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Bai X, Pu C, Zhen W, Huang Y, Zhang Q, Li Z, Zhang Y, Xu R, Yao Z, Wu W, Sun M, Li X. Identifying liver cirrhosis in patients with chronic hepatitis B: an interpretable machine learning algorithm based on LSM. Ann Med 2025; 57:2477294. [PMID: 40104981 PMCID: PMC11924261 DOI: 10.1080/07853890.2025.2477294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/17/2025] [Accepted: 02/13/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) is a common cause of liver cirrhosis (LC), a condition associated with an unfavourable prognosis. Therefore, timely diagnosis of LC in CHB patients is crucial. OBJECTIVE This study aimed to enhance the diagnostic accuracy of LC in CHB patients by integrating liver stiffness measurement (LSM) with traditional indicators. METHODS The study participants were randomly divided into training and internal validation sets. Employing the least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) for feature selection, we developed both traditional logistic regression and five machine learning models (k-nearest neighbors, random forest (RF), artificial neural network, support vector machine and eXtreme Gradient Boosting). Performance evaluation included receiver operating characteristic curves, calibration curves and decision curve analysis. Shapley additive explanations (SHAP) was employed to improve the interpretability of the optimal model. RESULTS We retrospectively included 1609 patients with CHB, among whom 470 were diagnosed with cirrhosis. Cirrhosis was diagnosed based on histological confirmation or clinical assessment, supported by characteristic findings on abdominal ultrasound and corroborative evidence such as thrombocytopenia, varices or imaging from CT/MRI. In the internal validation, the RF model achieved an accuracy above 0.80 and an AUC above 0.80, with outstanding calibration ability and clinical net benefit. Additionally, the model exhibited excellent predictive performance in an independent external validation set. The SHAP analysis indicated that LSM contributed the most to the model. The model still showed strong discriminative power when using only LSM or traditional indicators alone. CONCLUSIONS Machine learning models, especially the RF model, can effectively identify LC in CHB patients. Integrating LSM with traditional indicators can enhance diagnostic performance.
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Affiliation(s)
- Xueting Bai
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Chunwen Pu
- Dalian Public Health Clinical Center, Dalian, Liaoning province, China
| | - Wenchong Zhen
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Yushuang Huang
- Dalian Public Health Clinical Center, Dalian, Liaoning province, China
| | - Qian Zhang
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Zihan Li
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Yixin Zhang
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Rongxuan Xu
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Zhihan Yao
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Wei Wu
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
| | - Mei Sun
- Dalian Public Health Clinical Center, Dalian, Liaoning province, China
| | - Xiaofeng Li
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian, China
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Oliveira IM, da Silva WPR, Ribeiro RR, Lopes MM, Costa PRDS, Borges NC. Ultrasound elastography in dogs: Physical principles and application in intestinal evaluation. Vet World 2024; 17:2985-2991. [PMID: 39897366 PMCID: PMC11784064 DOI: 10.14202/vetworld.2024.2985-2991] [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: 07/15/2024] [Accepted: 11/12/2024] [Indexed: 02/04/2025] Open
Abstract
Ultrasound elastography provides diagnostic information based on tissue elasticity. There is a lack of specific studies on the application of elastography in canine intestinal assessment. Therefore, we reviewed comparative medicine studies and those referring to the literature listed in the databases. Static and dynamic elastography techniques are widely applied in human intestinal diseases, especially Chron's disease, but few studies have investigated the application of these modalities in canine enteropathies. This case raises questions about the use of new diagnostic imaging techniques in veterinary gastroenterology and highlights the need for further research. Hence, this study aimed to review the literature on the physical principles of elastography and its clinical application in the intestinal evaluation of dogs.
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Affiliation(s)
- Iago Martins Oliveira
- Programa de Pós-graduação em Ciência Animal, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Rodovia Goiânia - Nova Veneza, km 8, Campus Samambaia, 74690-900 Goiânia, Goiás, Brasil
| | - Wanessa Patrícia Rodrigues da Silva
- Programa de Pós-graduação em Ciência Animal, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Rodovia Goiânia - Nova Veneza, km 8, Campus Samambaia, 74690-900 Goiânia, Goiás, Brasil
| | - Rafaela Rodrigues Ribeiro
- Escola de Ciências Médicas e da Vida, Pontifícia Universidade Católica de Goiás, Câmpus II, Av. Engler, s/n - Jardim Mariliza, 74885-460, Goiânia, Goiás, Brasil
| | - Mariana Moreira Lopes
- Escola de Ciências Médicas e da Vida, Pontifícia Universidade Católica de Goiás, Câmpus II, Av. Engler, s/n - Jardim Mariliza, 74885-460, Goiânia, Goiás, Brasil
| | - Paulo Renato dos Santos Costa
- Departamento de Veterinária, Universidade Federal de Viçosa, Avenida PH Rolfs, s/n Campus Universitário, 36570.900, Viçosa, Minas Gerais, Brasil
| | - Naida Cristina Borges
- Departamento de Medicina Veterinária, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Rodovia Goiânia - Nova Veneza, km 8, Campus Samambaia, 74690-900 Goiânia, Goiás, Brasil
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Ahmed N, Kumari A, Murty RS. FibroScan's evolution: a critical 20-year review. J Ultrasound 2024:10.1007/s40477-024-00971-z. [PMID: 39562432 DOI: 10.1007/s40477-024-00971-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 10/11/2024] [Indexed: 11/21/2024] Open
Abstract
FibroScan, initially designed for assessing cheese maturity, has evolved into a crucial medical tool for liver fibrosis diagnosis. This systematic review explores its development history, functionality, and pros and cons compared to traditional liver biopsy. Precision in various clinical settings is scrutinised, emphasising FibroScan's accuracy in conditions like NAFLD and viral-induced liver disease. The article also delves into its potential in paediatrics, its relevance in monitoring COVID-19-related liver complications, and its role in predicting hepatocellular carcinoma risk, Technical aspects, including transducers, imaging integration, and portability, are examined. Various methods for evaluating liver fibrosis are discussed, highlighting FibroScan's suitability for advanced stages, contrasting with the gold standard of liver biopsy for early stages. The impact of FibroScan on long-term liver conditions is emphasised, focusing on early detection, progression monitoring, reduced invasive biopsies, and hepatocellular carcinoma risk prediction. This systematic review underscores FibroScan's transformative potential in liver disease treatment and predicts ongoing research to enhance early detection, disease monitoring, and explore new clinical applications. Anticipated advances include FibroScan-guided liver biopsy, artificial intelligence data analysis, and point-of-care device development, promising a further revolution in liver disease management. The article concludes with optimistic prospects for FibroScan's future.
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Affiliation(s)
- Nisar Ahmed
- Aditya Pharmacy Collage, Surampalem, Andhra Pradesh, India.
- Jawaharlal Nehru Technological University, Kakinada, India.
| | - Ayushi Kumari
- Aditya Pharmacy Collage, Surampalem, Andhra Pradesh, India
- Jawaharlal Nehru Technological University, Kakinada, India
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Terracciani F, Falcomatà A, Gallo P, Picardi A, Vespasiani-Gentilucci U. Prognostication in NAFLD: physiological bases, clinical indicators, and newer biomarkers. J Physiol Biochem 2023; 79:851-868. [PMID: 36472795 DOI: 10.1007/s13105-022-00934-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 11/23/2022] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic in Western countries. Notably, while the majority of NAFLD patients will not evolve until advanced liver disease, a minority of them will progress towards liver-related events. Therefore, risk stratification and prognostication are emerging as fundamental in order to optimize human and economic resources for the care of these patients.Liver fibrosis has been clearly recognized as the main predictor of poor hepatic and extrahepatic outcomes. However, a prediction based only on the stage of fibrosis is near-sighted and static, as it does not capture the propensity of disease to further progress, the speed of progression and their changes over time. These determinants, which result from the interaction between genetic predisposition and acquired risk factors (obesity, diabetes, etc.), express themselves in disease activity, and can be synthesized by biomarkers of hepatic inflammation and fibrogenesis.In this review, we present the currently available clinical tools for risk stratification and prognostication in NAFLD specifically with respect to the risk of progression towards hard hepatic outcomes, i.e., liver-related events and death. We also discuss about the genetic and acquired drivers of disease progression, together with the physiopathological bases of their come into action. Finally, we introduce the most promising biomarkers in the direction of repeatedly assessing disease activity over time, mainly in response to future therapeutic interventions.
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Affiliation(s)
- Francesca Terracciani
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Andrea Falcomatà
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Paolo Gallo
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy.
| | - Antonio Picardi
- Hepatology and Clinical Medicine Unit, University Campus Bio-Medico of Rome, Rome, Italy
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Palmieri R, Paterno G, Mallegni F, Frenza F, De Bernardis I, Moretti F, Meddi E, Del Principe MI, Maurillo L, Venditti A, Buccisano F. Therapy-related Myeloid Neoplasms: Considerations for Patients' Clinical Evaluation. Mediterr J Hematol Infect Dis 2023; 15:e2023051. [PMID: 37705524 PMCID: PMC10497317 DOI: 10.4084/mjhid.2023.051] [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: 07/18/2023] [Accepted: 08/11/2023] [Indexed: 09/15/2023] Open
Abstract
Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio.
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Affiliation(s)
- Raffaele Palmieri
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle (WA), USA
| | | | - Flavia Mallegni
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Federica Frenza
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Ilenia De Bernardis
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Federico Moretti
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Elisa Meddi
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | | | - Luca Maurillo
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Adriano Venditti
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Francesco Buccisano
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
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Komiyama Y, Motosugi U, Maekawa S, Osawa L, Nakakuki N, Takada H, Muraoka M, Suzuki Y, Sato M, Takano S, Fukasawa M, Yamaguchi T, Onishi H, Yin M, Enomoto N. Early diagnosis of hepatic inflammation in Japanese nonalcoholic fatty liver disease patients using 3D MR elastography. Hepatol Res 2023; 53:208-218. [PMID: 36372908 PMCID: PMC10600503 DOI: 10.1111/hepr.13858] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 11/07/2022] [Accepted: 11/10/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND The damping ratio (DR) and the loss modulus (G″) obtained by 3D MR elastography complex modulus analysis has been reported recently to reflect early intrahepatic inflammation, and is expected to be a noninvasive biomarker of inflammation in nonalcoholic fatty liver disease (NAFLD). However, the role of the DR and the G″ in Japanese NAFLD patients remains unclear. METHODS We enrolled 39 Japanese patients with NAFLD who underwent liver biopsy and 3D MR elastography within 1 month and analyzed the association between DR, G″, and histological activity. RESULTS Regarding DR, no evident correlation was observed between the DR and histological activity (p = 0.14) when patients with all fibrosis stages were included. However, when patients were restricted up to stage F2 fibrosis, the association of the DR and inflammation became significant, the DR increasing with the degree of activity (p = 0.02). Among the constituents of fibrosis activity, ballooning correlated with the DR (p < 0.01) while lobular inflammation did not. Regarding G″, it was correlated with histological activity (p < 0.01), ballooning (p < 0.01), and lobular inflammation (p < 0.01) in patients with all fibrosis stages and in patients up to F2 fibrosis (p = 0.03 for activity and p = 0.04 for ballooning). The best cutoff value of DR for hepatitis activity in patients within the F2 stage was 0.094 (area under the receiver operating characteristic curve 0.775, 95% CI: 0.529-1.000) and G″ was 0.402 (area under the receiver operating characteristic curve 0.825, 95% CI: 0.628-1.000). CONCLUSIONS The DR and G″ reflected the histological activity in Japanese patients with NAFLD during the early stage, indicating these values for noninvasive diagnosis of inflammation in Japanese patients with NAFLD.
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Affiliation(s)
- Yasuyuki Komiyama
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Utaroh Motosugi
- Department or Radiology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Shinya Maekawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Leona Osawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Natsuko Nakakuki
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Hitomi Takada
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Masaru Muraoka
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Yuichiro Suzuki
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Mitsuaki Sato
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Shinichi Takano
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Mitsuharu Fukasawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Tatsuya Yamaguchi
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Hiroshi Onishi
- Department or Radiology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Meng Yin
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
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Sundaram S, Darak H, Kumar S, Giri S, Bhatia S. DAPS score - a novel score for prediction of significant fibrosis in incidentally detected asymptomatic hepatitis B subjects. Clin Exp Hepatol 2023; 9:9-13. [PMID: 37064839 PMCID: PMC10090992 DOI: 10.5114/ceh.2023.124518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/12/2022] [Indexed: 04/18/2023] Open
Abstract
AIM OF THE STUDY Significant fibrosis is an indication for treatment in hepatitis B patients with normal transaminase levels. The present study was aimed at analyzing the factors associated with significant fibrosis in incidentally detected asymptomatic hepatitis B subjects (IDAHS) and developing a model for fibrosis prediction for use in low-resource settings. MATERIAL AND METHODS This is a single-center retrospective analysis of data on IDAHS who had undergone FibroScan. The variables associated with significant fibrosis in the derivation cohort were subjected to multivariate analysis by logistic regression. The model was applied to the validation cohort for fibrosis prediction. RESULTS A total of 299 patients (mean age: 42.6 years, males: 63.2%) were included in the model derivation. Significant fibrosis was found in 27.4% (82/299) of the patients and 16.8% (30/178) of those with normal transaminase. On multivariate analysis, age, lower platelet count, and presence of diabetes were associated with fibrosis. Serum glutamic pyruvic transaminase (SGPT) was included in the model as it was nearing towards in multivariate analysis. The DAPS (diabetes, age, platelet count, SGPT) score was proposed with equal weightage to each variable. Based on the cumulative score, patients were categorized as having low risk (DAPS score 0-2) or high risk (DAPS score 3-4). The specificity of the model in derivation and validation cohorts was 98.2% and 97.6%, respectively, while the accuracy was 83.6% and 80%, respectively. CONCLUSIONS Approximately 17% of IDAHS with normal transaminase have significant fibrosis. The DAPS score can be used easily as a bedside tool for assessment of significant fibrosis in IDAHS with excellent specificity.
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Iwanaga S, Matsuse H, Hashida R, Bekki M, Kawaguchi T, Shiba N. The Effect of Walking Combined with Neuromuscular Electrical Stimulation on Liver Stiffness and Insulin Resistance in Patients with Non-alcoholic Fatty Liver Disease: An Exploratory Randomized Controlled Trial. Kurume Med J 2023; 67:137-146. [PMID: 36450482 DOI: 10.2739/kurumemedj.ms674001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Increased liver stiffness and insulin resistance are important therapeutic targets in patients with nonalcoholic fatty liver disease (NAFLD). A hybrid training system (HTS) has been developed which combines application of electrical stimulation and volitional contractions. We compared the effect of walking exercise (5.6 km/h) both with and without simultaneous HTS on liver stiffness and insulin resistance. In a single-blind, controlled trial, 32 subjects with NAFLD were randomized to 12 weeks of triweekly 30 minute walking exercise with either HTS (HTS group) or without HTS (control group). Transient elastography for the assessment of liver stiffness, body weight, visceral fat, the homeostasis model assessment of insulin resistance, fasting blood glucose, serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase were evaluated. Data were evaluated using the linear model after adjusting the baseline value. In the subjects with BMI of 27 kg/m2 or more, the decrement of transient elastography in the HTS group was significantly larger than in the control group (mean ± standard error: Δ2.13 ± 0.64 kPa vs. Δ-0.67 ± 0.42 kPa, p=0.0009). There were no significant differences between groups in other endpoints. These results showed that simultaneously combining electrical stimulation with walking exercise could potentially improve liver stiffness in people who have NAFLD. In fact, because the exercise effect was increased by HTS without increasing the walking speed, this HTS could be especially useful for obese or overweight subjects, in whom NAFLD and joint problems often coexist. However, its effects on insulin resistance and body composition were not clear.
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Affiliation(s)
- Sohei Iwanaga
- Division of Rehabilitation, Kurume University Hospital
| | - Hiroo Matsuse
- Division of Rehabilitation, Kurume University Hospital
| | - Ryuki Hashida
- Division of Rehabilitation, Kurume University Hospital
| | | | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Naoto Shiba
- Division of Rehabilitation, Kurume University Hospital
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Jiang M, Zhang X, Wu X, Xu Z, Pan J, He H, Luo Y, Chen J. The diagnostic value of novel ultrasound attenuation analysis in detecting liver steatosis identified by the controlled attenuation parameter: a diagnostic accuracy study. ANNALS OF TRANSLATIONAL MEDICINE 2023; 11:38. [PMID: 36819532 PMCID: PMC9929820 DOI: 10.21037/atm-22-5821] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 12/29/2022] [Indexed: 01/12/2023]
Abstract
Background Ultrasound attenuation analysis (USAT) is a type of novel ultrasound attenuation imaging that can be used to detect hepatic steatosis based on the attenuation coefficient. We sought to evaluate the diagnostic accuracy for assessing the severity of liver steatosis by USAT using the controlled attenuation parameter (CAP) as a reference in patients with non-alcoholic fatty liver diseases (NAFLD) and chronic hepatitis B (CHB) infections. Methods In total, 326 consecutive subjects with or without chronic liver diseases were enrolled in this study who underwent CAP examination and USAT to evaluate hepatic steatosis from October 2022 to November 2022 at The Fourth Affiliated Hospital of Zhejiang University School of Medicine. Hepatic steatosis stage (S) was determined by CAP according to the following cut-off values recommended by the manufacturer: S ≥ S1 (≥11%, mild): 238 dB/m; S ≥ S2 (≥34%, moderate): 259 dB/m; and S ≥ S3 (≥67%, severe): 292 dB/m, and thus the optimal cut-off values for the USAT were acquired. The area under the receiver operating characteristic curves (AUROCs) for the categories of steatosis were used to measure the diagnostic accuracy of USAT. Results A total of 296 patients were recruited, including 101 (34.1%) patients with NAFLD, 172 (58.1%) with CHB and the remainder were healthy control subjects (7.8%). We used the CAP as the reference standard and found that the USAT increased gradually as the stage of steatosis increased (P<0.001). A strong positive correlation was found between USAT and CAP (r=0.787, P<0.001). In the whole population, the AUROCs of the USAT for S ≥ S1, S ≥ S2 and S ≥ 3 were 0.89, 0.90, and 0.90, respectively, and the cut-off values according to the Youden index for S ≥ S1, S ≥ S2, and S ≥ 3 were 0.62, 0.66, and 0.72 dB/cm/MHz, respectively. Our study showed that the USAT had a good ability to detect hepatic steatosis in NAFLD and CHB patients. Conclusions USAT had a strong association with CAP and a good diagnostic capability in the detection of hepatic steatosis, which appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis.
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Affiliation(s)
- Meijuan Jiang
- Department of Ultrasound Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China
| | - Xuanxuan Zhang
- Department of Ultrasound Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China
| | - Xiaojin Wu
- Zhejiang University School of Medicine, Hangzhou, China
| | - Zhikang Xu
- Zhejiang University School of Medicine, Hangzhou, China
| | - Jianlian Pan
- Department of Clinical and Research, Shenzhen Mindray Bio-medical Electronics Co., Ltd., Shenzhen, China
| | - Huiling He
- Department of Ultrasound Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China
| | - Yunkai Luo
- Department of Ultrasound Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China
| | - Jian Chen
- Department of Ultrasound Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, China
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Clinical and Molecular Biomarkers for Diagnosis and Staging of NAFLD. Int J Mol Sci 2021; 22:ijms222111905. [PMID: 34769333 PMCID: PMC8585051 DOI: 10.3390/ijms222111905] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 10/30/2021] [Accepted: 10/30/2021] [Indexed: 12/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic pathology in industrialized countries, affecting about 25% of the general population. NAFLD is a benign condition, however, it could evolve toward more serious diseases, including non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard for NAFLD diagnosis. Due to the risks associated with liver biopsy and the impossibility to apply it on a large scale, it is now necessary to identify non-invasive biomarkers, which may reliably identify patients at higher risk of progression. Therefore, several lines of research have tried to address this issue by identifying novel biomarkers using omics approaches, including lipidomics, metabolomics and RNA molecules' profiling. Thus, in this review, we firstly report the conventional biomarkers used in clinical practice for NAFL and NASH diagnosis as well as fibrosis staging, and secondly, we pay attention to novel biomarkers discovered through omics approaches with a particular focus on RNA biomarkers (microRNAs, long-noncoding RNAs), showing promising diagnostic performance for NAFL/NASH diagnosis and fibrosis staging.
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Breath-Taking Perspectives and Preliminary Data toward Early Detection of Chronic Liver Diseases. Biomedicines 2021; 9:biomedicines9111563. [PMID: 34829792 PMCID: PMC8615034 DOI: 10.3390/biomedicines9111563] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/20/2021] [Accepted: 10/22/2021] [Indexed: 12/17/2022] Open
Abstract
The gold standard method for chronic liver diseases diagnosis and staging remains liver biopsy, despite the spread of less invasive surrogate modalities based on imaging and blood biomarkers. Still, more than 50% of chronic liver disease cases are detected at later stages when patients exhibit episodes of liver decompensation. Breath analysis represents an attractive means for the development of non-invasive tests for several pathologies, including chronic liver diseases. In this perspective review, we summarize the main findings of studies that compared the breath of patients with chronic liver diseases against that of control subjects and found candidate biomarkers for a potential breath test. Interestingly, identified compounds with best classification performance are of exogenous origin and used as flavoring agents in food. Therefore, random dietary exposure of the general population to these compounds prevents the establishment of threshold levels for the identification of disease subjects. To overcome this limitation, we propose the exogenous volatile organic compounds (EVOCs) probe approach, where one or multiple of these flavoring agent(s) are administered at a standard dose and liver dysfunction associated with chronic liver diseases is evaluated as a washout of ingested compound(s). We report preliminary results in healthy subjects in support of the potential of the EVOC Probe approach.
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Shanmuganathan M, Sarfaraz MO, Kroezen Z, Philbrick H, Poon R, Don-Wauchope A, Puglia M, Wishart D, Britz-McKibbin P. A Cross-Platform Metabolomics Comparison Identifies Serum Metabolite Signatures of Liver Fibrosis Progression in Chronic Hepatitis C Patients. Front Mol Biosci 2021; 8:676349. [PMID: 34414211 PMCID: PMC8370474 DOI: 10.3389/fmolb.2021.676349] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 07/19/2021] [Indexed: 12/15/2022] Open
Abstract
Metabolomics offers new insights into disease mechanisms that is enhanced when adopting orthogonal instrumental platforms to expand metabolome coverage, while also reducing false discoveries by independent replication. Herein, we report the first inter-method comparison when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) and nuclear magnetic resonance (NMR) spectroscopy for characterizing the serum metabolome of patients with liver fibrosis in chronic hepatitis C virus (HCV) infection (n = 20) and non-HCV controls (n = 14). In this study, 60 and 30 serum metabolites were detected frequently (>75%) with good technical precision (median CV < 10%) from serum filtrate samples (n = 34) when using standardized protocols for MSI-CE-MS and NMR, respectively. Also, 20 serum metabolite concentrations were consistently measured by both methods over a 500-fold concentration range with an overall mean bias of 9.5% (n = 660). Multivariate and univariate statistical analyses independently confirmed that serum choline and histidine were consistently elevated (p < 0.05) in HCV patients with late-stage (F2-F4) as compared to early-stage (F0-F1) liver fibrosis. Overall, the ratio of serum choline to uric acid provided optimal differentiation of liver disease severity (AUC = 0.848, p = 0.00766) using a receiver operating characteristic curve, which was positively correlated with liver stiffness measurements by ultrasound imaging (r = 0.606, p = 0.0047). Moreover, serum 5-oxo-proline concentrations were higher in HCV patients as compared to non-HCV controls (F = 4.29, p = 0.0240) after adjustment for covariates (age, sex, BMI), indicative of elevated oxidative stress from glutathione depletion with the onset and progression of liver fibrosis. Both instrumental techniques enable rapid yet reliable quantification of serum metabolites in large-scale metabolomic studies with good overlap for biomarker replication. Advantages of MSI-CE-MS include greater metabolome coverage, lower operating costs, and smaller sample volume requirements, whereas NMR offers a robust platform supported by automated spectral and data processing software.
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Affiliation(s)
- Meera Shanmuganathan
- Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada
| | | | - Zachary Kroezen
- Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada
| | - Holly Philbrick
- Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada
| | - Richel Poon
- Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada
| | - Andrew Don-Wauchope
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Marco Puglia
- Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, ON, Canada
| | - David Wishart
- Departments of Biological Sciences and Computing Science, University of Alberta, Edmonton, AB, Canada
| | - Philip Britz-McKibbin
- Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada
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13
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Papachristodoulou A, Kavvadas D, Karamitsos A, Papamitsou T, Chatzidimitriou M, Sioga A. Diagnosis and Staging of Pediatric Non-Alcoholic Fatty Liver Disease: Is Classical Ultrasound the Answer? Pediatr Rep 2021; 13:312-321. [PMID: 34201230 PMCID: PMC8293345 DOI: 10.3390/pediatric13020039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/19/2021] [Accepted: 06/01/2021] [Indexed: 12/15/2022] Open
Abstract
The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.
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Affiliation(s)
- Angeliki Papachristodoulou
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
| | - Dimitrios Kavvadas
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
| | - Athanasios Karamitsos
- 2nd Department of Ophthalmology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece;
| | - Theodora Papamitsou
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
| | - Maria Chatzidimitriou
- Department of Biomedical Sciences, School of Health Sciences, International University of Greece, 574 00 Thessaloniki, Greece;
| | - Antonia Sioga
- Laboratory of Histology and Embryology, School of Medicine, Faculty of Health, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; (A.P.); (D.K.); (A.S.)
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14
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Bouazizi K, Zarai M, Marquet F, Aron-Wisnewsky J, Clément K, Redheuil A, Kachenoura N. Adipose tissue fibrosis assessed by high resolution ex vivo MRI as a hallmark of tissue alteration in morbid obesity. Quant Imaging Med Surg 2021; 11:2162-2168. [PMID: 33936996 DOI: 10.21037/qims-20-879] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
To determine whether magnetic resonance imaging (MRI) when used in an optimal ex vivo setting can help detecting and quantifying the 3D fibrosis fraction in human subcutaneous adipose tissue (SAT) samples, as compared to histology. This prospective observational study was approved by our institutional review board 3D MRI acquisitions were performed at 4.0 T (Bruker) on XX human SAT samples (around 1 cm3) collected from biopsy in morbidly obese patients. Such acquisitions included saturation-recovery T1 mapping (spatial resolution: 200 µm, acquisition time: ~16 minutes) and DIXON imaging (spatial resolution: 200 µm, acquisition time: ~20 minutes). After MRI, histological quantification of fibrosis was performed using picrosirius staining. T1 maps were clustered based on a k-means algorithm allowing quantification of fibrosis within the adipose tissue and percentage of fibrosis over the entire sample volume was calculated. Fat maps were computed from DIXON in-phase and out-of-phase images. The 3D MRI fibrosis percentage within the SAT samples were comprised between 6% and 15%. Excellent correlations and levels of agreement were observed between single slice MRI and histology (r=0.9, P=0.08) and between 3D MRI and histology in terms fibrosis percentages within SAT samples (r=0.9, P=0.01). High Field ex vivo MRI was able to quantify fibrosis in human SAT samples with high agreement with histology and moreover to provide 3D SAT fibrosis quantification avoiding histological sampling errors.
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Affiliation(s)
- Khaoula Bouazizi
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Sorbonne Université, Laboratoire d'Imagerie Biomédicale (LIB), Paris, France
| | - Mohamed Zarai
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Florian Marquet
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Sorbonne Université, INSERM, Nutrition and Obesities; approches systémiques (NutriOmique), Pitié-Salpêtrière Hospital, Nutrition department, Paris, France
| | - Judith Aron-Wisnewsky
- Sorbonne Université, INSERM, Nutrition and Obesities; approches systémiques (NutriOmique), Pitié-Salpêtrière Hospital, Nutrition department, Paris, France.,Assistance Publique Hôpitaux de Paris, Nutrition department, CRNH Ile-de-France, Pitié-Salpêtrière Hospital, Paris, France
| | - Karine Clément
- Sorbonne Université, INSERM, Nutrition and Obesities; approches systémiques (NutriOmique), Pitié-Salpêtrière Hospital, Nutrition department, Paris, France.,Assistance Publique Hôpitaux de Paris, Nutrition department, CRNH Ile-de-France, Pitié-Salpêtrière Hospital, Paris, France
| | - Alban Redheuil
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Sorbonne Université, Laboratoire d'Imagerie Biomédicale (LIB), Paris, France.,Unité d'Imagerie Cardiovasculaire et Thoracique (ICT), Pitié-Salpêtrière Hospital, Paris, France
| | - Nadjia Kachenoura
- Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.,Sorbonne Université, Laboratoire d'Imagerie Biomédicale (LIB), Paris, France
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15
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DiClemente RJ, Brown JL, Capasso A, Revzina N, Sales JM, Boeva E, Gutova LV, Khalezova NB, Belyakov N, Rassokhin V. Computer-based alcohol reduction intervention for alcohol-using HIV/HCV co-infected Russian women in clinical care: study protocol for a randomized controlled trial. Trials 2021; 22:147. [PMID: 33596972 PMCID: PMC7887790 DOI: 10.1186/s13063-021-05079-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 01/29/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Russia has a high prevalence of human immunodeficiency virus (HIV) infections. In 2018, over one million persons were living with HIV (PLWH); over a third were women. A high proportion of HIV-infected women are co-infected with hepatitis C virus (HCV), and many consume alcohol, which adversely affects HIV and HCV treatment and prognosis. Despite the triple epidemics of alcohol use, HIV and HCV, and the need for interventions to reduce alcohol use among HIV/HCV co-infected women, evidence-based alcohol reduction interventions for this vulnerable population are limited. To address this gap, we developed a clinical trial to evaluate the efficacy of a computer-based intervention to reduce alcohol consumption among HIV/HCV co-infected women in clinical care. METHODS In this two-arm parallel randomized controlled trial, we propose to evaluate the efficacy of a culturally adapted alcohol reduction intervention delivered via a computer for HIV/HCV co-infected Russian women. The study population consists of women 21-45 years old with confirmed HIV/HCV co-infection who currently use alcohol. Intervention efficacy is assessed by a novel alcohol biomarker, ethyl glucuronide (EtG), and biomarkers of HIV and HCV disease progression. Women are randomized to trial conditions in a 1:1 allocation ratio, using a computer-generated algorithm to develop the assignment sequence and concealment of allocation techniques to minimize assignment bias. Women are randomized to either (1) the computer-based alcohol reduction intervention or (2) the standard-of-care control condition. We will use an intent-to-treat analysis and logistic and linear generalized estimating equations to evaluate intervention efficacy, relative to the standard of care, in enhancing the proportion of women with a laboratory-confirmed negative EtG at each research study visit over the 9-month follow-up period. Additional analyses will evaluate intervention effects on HIV (viral load and CD4+ levels) and HCV markers of disease progression (FibroScan). DISCUSSION The proposed trial design and analysis provides an appropriate conceptual and methodological framework to assess the efficacy of the computer-based intervention. We propose to recruit 200 participants. The intervention, if efficacious, may be an efficient and cost-effective alcohol reduction strategy that is scalable and can be readily disseminated and integrated into clinical care in Russia to reduce women's alcohol consumption and enhance HIV/HCV prognosis. TRIAL REGISTRATION ClinicalTrials.gov NCT03362476 . Registered on 5 December 2017.
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Affiliation(s)
| | - Jennifer L Brown
- Department of Psychology, University of Cincinnati, Cincinnati, OH, USA
- Addiction Sciences Division, Department of Psychiatry & Behavioural Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Center for Addiction Research, University of Cincinnati, Cincinnati, OH, USA
| | - Ariadna Capasso
- School of Global Public Health, New York University, New York, NY, USA
| | - Natalia Revzina
- Clinical Trials Compliance, Office for Clinical Research, School of Medicine, Emory University, Atlanta, GA, USA
| | - Jessica M Sales
- Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Ekaterina Boeva
- First Saint Petersburg State Pavlov Medical University, Saint Petersburg, Russia
- Saint Petersburg Pasteur Institute, Saint Petersburg, Russia
| | - Lyudmila V Gutova
- First Saint Petersburg State Pavlov Medical University, Saint Petersburg, Russia
| | - Nadia B Khalezova
- First Saint Petersburg State Pavlov Medical University, Saint Petersburg, Russia
| | - Nikolay Belyakov
- First Saint Petersburg State Pavlov Medical University, Saint Petersburg, Russia
- Saint Petersburg Pasteur Institute, Saint Petersburg, Russia
| | - Vadim Rassokhin
- First Saint Petersburg State Pavlov Medical University, Saint Petersburg, Russia
- Saint Petersburg Pasteur Institute, Saint Petersburg, Russia
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16
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Ren X, Xia S, Zhang L, Li R, Zhou W, Ji R, Zhou J, Tian J, Zhan W. Analysis of liver steatosis analysis and controlled attenuation parameter for grading liver steatosis in patients with chronic hepatitis B. Quant Imaging Med Surg 2021; 11:571-578. [PMID: 33532257 DOI: 10.21037/qims-19-1091] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Background Chronic hepatitis B is the most common chronic liver disease in China. For patients with chronic hepatitis B, steatosis increases the risk of cirrhosis and hepatocellular carcinoma. This study aimed to analyze and compare the clinical value of a newly developed ultrasound attenuation parameter, liver steatosis analysis (LiSA), acquired by Hepatus (Mindray, China), and controlled attenuation parameter (CAP), a widely used ultrasound attenuation parameter acquired by FibroScan (Echosens, France), for grading liver steatosis in patients with chronic hepatitis B infection. Methods A total of 203 patients were divided into two groups according to liver fat content validated by liver biopsy: group 1 (liver fat content <10%) and group 2 (liver fat content ≥10%). All patients underwent LiSA and CAP examinations. Receiver operating characteristic (ROC) curves were calculated for the two ultrasound attenuation tools. Results Both LiSA and CAP successfully discriminated between patients in group 1 and group 2. ROC curves showed that both tools had good diagnostic ability (AUC: >0.7) for steatosis ≥10%, and the performance of LiSA was significantly better than CAP (AUC: 0.859 vs. 0.801, P=0.048). Using optimal cut-off points, LiSA had specificity and sensitivity of 96.23% and 76.08%, respectively, for the diagnosis of steatosis ≥10%, compared to 91.53% and 72.10%, respectively, for CAP. Conclusions LiSA and CAP are extremely efficient tools for assessing liver steatosis, even at a low grade. Both parameters are non-invasive, inexpensive, and easy to use, and can provide immediate results with high sensitivity.
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Affiliation(s)
- Xinping Ren
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.,Department of Ultrasound, Wuxi Branch of Ruijin Hospital, Wuxi, China
| | - Shujun Xia
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Lu Zhang
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ruokun Li
- Institute of Endocrinology, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Wei Zhou
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ri Ji
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jianqiao Zhou
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jingyan Tian
- Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Weiwei Zhan
- Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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17
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T1ρ magnetic resonance imaging value as a potential marker to assess the severity of liver fibrosis: A pilot study. Eur J Radiol Open 2021; 8:100321. [PMID: 33490312 PMCID: PMC7806785 DOI: 10.1016/j.ejro.2021.100321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/24/2020] [Accepted: 12/30/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose Assessment of liver fibrosis is essential for the management of liver disease. Although liver biopsy is the gold-standard modality for the diagnosis of liver fibrosis, it has some limitations. Thus, other methods are required to overcome the disadvantages of a liver biopsy. T1ρ magnetic resonance imaging (MRI) values are potential biomarkers for liver cirrhosis. This study aimed to assess the relationship between T1ρ MRI values and liver fibrosis severity by measuring the correlation between T1ρ values and shear wave elastography (SWE) values, which are routinely used for the diagnosis of liver fibrosis. Methods T1ρ imaging and SWE values were obtained from four healthy volunteers and 16 patients with chronic liver disease. The regions of interest on MR images were drawn and matched with those of the right liver lobe on SWE images. Results The mean T1ρ values of the right liver lobe correlated positively with the mean SWE values (Pearson’s correlation coefficient: 0.783; p < 0.0001; 95 % confidence interval: 0.623–0.880). Conclusion The mean T1ρ values of the right liver lobe may be correlated with the severity of liver fibrosis.
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18
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Heyens LJM, Busschots D, Koek GH, Robaeys G, Francque S. Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment. Front Med (Lausanne) 2021; 8:615978. [PMID: 33937277 PMCID: PMC8079659 DOI: 10.3389/fmed.2021.615978] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 03/22/2021] [Indexed: 12/12/2022] Open
Abstract
An increasing percentage of people have or are at risk to develop non-alcoholic fatty liver disease (NAFLD) worldwide. NAFLD comprises different stadia going from isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is a chronic state of liver inflammation that leads to the transformation of hepatic stellate cells to myofibroblasts. These cells produce extra-cellular matrix that results in liver fibrosis. In a normal situation, fibrogenesis is a wound healing process that preserves tissue integrity. However, sustained and progressive fibrosis can become pathogenic. This process takes many years and is often asymptomatic. Therefore, patients usually present themselves with end-stage liver disease e.g., liver cirrhosis, decompensated liver disease or even hepatocellular carcinoma. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Currently, only a minority of patients with liver fibrosis are identified to be at risk and hence referred for treatment. This is not only because the disease is largely asymptomatic, but also due to the fact that currently liver biopsy is still the golden standard for accurate detection of liver fibrosis. However, performing a liver biopsy harbors some risks and requires resources and expertise, hence is not applicable in every clinical setting and is unsuitable for screening. Consequently, different non-invasive diagnostic tools, mainly based on analysis of blood or other specimens or based on imaging have been developed or are in development. In this review, we will first give an overview of the pathogenic mechanisms of the evolution from isolated steatosis to fibrosis. This serves as the basis for the subsequent discussion of the current and future diagnostic biomarkers and anti-fibrotic drugs.
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Affiliation(s)
- Leen J. M. Heyens
- Faculty of Health and Life Sciences, Hasselt University, Hasselt, Belgium
- School of Nutrition and Translational Research in Metabolism, NUTRIM, Maastricht University, Maastricht, Netherlands
- Department of Gastro-Enterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Dana Busschots
- Faculty of Health and Life Sciences, Hasselt University, Hasselt, Belgium
- School of Nutrition and Translational Research in Metabolism, NUTRIM, Maastricht University, Maastricht, Netherlands
| | - Ger H. Koek
- School of Nutrition and Translational Research in Metabolism, NUTRIM, Maastricht University, Maastricht, Netherlands
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Geert Robaeys
- Faculty of Health and Life Sciences, Hasselt University, Hasselt, Belgium
- Department of Gastro-Enterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium
- Department of Gastroenterology and Hepatology, University Hospital Katholieke Universiteit (KU) Leuven, Leuven, Belgium
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- *Correspondence: Sven Francque
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19
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The Use of Two-Dimensional Shear Wave Elastography in People with Obesity for the Assessment of Liver Fibrosis in Non-Alcoholic Fatty Liver Disease. J Clin Med 2020; 10:jcm10010095. [PMID: 33383965 PMCID: PMC7795317 DOI: 10.3390/jcm10010095] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/15/2020] [Accepted: 12/24/2020] [Indexed: 12/16/2022] Open
Abstract
Obesity is associated with significant comorbidities, including non-alcoholic fatty liver disease (NAFLD). Given its potential to progress to advanced liver disease, monitoring the extent and progress of liver fibrosis and assessing its fibrosis stage are essential. Although liver biopsy is considered to be the gold standard for liver fibrosis staging, it is an invasive procedure with risk of complications. Considering the rising prevalence of obesity and NAFLD globally, developing non-invasive diagnostic methods is a priority. Transient elastography (TE) is increasingly being used to assess the severity of liver disease. However, in the presence of severe obesity, the increased thickness of subcutaneous adipose tissue and changes in anatomy may affect its diagnostic accuracy. Two-dimensional shear wave elastography (2D-SWE) assesses the liver stiffness in real time along with simultaneous anatomic B-mode ultrasound imaging and allows selection of the region of interest. This would suggest that 2D-SWE has several advantages over TE in patients with severe obesity. The purpose of this review is to examine the current literature addressing the use of 2D-SWE in the assessment of liver fibrosis in patients with NAFLD. This review also examines the evidence on the use of 2D-SWE in patients with obesity and NAFLD and compares it to TE as a novel and non-invasive method of assessing liver fibrosis.
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20
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Blesl A, Jüngst C, Lammert F, Fauler G, Rainer F, Leber B, Feldbacher N, Stromberger S, Wildburger R, Spindelböck W, Fickert P, Horvath A, Stadlbauer V. Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut-Liver Axis: A Case Control Study. Nutrients 2020; 12:E2728. [PMID: 32906634 PMCID: PMC7551864 DOI: 10.3390/nu12092728] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 09/02/2020] [Accepted: 09/03/2020] [Indexed: 12/12/2022] Open
Abstract
Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut-liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut-liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment.
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Affiliation(s)
- Andreas Blesl
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Christoph Jüngst
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Zürich, 8032 Zürich, Switzerland;
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany;
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany;
| | - Günter Fauler
- Institute for Medical and Chemical Laboratory Diagnosis, Medical University of Graz, 8036 Graz, Austria;
| | - Florian Rainer
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Bettina Leber
- Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, 8036 Graz, Austria;
| | - Nicole Feldbacher
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Silvia Stromberger
- AUVA Rehabilitation Clinic Tobelbad, 8144 Tobelbad, Austria; (S.S.); (R.W.)
| | - Renate Wildburger
- AUVA Rehabilitation Clinic Tobelbad, 8144 Tobelbad, Austria; (S.S.); (R.W.)
| | - Walter Spindelböck
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Peter Fickert
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Angela Horvath
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
| | - Vanessa Stadlbauer
- Division for Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; (F.R.); (N.F.); (W.S.); (P.F.); (A.H.); (V.S.)
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Mikolasevic I, Lukic A, Juric T, Klapan M, Madzar P, Krolo N, Kolovrat D, Jurica I, Kedmenec I, Kihas D, Ilovaca D, Erstic I, Haralovic V, Cavlina D, Dejhalla E, Erdeljac D, Vukalovic B, Skenderevic N, Milic S. Non-alcoholic fatty liver disease and transient elastography. EXPLORATION OF MEDICINE 2020; 1:205-217. [DOI: 10.37349/emed.2020.00014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 06/15/2020] [Indexed: 01/03/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious condition that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is associated with metabolic syndrome (MetS) and all of its components. According to data, around 25-30% of population has NAFLD. Giving the growing incidence of MetS, obesity and diabetes mellitus type 2, NAFLD related terminal-stage liver disease is becoming prevailing indication for liver transplantation. In order to prevent terminal stage of this disease, it is crucial to determine those that are in risk group, to modify their risk factors and monitor their potential progression. In the absence of other causes of chronic liver disease, the prime diagnosis of NAFLD in daily clinical practice includes anamnesis, laboratory results (increased levels of aminotransferases and gammaglutamil transferases) and imaging methods. The biggest challenge with NAFLD patients is to differentiate simple steatosis from nonalcoholic steatohepatitis, and detection of fibrosis, that is the main driver in NAFLD progression. The gold standard for NAFLD diagnosis still remains the liver biopsy (LB). However, in recent years many noninvasive methods were invented, such as transient elastography (TE). TE (FibroScan®, Echosens, Paris, France) is used for diagnosis of pathological differences of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Investigations in the last years have confirmed that elastographic parameters of steatsis (CAP) and fibrosis (LSM) are reliable biomarkers to non-invasively assess liver steatosis and fibrosis respectively in NAFLD patients. A quick, straightforward and non-invasive method for NAFLD screening in patients with MetS components is TE-CAP. Once diagnosed, the next step is to determine the presence of fibrosis by LSM which should point out high risk patients. Those patients should be referred to hepatologists. LB may be avoided in a substantial number of patients if TE with CAP is used for screening.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, University Hospital Center Rijeka, 51000 Rijeka, Croatia; School of Medicine, 51000 Rijeka, Croatia
| | | | - Toni Juric
- School of Medicine, 51000 Rijeka, Croatia
| | - Mia Klapan
- School of Medicine, 51000 Rijeka, Croatia
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Nadija Skenderevic
- Department of Gastroenterology, University Hospital Center Rijeka, 51000 Rijeka, Croatia
| | - Sandra Milic
- Department of Gastroenterology, University Hospital Center Rijeka, 51000 Rijeka, Croatia; School of Medicine, 51000 Rijeka, Croatia
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Sinkala E, Vinikoor M, Miyanda Siyunda A, Zyambo K, Besa E, Nsokolo B, Wandeler G, Foster GR, Kelly P. Hepatosplenic schistosomiasis in Zambian adults is characterized by increased liver stiffness: A nested case-control study. Heliyon 2020; 6:e04534. [PMID: 32760834 PMCID: PMC7393539 DOI: 10.1016/j.heliyon.2020.e04534] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 08/20/2019] [Accepted: 07/20/2020] [Indexed: 01/26/2023] Open
Abstract
Cirrhosis commonly complicates portal hypertension worldwide but in Zambia hepatosplenic schistosomiasis (HSS) dominates as the cause of portal hypertension. We need easier and non-invasive ways to assess HSS. Transient elastography (TE), a measure of liver stiffness can diagnose liver cirrhosis. TE remains unexplored in HSS patients, who generally have normal liver parenchyma. We aimed to explore liver stiffness in HSS. This nested case control study was conducted at the University Teaching Hospital, Lusaka, Zambia between January 2015 and January 2016. We enrolled 48 adults with HSS and 22 healthy controls. We assessed liver stiffness using TE while plasma hyaluronan was used to assess liver fibrosis. Plasma tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) were used to assess inflammation. The median (interquartile range) liver stiffness was higher in patients, 9.5 kPa (7.8, 12.8) than in controls, 4.7 kPa (4.0, 5.4), P < 0.0001. We noted linear correlations of hyaluronan and TNFR1 with the liver stiffness, P = 0.0307 and P = 0.0003 respectively. HSS patients seem to have higher liver stiffness than healthy controls. TE may be useful in identifying fibrosis in HSS. The positive correlations of inflammatory markers with TE suggest that HSS has both periportal and parenchymal pathophysiology.
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Affiliation(s)
- Edford Sinkala
- Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia,Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia,Corresponding author.
| | - Michael Vinikoor
- Department of Medicine, University of Alabama at Birmingham, Birmingham, USA,Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
| | | | - Kanekwa Zyambo
- Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia
| | - Ellen Besa
- Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia
| | - Bright Nsokolo
- Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia,Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia
| | - Gilles Wandeler
- Institute of Social and Preventive Medicine, University of Bern, Switzerland,Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Graham R. Foster
- Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK
| | - Paul Kelly
- Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia,Tropical Gastroenterology & Nutritional Group, Department of Internal Medicine, University of Zambia, Lusaka, Zambia,Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK
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Suryadevara V, Nazeer SS, Sreedhar H, Adelaja O, Kajdacsy-Balla A, Natarajan V, Walsh MJ. Infrared spectral microscopy as a tool to monitor lung fibrosis development in a model system. BIOMEDICAL OPTICS EXPRESS 2020; 11:3996-4007. [PMID: 33014581 PMCID: PMC7510888 DOI: 10.1364/boe.394730] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/17/2020] [Accepted: 06/18/2020] [Indexed: 06/11/2023]
Abstract
Tissue fibrosis is a progressive and destructive disease process that can occur in many different organs including the liver, kidney, skin, and lungs. Fibrosis is typically initiated by inflammation as a result of chronic insults such as infection, chemicals and autoimmune diseases. Current approaches to examine organ fibrosis are limited to radiological and histological analyses. Infrared spectroscopic imaging offers a potential alternative approach to gain insight into biochemical changes associated with fibrosis progression. In this study, we demonstrate that IR imaging of a mouse model of pulmonary fibrosis can identify biochemical changes observed with fibrosis progression and the beginning of resolution using K-means analysis, spectral ratios and multivariate data analysis. This study demonstrates that IR imaging may be a useful approach to understand the biochemical events associated with fibrosis initiation, progression and resolution for both the clinical setting and for assessing novel anti-fibrotic drugs in a model system.
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Affiliation(s)
- Vidyani Suryadevara
- Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Shaiju S. Nazeer
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Hari Sreedhar
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Oluwatobi Adelaja
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - André Kajdacsy-Balla
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Viswanathan Natarajan
- Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA
- Contributed equally as senior co-authors
| | - Michael J. Walsh
- Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA
- Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA
- Contributed equally as senior co-authors
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Han XZ, Zhang SF, Yi JY, Wang B, Sun HQ. Effect of FibroScan test in antiviral therapy for HBV-infected patients with ALT <2 upper limit of normal. Open Life Sci 2020; 15:418-422. [PMID: 33817230 PMCID: PMC7874573 DOI: 10.1515/biol-2020-0044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 06/17/2019] [Accepted: 07/03/2019] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE The objective of this study is to detect the liver stiffness of hepatitis B virus (HBV)-infected patients with an alanine aminotransferase (ALT) level of <2 upper limit of normal (2ULN) by FibroScan and compare histological changes to assess the progression of liver lesions and its test results. METHODS There were 36 patients who had a liver FibroScan degree of >7.3 KD (F1), and a liver biopsy was conducted. Along with serology of liver fibrosis, indexes and hierarchical processing were used for evaluation. The correlation between these factors was analyzed. RESULTS The histopathological results of the liver were closely correlated with liver hardness. In the pathological diagnosis of chronic hepatitis, G represents the grade of inflammation and S represents the stage of hepatic fibrosis. Pathological examination results of H&E staining of liver tissue sections revealed that the area under the work characteristic curve of the subjects in G2S1, G2S2, G3S2, and G3S3 stages was 0.923, 0.916, 0.955, and 0.971, respectively, with diagnostic cut-off values of 9.03, 9.85, 15.14, and 30.67, respectively. Furthermore, hydroxyapatite, type III procollagen, laminin, and type IV collagen of serum fibrosis indexes are associated with liver stiffness values (P < 0.05). CONCLUSION FibroScan can be used as an alternative to liver biopsy. It is meaningful in determining whether HBV infected patients with an ALT level of <2 ULN should receive antiviral therapy.
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Affiliation(s)
- Xian-Zhi Han
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Shu-Feng Zhang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Jia-Yin Yi
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Bin Wang
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Hui-Qing Sun
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Tomah S, Alkhouri N, Hamdy O. Nonalcoholic fatty liver disease and type 2 diabetes: where do Diabetologists stand? Clin Diabetes Endocrinol 2020; 6:9. [PMID: 32518675 PMCID: PMC7275502 DOI: 10.1186/s40842-020-00097-1] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/10/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The increasing prevalence of NAFLD mirrors that of obesity and type 2 diabetes over the last two decades. MAIN In a two-way pathophysiologic relationship, NAFLD increases the risk of developing type 2 diabetes, while the latter promotes the progression of simple fatty liver to a more advanced form called nonalcoholic steatohepatitis (NASH). NASH increases the risk of cirrhosis and hepatocellular carcinoma (HCC), which may require liver transplantation. With the absence of FDA-approved medications for NAFLD treatment, lifestyle intervention remains the only therapy. Lately, extensive research efforts have been aimed at modifying NASH fibrosis and developing noninvasive screening methods. CONCLUSION We highlight the pathophysiologic relationships between NAFLD and type 2 diabetes, discuss disease recognition, models of care, and current and emerging therapies for NASH treatment.
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Affiliation(s)
- Shaheen Tomah
- Research Division, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215 USA
- Department of Medicine, Harvard Medical School, Boston, MA 02215 USA
| | - Naim Alkhouri
- Texas Liver Institute, University of Texas (UT) Health, San Antonio, TX USA
| | - Osama Hamdy
- Research Division, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215 USA
- Department of Medicine, Harvard Medical School, Boston, MA 02215 USA
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Wu HC, Huang CL, Wang HW, Hsu WF, Tsai TY, Chen SH, Peng CY. Serum miR-21 correlates with the histological stage of chronic hepatitis B-associated liver fibrosis. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2019; 12:3819-3829. [PMID: 31933770 PMCID: PMC6949750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 08/29/2019] [Indexed: 06/10/2023]
Abstract
This study aimed to investigate the correlation between serum microRNA levels and histological stages of liver fibrosis in patients with chronic hepatitis B (CHB). A total of 28 patients with CHB who received liver biopsy at China Medical University Hospital between October 2012 and April 2013 were included in the study. The patients were divided into four groups according to the histological stages of liver fibrosis by using the METAVIR score. Serum microRNA levels were tested using quantitative real-time PCR after microRNA extraction from patients' serum. Of all the tested microRNAs, miR-21, miR-29, and miR-221 were expressed in the serum. The expression levels of serum miR-21 were significantly correlated with liver fibrosis stages (r = 0.420, P = 0.026). The expression levels of serum miR-21 were significantly correlated with cirrhosis (METAVIR F4 vs. F1-F3, r = 0.386, P = 0.043). The grades of serum miR-21 showed significant ordered differences among different stages of liver fibrosis (P = 0.019). However, miR-21 exhibited an inferior predictive performance for liver fibrosis F2-F4 (AUROC = 0.69) compared with other noninvasive markers of liver fibrosis, namely the aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score (AUROC = 0.83 and 0.86, respectively). Serum miR-21 correlated with the histological stage of liver fibrosis in patients with CHB. The predictive performance of serum miR-21 for the histological stage of liver fibrosis tended to be inferior to those of the APRI and FIB-4 score.
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Affiliation(s)
- Hsien-Chih Wu
- Graduate Institute of Biomedical Sciences, China Medical UniversityTaichung 40402, Taiwan
- Department of Gastroenterology and Hepatology, Yuanlin Christian HospitalChanghua 40402, Taiwan
| | - Chia-Lin Huang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University HospitalTaichung 40402, Taiwan
| | - Hung-Wei Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University HospitalTaichung 40402, Taiwan
| | - Wei-Fan Hsu
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University HospitalTaichung 40402, Taiwan
| | - Tsung-Yu Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University HospitalTaichung 40402, Taiwan
| | - Sheng-Hung Chen
- School of Medicine, China Medical UniversityTaichung 40402, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University HospitalTaichung 40402, Taiwan
| | - Cheng-Yuan Peng
- School of Medicine, China Medical UniversityTaichung 40402, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University HospitalTaichung 40402, Taiwan
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27
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ND AM. Non-Alcoholic Fatty Liver Disease, an Overview. Integr Med (Encinitas) 2019; 18:42-49. [PMID: 31341444 PMCID: PMC6601444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects 25% of people worldwide. Patients with fatty liver disease are primarily asymptomatic. Currently, specialists are predicting that fatty liver related cirrhosis will the be leading reason for liver transplants in the next 10-20 years, displacing hepatitis C and alcohol related liver transplants. NAFLD exists on a spectrum of simple steatosis to steatosis with inflammation and different levels of fibrosis. It is currently estimated that 20% of simple steatosis patients will progress to nonalcoholic steatohepatitis (NASH). Patients with NASH are at risk for further progression to cirrhosis and hepatocellular carcinoma. There is no single factor that triggers progression from simple steatosis to NASH, however, we do know that NASH is more prevalent in patients with obesity, diabetes, and metabolic syndrome. NAFLD is thought to be the hepatic manifestation of metabolic syndrome, and is closely tied with hyperinsulinemia. Currently there are no approved FDA treatments for NAFLD. NAFLD is typically found incidentally on imaging such as abdominal ultrasound and CT. Elevations in alanine aminotransferase (ALT) may prompt the clinician to evaluate for NAFLD however ALT should not be used as a diagnostic tool. The gold standard for diagnosis of NAFLD and NASH is a liver biopsy. Only a liver biopsy can distinguish simple steatosis from NASH. In patients whom NAFLD is suspected, appropriate biochemical assessment and imaging should be evaluated. Also, the presence of fibrosis should be assessed. Weight loss and dietary modifications are currently the only recommendations provided to NAFLD patients. There is histological improvement seen in in patients whom lose 5-10% of their body weight. Certain dietary factors play a role in the development of NAFLD including excessive caloric intake and high fructose consumption. There are pharmacological treatments currently being studied as well as non-pharmacological agents. This overview focuses on evaluation, management and treatments in NAFLD.
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Can obesity-induced inflammation in skeletal muscle and intramuscular adipose tissue accurately detect liver fibrosis? JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS 2018; 18:509-524. [PMID: 30511955 PMCID: PMC6313048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVES Obesity is characterized by a chronic, low grade, systemic inflammation. However, little is known about the role of skeletal muscle, which represents an active metabolic organ whose activities need to be determined. The purpose of our study was to detect relationships between skeletal muscle and adipose tissue inflammation with nonalcoholic fatty liver disease (NAFLD) and diabetes, as well as to explore associations with clinicopathological parameters. METHODS Our study population consisted of 50 morbidly obese patients undergoing planned bariatric surgery. Biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver. The expression of CD68 and CD3 was assessed by immunohistochemistry. RESULTS Our findings suggest a complex inter- and intra-tissue co-expression network that links obesity-induced inflammation in adipose depots and skeletal muscle with NAFLD. A novel finding is the intricate cross-talk between SM, EMAT and the liver and the probable correlation between SM, EMAT inflammation and the presence of liver fibrosis. CONCLUSIONS Although the mechanisms of obesity-induced inflammation and its association with NAFLD and liver fibrosis are incompletely understood, our findings indicate an extensive and complex tissue network that needs to be further investigated.
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Lam S, Nettel-Aguirre A, Van Biervliet S, Roeb E, Sadler MD, Friedrich-Rust M, Karlas T, Kitson MT, deBruyn JCC. Transient Elastography in the Evaluation of Cystic Fibrosis-Associated Liver Disease: Systematic Review and Meta-analysis. J Can Assoc Gastroenterol 2018; 2:71-80. [PMID: 31294368 PMCID: PMC6507293 DOI: 10.1093/jcag/gwy029] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background and aims Complications of cystic fibrosis-associated liver disease (CFLD) are a leading nonpulmonary cause of death. Transient elastography (TE) has recently been investigated to detect CFLD. This study reviews the current literature for TE in the detection CFLD. A meta-analysis was performed to determine the ideal liver stiffness measurement (LSM) cutoff. Methods PubMed, Medline, EMBASE and Web of Science were searched from inception until April 2016 for publications involving the detection of CFLD with TE. Data were extracted using a fixed protocol (a priori design) including study design, population characteristics, probe size and AST Platelet Ratio Index (APRI). Results Diagnostic properties were summarized from six studies of 605 patients. Cutoff for LSM was determined using pooled data submitted by authors. The cutoff for LSM and APRI were ≥5.95 kPa and ≥0.329 respectively, yielding a sensitivity, specificity and area under receiver operator characteristic of 55%, 87%, 0.76, 52%, 93% and 0.84 for LSM and APRI, respectively. When LSM ≥5.95 kPa and APRI ≥0.329, the sensitivity, specificity, positive predictive value and negative predictive value were 43%, 99%, 92% and 87% with a diagnostic odds ratio of 74.9. A bivariate metaregression model showed that pediatric specific cutoffs for liver stiffness and APRI may not be necessary. Conclusion Individually, LSM and APRI have poor sensitivity but good specificity for detecting CFLD. They are most useful when combined. We propose that patients with LSM ≥5.95 kPa and APRI ≥0.329 be investigated thoroughly for the presence of cystic fibrosis-associated liver disease.
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Affiliation(s)
- Simon Lam
- Alberta Children's Hospital, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
| | - Alberto Nettel-Aguirre
- Alberta Children's Hospital, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.,Alberta Children's Hospital, Community Health Sciences, Calgary, Alberta, Canada
| | | | - Elke Roeb
- University Hospital, Gastroenterology, Justus-Liebig-University Giessen, Giessen, Germany
| | | | - Mireen Friedrich-Rust
- J.W. Goethe University Hospital, Department of Internal Medicine, Goethe University Hospital, Frankfurt, Germany
| | - Thomas Karlas
- University of Leipzig, Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
| | - Matthew T Kitson
- Alfred Hospital, Gastroenterology, Alfred Hospital, Australia and Monash University, Melbourne, Victoria, Australia
| | - Jennifer C C deBruyn
- Alberta Children's Hospital, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
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Dong Y, Potthoff A, Klinger C, Barreiros AP, Pietrawski D, Dietrich CF. Ultrasound findings in autoimmune hepatitis. World J Gastroenterol 2018; 24:1583-1590. [PMID: 29686465 PMCID: PMC5910541 DOI: 10.3748/wjg.v24.i15.1583] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 03/20/2018] [Accepted: 03/30/2018] [Indexed: 02/06/2023] Open
Abstract
Ultrasound findings in autoimmune hepatitis (AIH) have not been reported systematically so far. The use of reliable and accurate noninvasive methods for determining fibrosis stage is important in evaluation of treatment efficacy and fibrosis regression in AIH. Imaging plays an important role in detection of complications and ruling out other possible causes of chronic liver diseases. Ultrasound elastography cut-off values in AIH patients are not the same as those in patients with chronic viral hepatitis or non-alcoholic fatty liver disease. AIH is characterized by wide fluctuations in inflammatory activity. Here we report on current knowledge of ultrasound findings in AIH.
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Affiliation(s)
- Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Andrej Potthoff
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover D-30625, Germany
| | - Christoph Klinger
- Department of Internal Medicine 1, Klinikum Ludwigsburg, Ludwigsburg D-71634, Germany
| | - Ana Paula Barreiros
- German Organ Transplantation Foundation, Region Mitte, Mainz D-55131, Germany
| | - Dariusz Pietrawski
- Department of Internal Medicine 2, Caritas-Krankenhaus Bad Mergentheim, Bad Mergentheim D-97980, Germany
| | - Christoph F Dietrich
- Department of Internal Medicine 2, Caritas-Krankenhaus Bad Mergentheim, Bad Mergentheim D-97980, Germany
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Abstract
Patients with HIV have a proclivity to develop liver fibrosis, especially when associated with other conditions such as HCV, HBV, and NAFLD. Identifying HIV-infected patients with significant fibrosis or cirrhosis plays an important role in clinical and therapeutic decision-making. Liver biopsy is currently considered as the gold standard for fibrosis assessment but carries many shortcomings (cost, invasiveness, complications, false negative rate of 20 %). Multiple non-invasive methods of liver fibrosis assessment have been developed, but not all have been studied in HIV-infected individuals. Non-invasive liver fibrosis tools include both serologic-based testing scores (rely on direct and/or indirect markers) such as APRI, FIB4, FibroTest, FibroSpect II, HepaScore, or imaging-based methods such as vibration controlled liver elastography. There is validated data to support the use of non-invasive modalities of fibrosis assessment in HIV-HCV co-infected individuals for the exclusion of cirrhosis, but may be poorly reliable or not enough data exists for the assessment of other co-morbid disease processes.
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Pan AN, Xu WW, Luo YL, Yu HH, Hu YB, Sun QF, Ding JG, Wu YH. A novel system for predicting liver histopathology in patients with chronic hepatitis B. Medicine (Baltimore) 2017; 96:e6465. [PMID: 28383410 PMCID: PMC5411194 DOI: 10.1097/md.0000000000006465] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
There is currently a lack of reliable, reproducible, and easily applied methods for assessing changes in liver histology in patients in the gray zone phase of chronic hepatitis B (CHB). Therefore, we aimed to develop a novel predictive scoring system to detect significant liver histological changes in these patients.A total of 388 patients in the gray zone phase of CHB who underwent liver biopsy were divided into a training group and a validation group, and their clinical and routinely available laboratory parameters were analyzed using univariate analysis, Spearman correlation analysis, and logistic modeling. A novel scoring system, termed the Significant Histological Model (SHM), was constructed using logistic modeling. The diagnostic accuracy of our novel scoring system was evaluated by the receiving operating characteristic (ROC) method, sensitivity, specificity, and positive and negative predictive values (NPVs).We established the novel SHM scoring system using serum aspartate transaminase (AST), platelet counts (PLTs), albumin (ALB), and hepatitis B virus (HBV) DNA (log10 IU/mL) levels. The area under the ROC curve of the SHM scoring system was 0.763 in the training group and 0.791 in the validation group. For patients with a score of -1.0 or less and no significant histological changes, the sensitivity was 78.9%, specificity was 51.5%, positive predictive value (PPV) was 46.4%, and NPV was 82.0%. In the validation set, the sensitivity, specificity, PPV, and NPV were 80.0%, 66.6%, 56.3%, and 86.2%, respectively.This novel scoring system using AST, PLT, ALB, and HBV DNA (log10 IU/mL) levels identifies patients in the gray zone phase of CHB with and without histological changes with a high degree of accuracy. Here, we provide the experimental basis for the initiation of clinical antiviral treatment without the need for liver biopsy.
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Affiliation(s)
- An-Na Pan
- Department of Infection, The Third Affiliated Hospital of Wenzhou Medical University, Ruian
| | - Wang-Wang Xu
- Department of Infection, Wenzhou People's Hospital
| | - Yun-Lin Luo
- Department of Infection, The Third Affiliated Hospital of Wenzhou Medical University, Ruian
| | - Huan-Huan Yu
- Department of Infection, The Third Affiliated Hospital of Wenzhou Medical University, Ruian
| | - Yi-Bing Hu
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Qing-Feng Sun
- Department of Infection, The Third Affiliated Hospital of Wenzhou Medical University, Ruian
| | - Ji-Guang Ding
- Department of Infection, The Third Affiliated Hospital of Wenzhou Medical University, Ruian
| | - Yang-He Wu
- Department of Infection, The Third Affiliated Hospital of Wenzhou Medical University, Ruian
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Torres-Valadez R, Roman S, Jose-Abrego A, Sepulveda-Villegas M, Ojeda-Granados C, Rivera-Iñiguez I, Panduro A. Early Detection of Liver Damage in Mexican Patients with Chronic Liver Disease. J Transl Int Med 2017; 5:49-57. [PMID: 28680839 PMCID: PMC5490962 DOI: 10.1515/jtim-2017-0003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Liver cirrhosis is usually detected at the later stages of disease. This study is aimed to detect liver damage in patients with chronic liver disease using transitional elastography (TE) and to assess the biochemical parameters associated with liver damage. METHODS In 578 patients, chronic liver disease based on etiology was diagnosed by clinical and laboratory tests. Liver damage was evaluated with TE (FibroScan®), while its association with biochemical parameters was performed using the logistic regression tests. RESULTS Overall, the main etiologies of liver damage were hepatitis C virus (HCV) (37%), alcoholic liver disease (ALD) (33%) and non-alcoholic steatohepatitis (NASH) (26%). Patients were 40 to 50 years of age. ALD and hepatitis B prevailed in men, whereas HCV and NASH in women. The stages of fibrosis were F0 (n = 121, 21%), F1 (n = 122, 21%), F2 (n = 58, 10%), F3 (n = 46, 8%) and F4 (n = 87, 15%). In patients with liver cirrhosis, ALD (n = 96/217, 45%), HCV (n = 94/217, 43%) and NASH (n = 21/217, 10%) were the leading etiologies. Platelets count (OR=3.31, 95%CI 1.61-6.78), glucose (OR=3.07, 95%CI 1.50-6.26), gamma-glutamyl-transferase (OR=3.60, 95%CI 1.79-7.25), albumin (OR=3.89, 95%CI 1.61-9.36), and total bilirubin (OR=3.93, 95%CI 1.41-10.91) were associated to advanced stages of fibrosis (F3-F4) regardless of etiology. The concordance and positive predictive values of these parameters were higher as compared to other scores. CONCLUSION Asymptomatic liver disease due to HCV, ALD and NASH prevailed in young adults. Advanced liver damage assessed by TE was associated with five biochemical parameters. In conjunction, both methodologies may be useful for the early detection of fibrosis and cirrhosis in Latin America.
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Affiliation(s)
- Rafael Torres-Valadez
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Sonia Roman
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Alexis Jose-Abrego
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Maricruz Sepulveda-Villegas
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Claudia Ojeda-Granados
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Ingrid Rivera-Iñiguez
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
| | - Arturo Panduro
- Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, “Fray Antonio Alcalde”, Mexico and Health Sciences Center, University of Guadalajara, Guadalajara, Jalisco, Mexico
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Alkhouri N, Feldstein AE. Noninvasive diagnosis of nonalcoholic fatty liver disease: Are we there yet? Metabolism 2016; 65:1087-95. [PMID: 26972222 PMCID: PMC4931968 DOI: 10.1016/j.metabol.2016.01.013] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 12/22/2015] [Accepted: 01/07/2016] [Indexed: 12/15/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in the United States affecting approximately 80-100 million Americans. NAFLD includes a spectrum of diseases ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to fibrosis and eventually cirrhosis. Patients with NASH and significant fibrosis on liver biopsy have an increased risk for liver-related morbidity and mortality compared to those with NAFL. Due to the high prevalence of NAFLD and its progressive nature, there has been an urgent need to develop reliable noninvasive tests that can accurately predict the presence of advanced disease without the need for liver biopsy. These tests can be divided into those that predict the presence of NASH and those that predict the presence of fibrosis. In this review, we provide a concise overview of different noninvasive methods for staging the severity of NAFLD.
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Affiliation(s)
- Naim Alkhouri
- Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA; Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ariel E Feldstein
- Department of Pediatrics, University of California San Diego (UCSD), CA, USA.
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Friedli I, Crowe LA, Berchtold L, Moll S, Hadaya K, de Perrot T, Vesin C, Martin PY, de Seigneux S, Vallée JP. New Magnetic Resonance Imaging Index for Renal Fibrosis Assessment: A Comparison between Diffusion-Weighted Imaging and T1 Mapping with Histological Validation. Sci Rep 2016; 6:30088. [PMID: 27439482 PMCID: PMC4954968 DOI: 10.1038/srep30088] [Citation(s) in RCA: 118] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 06/29/2016] [Indexed: 12/12/2022] Open
Abstract
A need exists to noninvasively assess renal interstitial fibrosis, a common process
to all kidney diseases and predictive of renal prognosis. In this translational
study, Magnetic Resonance Imaging (MRI) T1 mapping and a new segmented
Diffusion-Weighted Imaging (DWI) technique, for Apparent Diffusion Coefficient
(ADC), were first compared to renal fibrosis in two well-controlled animal models to
assess detection limits. Validation against biopsy was then performed in 33 kidney
allograft recipients (KARs). Predictive MRI indices, ΔT1 and
ΔADC (defined as the cortico-medullary differences), were compared to
histology. In rats, both T1 and ADC correlated well with fibrosis and inflammation
showing a difference between normal and diseased kidneys. In KARs, MRI indices were
not sensitive to interstitial inflammation. By contrast, ΔADC
outperformed ΔT1 with a stronger negative correlation to fibrosis
(R2 = 0.64 against
R2 = 0.29
p < 0.001). ΔADC tends to negative values
in KARs harboring cortical fibrosis of more than 40%. Using a discriminant analysis
method, the ΔADC, as a marker to detect such level of fibrosis or
higher, led to a specificity and sensitivity of 100% and 71%, respectively. This new
index has potential for noninvasive assessment of fibrosis in the clinical
setting.
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Affiliation(s)
- I Friedli
- Division of Radiology, Department of Radiology and Medical Informatics Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
| | - L A Crowe
- Division of Radiology, Department of Radiology and Medical Informatics Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
| | - L Berchtold
- Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals, University of Geneva, Faculty of Medicine, Geneva, Switzerland
| | - S Moll
- Division of Pathology, Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
| | - K Hadaya
- Divisions of Nephrology and Transplantation, Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
| | - T de Perrot
- Division of Radiology, Department of Radiology and Medical Informatics Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
| | - C Vesin
- Division of Cell Physiology and Metabolism, Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
| | - P-Y Martin
- Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals, University of Geneva, Faculty of Medicine, Geneva, Switzerland
| | - S de Seigneux
- Service of Nephrology, Department of Internal Medicine Specialties, Geneva University Hospitals, University of Geneva, Faculty of Medicine, Geneva, Switzerland
| | - J-P Vallée
- Division of Radiology, Department of Radiology and Medical Informatics Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland
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Behairy BES, Sira MM, Zalata KR, Salama ESE, Abd-Allah MA. Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter? World J Gastroenterol 2016; 22:4238-4249. [PMID: 27122674 PMCID: PMC4837441 DOI: 10.3748/wjg.v22.i16.4238] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 03/04/2016] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases. METHODS A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected. RESULTS The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P < 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 ± 7.23 kPa) compared to Wilson disease (8.30 ± 0.84 kPa) and HCV groups (7.43 ± 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable associated with higher LSM (P < 0.0001). CONCLUSION TE appears reliable in distinguishing different stages of liver fibrosis in children. However, its values vary according to the disease type. For that, a disease-specific estimation of cut-off values for fibrosis staging is worthy.
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Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics. PLoS One 2016; 11:e0146588. [PMID: 26735954 PMCID: PMC4703410 DOI: 10.1371/journal.pone.0146588] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 12/18/2015] [Indexed: 12/19/2022] Open
Abstract
Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G’ and G” and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.
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Assessment of Liver Stiffness in Pediatric Fontan Patients Using Transient Elastography. Can J Gastroenterol Hepatol 2016; 2016:7125193. [PMID: 27656638 PMCID: PMC5021462 DOI: 10.1155/2016/7125193] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/11/2016] [Indexed: 01/09/2023] Open
Abstract
Background. Hepatic fibrosis is a potential complication following Fontan surgery and heralds long-term risk for cirrhosis. Transient elastography (TE) is a rapid, noninvasive method to assess liver fibrosis by measuring liver stiffness. Objectives. To compare liver stiffness and liver biochemistries in pediatric Fontan patients with age- and sex-matched controls and to determine patients' acceptance of TE. Methods. Patients were recruited from British Columbia Children's Hospital. Twenty-two Fontan patients (15 males) were identified. Demographic information and cardiac data were collected. TE was measured using size-appropriate probes. Results. The median age of the Fontan cohort was 13.7 (5.9-16.8) years. Time from Fontan surgery to TE was 9.6 (1.0-12.9) years. The median Fontan circuit pressure was 13 (11-14) mmHg. TE values were higher in Fontan patients versus controls (18.6 versus 4.7 kPa, p < 0.001). There was no association between TE values and patient age (r = 0.41, p = 0.058), time since Fontan surgery (r = 0.40, p = 0.062), or median Fontan circuit pressure (CVP) (r = 0.35, p = 0.111). Patients found TE to be nonpainful, convenient, and safe. Conclusions. TE is feasible to assess liver stiffness in children following Fontan surgery. Pediatric Fontan patients have markedly elevated liver stiffness values. TE may have important utility in liver care follow-up of pediatric Fontan patients.
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Zeng X, Xu C, He D, Li M, Zhang H, Wu Q, Xiang D, Wang Y. Performance of several simple, noninvasive models for assessing significant liver fibrosis in patients with chronic hepatitis B. Croat Med J 2015; 56:272-279. [PMID: 26088852 PMCID: PMC4500965 DOI: 10.3325/cmj.2015.56.272] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 02/10/2015] [Indexed: 12/20/2022] Open
Abstract
AIM To compare the performance of several simple, noninvasive models comprising various serum markers in diagnosing significant liver fibrosis in the same sample of patients with chronic hepatitis B (CHB) with the same judgment standard. METHODS A total of 308 patients with CHB who had undergone liver biopsy, laboratory tests, and liver stiffness measurement (LSM) at the Southwest Hospital, Chongqing, China between March 2010 and April 2014 were retrospectively studied. Receiver operating characteristic (ROC) curves and area under ROC curves (AUROCs) were used to analyze the results of the models, which incorporated age-platelet (PLT) index (API model), aspartate transaminase (AST) to alanine aminotransferase (ALT) ratio (AAR model), AST to PLT ratio index (APRI model), γ-glutamyl transpeptidase (GGT) to PLT ratio index (GPRI model), GGT-PLT-albumin index (S index model), age-AST-PLT-ALT index (FIB-4 model), and age-AST-PLT-ALT-international normalized ratio index (Fibro-Q model). RESULTS The AUROCs of the S index, GPRI, FIB-4, APRI, API, Fibro-Q, AAR, and LSM for predicting significant liver fibrosis were 0.726 (P<0.001), 0.726 (P<0.001), 0.621 (P=0.001), 0.619 (P=0.001), 0.580 (P=0.033), 0.569 (P=0.066), 0.495 (P=0.886), and 0.757 (P<0.001), respectively. The S index and GPRI had the highest correlation with histopathological scores (r=0.373, P<0.001; r=0.372, P<0.001, respectively) and LSM values (r=0.516, P<0.001; r=0.513, P<0.001, respectively). When LSM was combined with S index and GPRI, the AUROCs were 0.753 (P<0.001) and 0.746 (P<0.001), respectively. CONCLUSION S index and GPRI had the best diagnostic performance for significant liver fibrosis and were robust predictors of significant liver fibrosis in patients with CHB for whom transient elastography was unavailable.
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Affiliation(s)
| | | | | | | | | | | | | | - Yuming Wang
- Yuming Wang, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China,
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Patel K, Wilder J. Fibroscan. Clin Liver Dis (Hoboken) 2014; 4:97-101. [PMID: 30992931 PMCID: PMC6448744 DOI: 10.1002/cld.407] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 06/14/2014] [Accepted: 06/20/2014] [Indexed: 02/04/2023] Open
Affiliation(s)
- Keyur Patel
- Duke Clinical Research Institute and Duke University Medical CenterDurhamNC
| | - Julius Wilder
- Duke Clinical Research Institute and Duke University Medical CenterDurhamNC
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