenterol Hepatol 2020; 35:953-959. [PMID: 31867782 DOI: 10.1111/jgh.14963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 12/20/2019] [Indexed: 12/30/2022]
Abstract
Liver stiffness measurement (LSM) by FibroScan-determined transient elastography is a noninvasive approach to estimate liver fibrosis severity. In non-alcoholic fatty liver disease (NAFLD), advanced liver fibrosis is excluded by normal liver stiffness, but a wide range of cutoffs have been used to predict advanced liver fibrosis or cirrhosis. This may be partly because steatosis (measured by controlled attenuation parameter [CAP]) contributes to liver stiffness and also because LSM fluctuates in NAFLD. In a recent pivotal study, one-third of patients with liver stiffness > 12.0 kPa showed reversal after 4-6 months; these cases did not have advanced liver fibrosis on biopsy. We performed serial FibroScans 6-36 months apart in 73 NAFLD patients, 38 with LSM > 10 kPa at entry. Those who lost ≥ 1 kg of weight (n = 31) significantly reduced liver stiffness (3.6 ± 6.1 vs 0.53 ± 4.1 kPa, P < 0.05) and CAP score (39 ± 63 dB/m of loss vs 24 ± 65 dB/m of gain, P < 0.05) compared with those who did not (n = 29). Patients who reported increased physical activity (n = 25) also reduced liver stiffness (3.6 ± 6 vs 0.35 ± 6 kPa) and CAP (20 ± 71 dB/m of loss vs 32 ± 71 dB/m of gain). Overall, those with improved LSM were significantly more likely to have lost weight and/or improved physical activity. These effects of lifestyle adjustments partly explain why a single measurement of 12.0 kPa is not a reliable cutoff for advanced liver fibrosis in NAFLD. In addition to repeating the study after 6-12 months, documentation of response to lifestyle advice and weight reduction should be determined before assuming any cutoff indicates advanced liver fibrosis. Despite this reservation about diagnostic accuracy, we consider that measurement of liver stiffness and CAP score serve to motivate patients to enact lifestyle modifications that can improve NAFLD severity.
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Affiliation(s)
- Thuy-Huong Nguyen
- Gastroenterology and Hepatology Unit, Canberra Hospital and Australian National University Medical School, Canberra, Australian Capital Territory, Australia
| | - Rebecca Wardell
- Gastroenterology and Hepatology Unit, Canberra Hospital and Australian National University Medical School, Canberra, Australian Capital Territory, Australia
| | - Shiv Chitturi
- Gastroenterology and Hepatology Unit, Canberra Hospital and Australian National University Medical School, Canberra, Australian Capital Territory, Australia
| | - Narci Teoh
- Gastroenterology and Hepatology Unit, Canberra Hospital and Australian National University Medical School, Canberra, Australian Capital Territory, Australia
| | - Geoff Farrell
- Gastroenterology and Hepatology Unit, Canberra Hospital and Australian National University Medical School, Canberra, Australian Capital Territory, Australia
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Fukuda T, Hamaguchi M, Osaka T, Hashimoto Y, Ushigome E, Asano M, Yamazaki M, Fukuda E, Yamaguchi K, Ogawa K, Goshima N, Fukui M. A Pilot Study on the Effect of Anti-Thrombopoietin Antibody on Platelet Count in Patients with Type 2 Diabetes. Molecules 2020; 25:molecules25071667. [PMID: 32260359 PMCID: PMC7181124 DOI: 10.3390/molecules25071667] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 03/28/2020] [Accepted: 04/03/2020] [Indexed: 12/20/2022] Open
Abstract
Thrombopoietin (THPO) is a circulatory cytokine that plays an important role in platelet production. The presence of anti-THPO antibody relates to thrombocytopenia and is rarely seen in hematopoietic and autoimmune diseases. To date, there had been no reports that focused on the anti-THPO antibody in patients with type 2 diabetes mellitus (T2DM). To evaluate prevalence of the anti-THPO antibody in patients with T2DM and the relationship between anti-THPO antibody and platelet count, a cross-sectional study was performed on 82 patients with T2DM. The anti-THPO antibody was measured by ELISA using preserved sera and detected in 13 patients. The average platelet count was significantly lower in patients with the anti-THPO antibody than in those without the anti-THPO antibody. Multivariate linear regression analyses showed a significant relationship between the anti-THPO antibody and platelet count, after adjusting for other variables. To our best knowledge, this was the first report on the effect of the anti-THPO antibody on platelet count in patients with T2DM. Further investigation is needed to validate the prevalence and pathological significance of the anti-THPO antibody in patients with T2DM.
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Affiliation(s)
- Takuya Fukuda
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
- Correspondence: ; Tel.: +81-75-251-5505
| | - Takafumi Osaka
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
- Department of Endocrinology and Diabetology, Ayabe City Hospital, Ayabe 623-0011, Japan
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
| | - Emi Ushigome
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
| | - Mai Asano
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
| | - Masahiro Yamazaki
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
| | - Eriko Fukuda
- Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan; (E.F.); (K.Y.); (N.G.)
- ProteoBridge Corporation, Tokyo 135-0064, Japan;
| | - Kei Yamaguchi
- Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan; (E.F.); (K.Y.); (N.G.)
- ProteoBridge Corporation, Tokyo 135-0064, Japan;
| | - Koji Ogawa
- ProteoBridge Corporation, Tokyo 135-0064, Japan;
| | - Naoki Goshima
- Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan; (E.F.); (K.Y.); (N.G.)
- ProteoBridge Corporation, Tokyo 135-0064, Japan;
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan; (T.F.); (T.O.); (Y.H.); (E.U.); (M.A.); (M.Y.); (M.F.)
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Arterial stiffness is associated independently with liver stiffness in biopsy-proven nonalcoholic fatty liver disease: a transient elastography study. Eur J Gastroenterol Hepatol 2020; 32:54-57. [PMID: 31290769 DOI: 10.1097/meg.0000000000001471] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased arterial stiffness. However, the question as to whether an association exists between the extent of vascular and liver stiffness in patients with biopsy-proven NAFLD remains open. In this study, we sought to investigate whether pulse wave velocity (PWV) and augmentation index (AIx) - two common indices of arterial stiffness - are associated with (a) liver stiffness measurement (LSM) on transient elastography (TE) and (b) histological liver fibrosis. PATIENTS AND METHODS We examined 125 patients with biopsy-proven NAFLD and 55 age-matched and sex-matched controls. Arterial stiffness of the brachial artery was measured using a Mobil-O-Graph arteriography system. LSM was assessed using TE, whereas the presence of advanced fibrosis (F ≥ 3) was determined on histology. RESULTS Patients with NAFLD had higher PWV [median: 7.2 (6.3-8.2) and 6.2 (5.5-6.7) m/s, respectively, P < 0.001] and AIx (mean: 21.3 ± 13.5 and 17.2 ± 11.9%, respectively, P=0.01) compared with the controls. LSM showed positive correlations with both PWV (ρ = 0.300; P<0.01) and AIx (ρ = 0.223, P = 0.02). Both indices of arterial stiffness were higher in patients with advanced fibrosis than in those with nonadvanced fibrosis (F ≤ 2). CONCLUSION The severity of arterial and liver stiffness increases in parallel in patients with biopsy-proven NAFLD. Systematic risk assessment for reducing arterial stiffness is recommended in the presence of TE-determined advanced fibrosis.
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Kim SU, Jeon MY, Lim TS. Diagnostic Performance of Serum Asialo-α1-acid Glycoprotein for Advanced Liver Fibrosis or Cirrhosis in Patients with Chronic Hepatitis B or Nonalcoholic Fatty Liver Disease. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2019; 74:341-348. [PMID: 31870140 DOI: 10.4166/kjg.2019.74.6.341] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/09/2019] [Accepted: 08/13/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS The utility of asialo-α1-acid glycoprotein (AsAGP) for assessing the fibrotic burden is unknown. This study examined the diagnostic performance of the AsAGP level for advanced liver fibrosis or cirrhosis in patients with chronic hepatitis B (CHB) or nonalcoholic fatty liver disease (NAFLD). METHODS From July to December 2018, 48 patients with CHB and 75 with NAFLD were recruited prospectively. Transient elastography was used as the reference standard for liver fibrosis, and the cutoff liver stiffness values were defined as 10.0 kilopascal (kPa) for ≥F3 and 12.0 kPa for F4 in CHB patients, and 9.0 kPa for ≥F3 and 11.8 kPa for F4 in NAFLD patients. RESULTS To predict stage ≥F3 and F4 fibrosis, the areas under the receiver operating characteristic curves of the AsAGP level in patients with CHB were 0.788 (95% CI 0.647-0.930; p=0.005) and 0.825 (95% CI 0.674-0.976; p=0.004), respectively. The cutoff AsAGP levels in patients with CHB that maximized the sum of the sensitivity and specificity values were 1.31 (sensitivity 100.0%, specificity 52.6%) and 1.55 (sensitivity 75.0%, specificity 80.0%), respectively. In contrast, the AsAGP level was similar regardless of the fibrosis stage in patients with NAFLD (all p>0.05 between the stages). CONCLUSIONS The AsAGP level showed acceptable diagnostic accuracy in predicting advanced liver fibrosis and cirrhosis in patients with CHB but not in those with NAFLD. Further studies will be needed to validate the diagnostic performance of the AsAGP level in patients with NALFD.
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Mi Young Jeon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Zhang X, Wong GLH, Wong VWS. Application of transient elastography in nonalcoholic fatty liver disease. Clin Mol Hepatol 2019; 26:128-141. [PMID: 31696690 PMCID: PMC7160347 DOI: 10.3350/cmh.2019.0001n] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 09/25/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend non-invasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.
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Affiliation(s)
- Xinrong Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol 2019; 16:517-530. [PMID: 31278377 DOI: 10.1038/s41575-019-0169-z] [Citation(s) in RCA: 195] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/04/2019] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in children and adolescents. Over the past 5 years, developments have revolutionized our understanding of the genetic factors, natural history, diagnostic modalities and therapeutic targets for this disease. New polymorphisms, such as those in PNPLA3, TM6SF2, MBOAT7 and GCKR, have been identified and used to predict the development and severity of NAFLD in both adults and children, and their interaction with environmental factors has been elucidated. Studies have demonstrated the true burden of paediatric NAFLD and its progression to end-stage liver disease in adulthood. In particular, nonalcoholic steatohepatitis can progress to advanced fibrosis and cirrhosis, emphasizing the importance of early diagnosis. Non-invasive imaging tests, such as transient elastography, will probably replace liver biopsy for the diagnosis of nonalcoholic steatohepatitis and the assessment of fibrosis severity in the near future. The therapeutic landscape is also expanding rapidly with the development of drugs that can modify liver steatosis, inflammation and fibrosis, indicating that pharmacotherapy for NAFLD will become available in the future. In this Review, we summarize current knowledge and new advances related to the pathogenesis and management of paediatric NAFLD.
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Draijer L, Benninga M, Koot B. Pediatric NAFLD: an overview and recent developments in diagnostics and treatment. Expert Rev Gastroenterol Hepatol 2019; 13:447-461. [PMID: 30875479 DOI: 10.1080/17474124.2019.1595589] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults in industrialized countries. Besides liver-related morbidity, NAFLD is also associated with an increased risk of cardiovascular disease, type 2 diabetes and mortality at adult age. However, despite the high prevalence and serious complications, diagnosing and staging of disease remains complicated due to a lack of accurate screening tools and non-invasive methods to detect fibrosis. Areas covered: Recent insights in epidemiology, pathogenesis, diagnostic evaluation and treatment options in pediatric NAFLD are being reviewed, with a particular focus on new developments in diagnostic tools. Expert opinion: Due to their long life span, children with NAFLD are particularly at risk of complications in their lifetime. Therefore, an effective screening strategy for children to identify those with NAFLD at risk of complications is urgently needed. This is further underscored by new pharmacological therapies that are expected to become available in the next 5 years. Momentarily no accurate non-invasive method for diagnosing pediatric NAFLD is available. New promising biomarkers and imaging tools could hopefully provide better screening tools and could contribute to the development of a successful management plan to identify children with NAFLD.
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Affiliation(s)
- Laura Draijer
- a Department of Pediatric Gastroenterology and Nutrition , Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital , Amsterdam , The Netherlands
| | - Marc Benninga
- a Department of Pediatric Gastroenterology and Nutrition , Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital , Amsterdam , The Netherlands
| | - Bart Koot
- a Department of Pediatric Gastroenterology and Nutrition , Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital , Amsterdam , The Netherlands
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Shirokova EN, Pavlov CS, Karaseva AD, Alieva AM, Sedova AV, Ivashkin VT. Elastography in the Diagnosis of Non-Alcoholic Fatty Liver Disease. ANNALS OF THE RUSSIAN ACADEMY OF MEDICAL SCIENCES 2019; 74:5-13. [DOI: 10.15690/vramn1071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Currently, there has been a progressive increase in prevalence of one of the most common diffuse chronic liver diseases ― non-alcoholic fatty liver disease (NAFLD). Assessment of the stages of liver fibrosis and steatosis is prognostically significant in diagnosis of NAFLD. Routine diagnostic methods are either not able to accurately assess the severity of fibrosis and steatosis (ultrasound, laboratory tests), or cannot be used as a simple screening tool (liver biopsy) due to such limitations as invasiveness, dependence on pathologist qualification, high cost, and limited region of interest. Over the last two decades, the great progress has been made in non-invasive visualization of pathological changes in liver diseases. In this review, we examined the diagnostic characteristics of the most widely used non-invasive imaging methods in clinical practice, available for quantitative determination of fat and fibrosis in the liver: transient elastography with controlled attenuation parameter (CAP), acoustic radiation force impulse (ARFI) and shear wave elastography (SWE). Comparing these methods and their limitations, we came to conclusion, that elastographic methods (slightly more ARFI and SWE) are able to verify the F3, F4 stages of fibrosis in NAFLD with high sensitivity and specificity (90%); however, they are less accurate for early stages. Elastographic techniques have moderate accuracy in identifying the degree of steatosis due to the lack of uniform standardized cut-off values of CAP.
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Safarian M, Mohammadpour S, Shafiee M, Ganji A, Soleimani A, Nematy M, Bahari A. Effect of diet-induced weight loss on cytokeratin-18 levels in overweight and obese patients with liver fibrosis. Diabetes Metab Syndr 2019; 13:989-994. [PMID: 31336557 DOI: 10.1016/j.dsx.2019.01.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 01/14/2019] [Indexed: 12/14/2022]
Abstract
AIMS Liver biopsy is currently the gold standard test for NAFLD diagnosis and staging but has many drawbacks. In addition, other tools such as transient elastography are limited to specialized research centers. To assess the usefulness of CK-18 as a non-invasive biomarker for detecting therapeutic responses in patients with liver fibrosis. MATERIALS AND METHODS Sixty overweight and obese patients with liver fibrosis were evaluated by a dietitian and given a weight-reducing diet with a calorie deficit of 500-1000 kcal/day over a 6-month period. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) both were performed at the beginning and at the end of the trial to determine liver steatosis and liver fibrosis, respectively. Serum CK-18 levels were measured by enzyme linked immune sorbent assay (ELISA) at baseline and at 3 and 6 months after intervention. RESULTS Patients experienced a rapid weight loss of -7.6 kg (8.5%) during the trial. Among all participants, liver steatosis decreased from 76.5 ± 12.2% to 51.8 ± 24.4% (baseline to end-point) (p < 0.001) and fibrosis score decreased from 9.9 ± 3.7 to 7.2 ± 2.4 (p < 0.001) (a 27.2% decrease). Serum CK-18 levels decreased from 290.2 ± 98.1 U/L to 217.6 ± 64.8 U/L (p < 0.001) (a 25.0% decrease). ΔCK-18 was found to be significantly associated with delta fibrosis score (r = 0.25, p = 0.05) CONCLUSIONS: This trial showed a significant positive association between changes in CK-18 levels and changes in liver fibrosis over a 6-month dietary intervention.
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Affiliation(s)
- Mohammad Safarian
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Sepideh Mohammadpour
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mojtaba Shafiee
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Azita Ganji
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Anvar Soleimani
- Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Nematy
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Bahari
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Hwang M, Piskunowicz M, Darge K. Advanced Ultrasound Techniques for Pediatric Imaging. Pediatrics 2019; 143:e20182609. [PMID: 30808770 PMCID: PMC6398363 DOI: 10.1542/peds.2018-2609] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/19/2018] [Indexed: 12/13/2022] Open
Abstract
Ultrasound has become a useful tool in the workup of pediatric patients because of the highly convenient, cost-effective, and safe nature of the examination. With rapid advancements in anatomic and functional ultrasound techniques over the recent years, the diagnostic and interventional utility of ultrasound has risen tremendously. Advanced ultrasound techniques constitute a suite of new technologies that employ microbubbles to provide contrast and enhance flow visualization, elastography to measure tissue stiffness, ultrafast Doppler to deliver high spatiotemporal resolution of flow, three- and four-dimensional technique to generate accurate spatiotemporal representation of anatomy, and high-frequency imaging to delineate anatomic structures at a resolution down to 30 μm. Application of these techniques can enhance the diagnosis of organ injury, viable tumor, and vascular pathologies at bedside. This has significant clinical implications in pediatric patients who are not easy candidates for lengthy MRI or radiation-requiring examination, and are also in need of a highly sensitive bedside technique for therapeutic guidance. To best use the currently available, advanced ultrasound techniques for pediatric patients, it is necessary to understand the diagnostic utility of each technique. In this review, we will educate the readers of emerging ultrasound techniques and their respective clinical applications.
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Affiliation(s)
- Misun Hwang
- Department of Radiology, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and
| | - Maciej Piskunowicz
- Department of Radiology, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and
- Department of Radiology, Medical University of Gdansk, Gdańsk, Poland
| | - Kassa Darge
- Department of Radiology, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and
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Jiang W, Huang S, Teng H, Wang P, Wu M, Zhou X, Ran H. Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis. BMJ Open 2018; 8:e021787. [PMID: 30139901 PMCID: PMC6112406 DOI: 10.1136/bmjopen-2018-021787] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 07/20/2018] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE This study aimed to assess the accuracy of staging liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) usingpoint shear wave elastography (pSWE) and transient elastography (TE). SETTING Relevant records on NAFLD were retrieved from PubMed, Embase, Web of Science and the China National Knowledge Infrastructure databases up to 20 December 2017. A bivariate mixed-effects model was conducted to combine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the summary receiver operating characteristic curve (AUC) between pSWE and TE. A sensitivity analysis was implemented to explore the source of heterogeneity. PARTICIPANTS Patients with NAFLD who had a liver stiffness measurement using pSWE and TE before liver biopsy were enrolled according to the following criteria: 2×2 contingency tables can be calculated via the reported number of cases; sensitivity and specificity were excluded according to the following criteria: history of other hepatic damage, such as chronic hepatitis C, concurrent active hepatitis B infection, autoimmune hepatitis, suspicious drug usage and alcohol abuse. RESULTS Nine pSWE studies comprising a total of 982 patients and 11 TE studies comprising a total of 1753 patients were included. For detection of significant fibrosis, advanced fibrosis and cirrhosis, the summary AUC was 0.86 (95% CI 0.83 to 0.89), 0.94 (95% CI 0.91 to 0.95) and 0.95 (95% CI 0.93 to 0.97) for pSWE, and the summary AUC was 0.85 (95% CI 0.82 to 0.88), 0.92 (95% CI 0.89 to 0.94) and 0.94 (95% CI 0.93 to 0.97) for TE, respectively. The proportion of failure measurement was over tenfold as common with TE using an M probe compared with pSWE. CONCLUSION pSWE and TE, providing precise non-invasive staging of liver fibrosis in NAFLD, are promising techniques, particularly for advanced fibrosis and cirrhosis.
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Affiliation(s)
- Weixi Jiang
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
| | - Sirun Huang
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
| | - Hua Teng
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
| | - Peipei Wang
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
| | - Meng Wu
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
| | - Xia Zhou
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
| | - Haitao Ran
- Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Ultrasound Department, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
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Abstract
NAFLD is a global epidemic. The prevalence of NAFLD is 20-30% in North America, northern Europe, Australia, Japan, India and China. It is crucial that patients with NAFLD receive an assessment for their risk of advanced fibrosis, which increases the risk of hepatocellular carcinoma and other complications of cirrhosis. Risk stratification that is efficient, cost-effective, patient-centred and evidence-based is one of the most important issues facing clinicians who care for those with liver disease. Given patients' preference to avoid liver biopsy, noninvasive alternatives to assess liver fibrosis are in high demand. The most accurate noninvasive methods are based on liver elastography. Research on these techniques - which include vibration-controlled transient elastography (VCTE), magnetic resonance elastography (MRE), shear-wave elastography and acoustic radiation force impulse - has proliferated. Unfortunately, the literature has not kept pace with clinical practice. There is limited guidance for how clinicians should anticipate and manage the pitfalls of these tests. Furthermore, guidance is unavailable for clinicians regarding the optimal incorporation of VCTE, MRE or the emerging elastographic techniques into their clinical strategy, particularly for patients with NAFLD. In this Review, we summarize the available evidence, highlight gaps to address in further research and explore optimization of these techniques in clinical practice.
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Alizadeh A, Mansour-Ghanaei F, Roozdar A, Joukar F, Sepehrimanesh M, Hojati SA, Mansour-Ghanaei A. Laboratory Tests, Liver Vessels Color Doppler Sonography, and FibroScan Findings in Patients with Nonalcoholic Fatty Liver Disease: An Observation Study. J Clin Imaging Sci 2018; 8:12. [PMID: 29692949 PMCID: PMC5894278 DOI: 10.4103/jcis.jcis_93_17] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2017] [Accepted: 02/13/2018] [Indexed: 12/13/2022] Open
Abstract
Objective Determination of the amount of parenchymal damage in nonalcoholic fatty liver disease (NAFLD) is crucial to choose the best treatment and management. Aim Here, the associations between laboratory data and severity of steatosis and fibrosis plus hepatic vessel Doppler indices in NAFLD patients were investigated. Patients and Methods Fifty patients (20 males and 30 females) with NAFLD criteria were enrolled. Fatty liver was graded by sonography (SGFL) and FibroScan (FGFL). In addition, liver fibrosis was graded through FGLF. Damages to the portal, hepatic, and splenic veins were evaluated by color Doppler/dopplex. Serum liver enzymes and C-reactive protein (CRP) were also measured. Results Significant association existed between SGFL and FGFL (P = 0.006). Portal vein pulsatility index (PI) and phasicity plus the triphasic and monophasic pattern of hepatic veins significantly associated with fatty liver grade evaluated by sonography. Splenic vein Peak systolic velocity and PI showed significant association with FGFL. Eventually, elevated liver enzymes and CRP significantly correlated with FGLF. Conclusion We found that the severity of fatty liver is correlated with hepatic and portal veins damages; however, the degree of parenchymal fibrosis was independent to these indices and can be directly evaluated by FGFL. In addition, elevated liver enzymes and CRP correlated with the degree of fibrosis.
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Affiliation(s)
- Ahmad Alizadeh
- Department of Radiology, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Ava Roozdar
- Department of Radiology, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Caspian Digestive Diseases Research Center, Guilan University of Medical Science, Rasht, Iran
| | - Masood Sepehrimanesh
- Gastrointestinal Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Seyedeh Amineh Hojati
- Caspian Digestive Diseases Research Center, Guilan University of Medical Science, Rasht, Iran
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Noureddin M, Wong MM, Todo T, Lu SC, Sanyal AJ, Mena EA. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals. World J Gastroenterol 2018; 24:1269-1277. [PMID: 29568207 PMCID: PMC5859229 DOI: 10.3748/wjg.v24.i11.1269] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Revised: 01/27/2018] [Accepted: 03/03/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. METHODS Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. RESULTS One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) (P < 0.05). Post-SVR, 48 patients (47.5%) had steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P < 0.05. Interestingly, compared to baseline, both patients with and without steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, (P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness (≥ 7 kPa). CONCLUSION Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.
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Affiliation(s)
- Mazen Noureddin
- Fatty Liver Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Micaela M Wong
- California Liver Research Institute, Pasadena, CA 91105, United States
| | - Tsuyoshi Todo
- Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Shelly C Lu
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States
| | - Edward A Mena
- California Liver Research Institute, Pasadena, CA 91105, United States
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48
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Liu XQ, Tang RZ. Localized delivery of chemokine for in vitro manipulation of hepatocellular carcinoma cell behaviors during the epithelial–mesenchymal transition. J Biomater Appl 2017; 32:945-956. [DOI: 10.1177/0885328217745774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Xi-Qiu Liu
- Huazhong University of Science and Technology, Tongji Medical College, Wuhan, China
| | - Rui-Zhi Tang
- Institut de Génétique Moléculaire de Montpellier, Montpellier, France
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Xie S, Li Q, Cheng Y, Zhang Y, Zhuo Z, Zhao G, Shen W. Impact of Liver Fibrosis and Fatty Liver on T1rho Measurements: A Prospective Study. Korean J Radiol 2017; 18:898-905. [PMID: 29089822 PMCID: PMC5639155 DOI: 10.3348/kjr.2017.18.6.898] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 04/15/2017] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. MATERIALS AND METHODS This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. RESULTS Liver T1rho and PDFF values were significantly different (p < 0.001), whereas the T2* (p = 0.766) values were similar, among the three groups. Mean liver T1rho values in the fibrotic group (52.6 ± 6.8 ms) were significantly higher than those of healthy subjects (44.9 ± 2.8 ms, p < 0.001) and fatty liver group (45.0 ± 3.5 ms, p < 0.001). Mean liver T1rho values were similar between healthy subjects and fatty liver group (p = 0.999). PDFF values in the fatty liver group (16.07 ± 10.59%) were significantly higher than those of healthy subjects (1.43 ± 1.36%, p < 0.001) and fibrosis group (1.07 ± 1.06%, p < 0.001). PDFF values were similar in healthy subjects and fibrosis group (p = 0.984). Mean T1rho values performed well to detect fibrosis at a threshold of 49.5 ms (area under the ROC curve, 0.855), had a moderate correlation with liver stiffness (r = 0.671, p = 0.012), and no correlation with PDFF, T2* values, subject age, or body mass index (p > 0.05). CONCLUSION T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver.
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Affiliation(s)
- Shuangshuang Xie
- Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, China
| | - Qing Li
- Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, China
| | - Yue Cheng
- Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, China
| | - Yu Zhang
- Clinical Science, Philips Healthcare, Beijing 100600, China
| | - Zhizheng Zhuo
- Clinical Science, Philips Healthcare, Beijing 100600, China
| | - Guiming Zhao
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China
| | - Wen Shen
- Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, China
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50
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Seki K, Shima T, Oya H, Mitsumoto Y, Mizuno M, Okanoue T. Assessment of transient elastography in Japanese patients with non-alcoholic fatty liver disease. Hepatol Res 2017; 47:882-889. [PMID: 27753194 DOI: 10.1111/hepr.12829] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 09/28/2016] [Accepted: 10/16/2016] [Indexed: 12/15/2022]
Abstract
AIM Transient elastography (TE) is a non-invasive method for predicting liver fibrosis. However, there are limited data regarding the performance of TE in Japanese patients with non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association between liver stiffness measurement (LSM) by TE and liver fibrosis stage, and define a cut-off value for predicting liver fibrosis. METHODS A total of 171 Japanese patients with biopsy-proven NAFLD underwent LSM using TE with FibroScan. The area under the receiver operating characteristic curve of LSM and other non-invasive markers of liver fibrosis were compared to determine the most accurate method of predicting liver fibrosis. RESULTS Liver stiffness measurement significantly correlated with fibrosis stage (P < 0.001). The areas under the receiver operating characteristic curve of LSM for fibrosis stage ≥1 and ≥3 was 0.85 and 0.91, respectively and were higher than those of the aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, fibrosis-4 index, and NAFLD fibrosis score. The best cut-off values of LSM fibrosis stage ≥1 and ≥3 were 7.2 kPa (sensitivity 78.5%, specificity 78.3%) and 10.0 kPa (sensitivity 89.5%, specificity 87.6%), respectively. The combination of LSM (≥10 kPa) and type IV collagen 7 s (≥6.0 ng/mL) had a specificity of 97.6% for advanced fibrosis. The LSM in patients with high alanine aminotransferase levels or high body mass index was associated with false positive results regarding advanced fibrosis. CONCLUSIONS In NAFLD patients, TE has excellent utility for the assessment of liver fibrosis, particularly for advanced stage cases. The cut-off value of LSM by TE for predicting liver fibrosis stage ≥3 is 10.0 kPa in Japanese NAFLD patients.
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Affiliation(s)
- Kojiro Seki
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Hirohisa Oya
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Yasuhide Mitsumoto
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Masayuki Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
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