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Song J, Chen S, Qian K, Ye W. Association of ultra-processed foods consumption with increased liver steatosis in U.S. adults. Front Nutr 2025; 12:1536989. [PMID: 40151346 PMCID: PMC11948534 DOI: 10.3389/fnut.2025.1536989] [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: 11/29/2024] [Accepted: 02/26/2025] [Indexed: 03/29/2025] Open
Abstract
Background Recent studies demonstrated a strong association between dietary habits and liver health, particularly in the development of steatosis and fibrosis. This study aimed to examine the impact of ultra-processed foods (UPFs) on liver health, focusing specifically on their influence on the risks of liver steatosis and fibrosis. Methods A cross-sectional analysis was conducted on 4,992 participants aged 18 years and older from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Dietary intake was assessed using one or two 24-h dietary recalls, and foods were categorized by their processing level using the NOVA classification system. UPFs consumption was measured in grams and divided into quartiles. Liver health was assessed using controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) via elastography, to evaluate steatosis and fibrosis, respectively. Linear regression models were applied to assess the relationship between UPFs consumption and liver outcomes, adjusting for sociodemographic (age, sex, ethnicity), lifestyle (alcohol consumption, physical activity), and biomedical factors (liver enzyme levels). Results Higher UPF intake was significantly associated with increased CAP values, indicating a higher risk of liver steatosis. While liver fibrosis, measured by LSM, was also associated with UPF consumption, this relationship did not reach statistical significance. Multivariate analysis showed that increased UPF consumption did not significantly affect LSM (p = 0.110) but was strongly associated with elevated CAP values (p = 0.009). In participants with fatty liver (CAP > 248 dB/m), the association between UPF intake and CAP remained significant (p = 0.020). Participants in the highest quartile of UPFs consumption (Q4) exhibited higher CAP values compared to those in the lowest quartile (Q1) (β = 1.22; 95% CI: 1.02, 1.47). Stratified analysis revealed that the association between UPF intake and CAP was more pronounced in obese individuals (HR = 1.08, 95% CI: 1.03-1.15, p = 0.022) and those with high waist circumference (HR = 1.06, 95% CI: 1.01-1.10, p = 0.032). Conclusion These results underscore the adverse impact of UPFs on liver health, particularly by increasing steatosis, while the connection with fibrosis remains less straightforward.
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Affiliation(s)
- Jingru Song
- Department of Gastroenterology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Siqi Chen
- Department of Gastroenterology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Kexin Qian
- Department of Gastroenterology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, China
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wei Ye
- Department of Gastroenterology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Schäfer H, Lajmi N, Valente P, Pedrioli A, Cigoianu D, Hoehne B, Schenk M, Guo C, Singhrao R, Gmuer D, Ahmed R, Silchmüller M, Ekinci O. The Value of Clinical Decision Support in Healthcare: A Focus on Screening and Early Detection. Diagnostics (Basel) 2025; 15:648. [PMID: 40075895 PMCID: PMC11899545 DOI: 10.3390/diagnostics15050648] [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: 11/15/2024] [Revised: 02/18/2025] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
In a rapidly changing technology landscape, "Clinical Decision Support" (CDS) has become an important tool to improve patient management. CDS systems offer medical professionals new insights to improve diagnostic accuracy, therapy planning, and personalized treatment. In addition, CDS systems provide cost-effective options to augment conventional screening for secondary prevention. This review aims to (i) describe the purpose and mechanisms of CDS systems, (ii) discuss different entities of algorithms, (iii) highlight quality features, and (iv) discuss challenges and limitations of CDS in clinical practice. Furthermore, we (v) describe contemporary algorithms in oncology, acute care, cardiology, and nephrology. In particular, we consolidate research on algorithms across diseases that imply a significant disease and economic burden, such as lung cancer, colorectal cancer, hepatocellular cancer, coronary artery disease, traumatic brain injury, sepsis, and chronic kidney disease.
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Affiliation(s)
- Hendrik Schäfer
- Clinical Development & Medical Affairs, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland (R.S.)
- Medical Faculty, Friedrich Schiller University Jena, 07737 Jena, Germany
| | - Nesrine Lajmi
- Clinical Value & Validation, Roche Information Solutions, 2881 Scott Blvd, Santa Clara, CA 95050, USA
| | - Paolo Valente
- Clinical Development & Medical Affairs, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland (R.S.)
| | - Alessandro Pedrioli
- Clinical Value & Validation, Roche Information Solutions, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland
| | - Daniel Cigoianu
- Clinical Development & Medical Affairs, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland (R.S.)
| | - Bernhard Hoehne
- Clinical Development & Medical Affairs, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland (R.S.)
| | - Michaela Schenk
- Quality & Regulatory Roche Information Solutions, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland
| | - Chaohui Guo
- Clinical Value & Validation, Roche Information Solutions, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland
| | - Ruby Singhrao
- Clinical Development & Medical Affairs, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland (R.S.)
| | - Deniz Gmuer
- Healthcare Insights, Roche Information Solutions, Roche Diagnostics International Ltd., Forrenstrasse 2, 6343 Rotkreuz, Switzerland
| | - Rezwan Ahmed
- Data, Analytics & Research, Roche Information Solutions, 2881 Scott Blvd, Santa Clara, CA 95050, USA
| | - Maximilian Silchmüller
- Medical Faculty, Friedrich Schiller University Jena, 07737 Jena, Germany
- Wiener Gesundheitsverbund, Klinik Landstraße, Juchgasse 25, 1030 Vienna, Austria
| | - Okan Ekinci
- Digital Technology & Health Information, Roche Information Solutions, 2841 Scott Blvd, Santa Clara, CA 95050, USA
- School of Medicine, University College Dublin, D04 C1P1 Dublin, Ireland
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Wang Y, Song SJ, Jiang Y, Lai JCT, Wong GLH, Wong VWS, Yip TCF. Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol 2025; 31:S51-S75. [PMID: 38934108 PMCID: PMC11925434 DOI: 10.3350/cmh.2024.0246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 06/26/2024] [Indexed: 06/28/2024] Open
Abstract
In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.
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Affiliation(s)
- Yue Wang
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Sherlot Juan Song
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Yichong Jiang
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Jimmy Che-To Lai
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Lai-Hung Wong
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Terry Cheuk-Fung Yip
- Medical Data Analytic Center, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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Liu L, Zhang D, Fan R, Cheng S, Yang J, Ma L, Ling Z, Zhang Y, Hou J, Wang X, Sun B, Niu J. Serum ECM1 is a promising biomarker for staging and monitoring fibrosis in patients with chronic hepatitis B. SCIENCE CHINA. LIFE SCIENCES 2025; 68:431-440. [PMID: 39348048 DOI: 10.1007/s11427-024-2691-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 07/23/2024] [Indexed: 10/01/2024]
Abstract
It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl4-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.
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Affiliation(s)
- Lian Liu
- Shanghai Institute of Biochemistry and Cell Biology, Centre for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Danyan Zhang
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
| | - Rong Fan
- Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Shipeng Cheng
- Shanghai Institute of Biochemistry and Cell Biology, Centre for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Jichao Yang
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
| | - Liyan Ma
- Shanghai Institute of Biochemistry and Cell Biology, Centre for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Zhiyang Ling
- Shanghai Institute of Biochemistry and Cell Biology, Centre for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Yaguang Zhang
- Med-X Institute, Centre for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, 710061, China.
| | - Jinlin Hou
- Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Xiaomei Wang
- Hepatology Department, Centre of Infectious Diseases and Pathogen Biology, First Hospital of Jilin University, Changchun, 130021, China.
| | - Bing Sun
- Shanghai Institute of Biochemistry and Cell Biology, Centre for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
- School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
| | - Junqi Niu
- Hepatology Department, Centre of Infectious Diseases and Pathogen Biology, First Hospital of Jilin University, Changchun, 130021, China.
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Khan F, Dsouza S, Khamis AH, Abdul F, Farooqi MH, Sulaiman F, Mulla F, Al Awadi F, Hassanein M, Bayoumi R. Noninvasive Assessment of the Severity of Liver Fibrosis in MASLD Patients with Long-Standing Type 2 Diabetes. J Gen Intern Med 2025:10.1007/s11606-025-09348-2. [PMID: 39841343 DOI: 10.1007/s11606-025-09348-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 12/30/2024] [Indexed: 01/23/2025]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), which have a reciprocal relationship compounded by obesity, are highly prevalent in the Middle East affecting morbidity, mortality, and healthcare costs. OBJECTIVE This study aimed to assess the severity of MASLD and liver fibrosis among adult Emirati patients with long-standing T2DM. DESIGN AND PARTICIPANTS This cross-sectional study used noninvasive methods to assess the severity of MASLD and fibrosis progression in an adult cohort of Emirati patients (N = 546) with a mean T2DM duration of 16 years. MAIN MEASURES Fatty liver infiltration was assessed by hepatic steatosis index (HSI), while fibrosis was assessed by the fibrosis-4 (FIB-4) index and aspartate aminotransferase/platelet ratio index (APRI). Of those, 108 patients were randomly subjected to ultrasound-based FibroScan® to assess controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). KEY RESULTS All patients had fatty liver with ~ 83% being categorized as having severe steatosis. Serum-based fibrosis biomarker panels detected significant liver fibrosis in ~ 2.5% of these patients. The APRI appeared to be more restrictive in detecting moderate fibrosis (1.5%) than the FIB-4 index (25.5%). CAP significantly correlated with the LSM, indicating that the two methods contributed to the same underlying pathophysiology. Liver steatosis was more severe in female patients, who were older and had a higher body mass index (BMI) than those with moderate or no significant fibrosis. They also had higher serum liver enzymes and were more likely to have age-related changes in kidney function. Interestingly, severity of both steatosis and fibrosis remained unaffected by age and duration of T2D except for fibrosis severity detected by FibroScan®. CONCLUSIONS This study highlights the critical need for routine screening of MASLD among Emirati patients with long-standing T2DM, given the high point prevalence of severe steatosis (~ 83%), predominantly among women in this population.
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Affiliation(s)
- Farooq Khan
- Hepatology, King's College Hospital London, Dubai, United Arab Emirates
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Stafny Dsouza
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Amar Hassan Khamis
- Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Fatima Abdul
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | | | - Fatima Sulaiman
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Fahad Mulla
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Fatheya Al Awadi
- Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates
| | - Mohammed Hassanein
- Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates
| | - Riad Bayoumi
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
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Liu S, Wan H, Yang L, Shen J, Qi X. High prevalence of steatotic liver disease and fibrosis in the general population: A large prospective study in China. J Hepatol 2025; 82:e23-e25. [PMID: 39084473 DOI: 10.1016/j.jhep.2024.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/02/2024]
Affiliation(s)
- Shanghao Liu
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China; Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China
| | - Heng Wan
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Guangdong, China
| | - Ling Yang
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China
| | - Jie Shen
- Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Guangdong, China.
| | - Xiaolong Qi
- Liver Disease Center of Integrated Traditional Chinese and Western Medicine, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Nanjing, China; Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University; State Key Laboratory of Digital Medical Engineering, Nanjing, China.
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Kobayashi T, Nakatsuka T, Sato M, Soroida Y, Hikita H, Gotoh H, Iwai T, Tateishi R, Kurano M, Fujishiro M. Diagnostic performance of two-dimensional shear wave elastography and attenuation imaging for fibrosis and steatosis assessment in chronic liver disease. J Med Ultrason (2001) 2025; 52:95-103. [PMID: 38951430 PMCID: PMC11799025 DOI: 10.1007/s10396-024-01473-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/14/2024] [Indexed: 07/03/2024]
Abstract
PURPOSE We investigated the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) and attenuation imaging (ATI) in detecting fibrosis and steatosis in patients with chronic liver disease (CLD), comparing them with established methods. METHODS In 190 patients with CLD, 2D-SWE and vibration-controlled transient elastography (VCTE) were used for liver stiffness measurement (LSM), and ATI and controlled attenuation parameter (CAP) were used for steatosis quantification. The correlations between these new and established methods were analyzed. RESULTS Significant correlations were found between 2D-SWE and VCTE (r = 0.78, P < 0.001), and between ATI and CAP (r = 0.70, P < 0.001). Liver stiffness tended to be lower with 2D-SWE compared with that with VCTE, especially in cases with higher LSM, and ATI was less influenced by skin-capsular distance than CAP. Area under the receiver-operating characteristics curves (AUCs) and optimal cut-offs of 2D-SWE for diagnosing liver fibrosis stages F2, F3, and F4 were 0.73 (8.7 kPa), 0.79 (9.1 kPa), and 0.88 (11.6 kPa), respectively. The AUCs and optimal cut-offs of ATI for diagnosing hepatic steatosis grades S1, S2, and S3 were 0.91 (0.66 dB/cm/MHz), 0.80 (0.79 dB/cm/MHz), and 0.88 (0.86 dB/cm/MHz), respectively. A subgroup analysis of 86 patients with metabolic dysfunction-associated steatotic liver disease also demonstrated good performance for 2D-SWE and ATI. CONCLUSION 2D-SWE and ATI performed comparably with conventional VCTE and CAP in evaluating CLD, offering reliable alternatives for diagnosing liver fibrosis and steatosis.
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Affiliation(s)
- Tamaki Kobayashi
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
| | - Masaya Sato
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Yoko Soroida
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Hiromi Hikita
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Hiroaki Gotoh
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Tomomi Iwai
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
| | - Makoto Kurano
- Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan
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Park HJ, Kang HJ, Kim SY, Yoon S, Baek S, Song IH, Jang HJ, Jang JK. Effects of hepatic fibrosis on the quantification of hepatic steatosis using the controlled attenuation parameter in patients with chronic hepatitis B. Ultrasonography 2025; 44:83-91. [PMID: 39604096 PMCID: PMC11717679 DOI: 10.14366/usg.24138] [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: 07/16/2024] [Revised: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 11/29/2024] Open
Abstract
PURPOSE This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB). METHODS CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses. RESULTS Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not. CONCLUSION CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.
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Affiliation(s)
- Hee Jun Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyo Jeong Kang
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seonghun Yoon
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seunghee Baek
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Hye Song
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyeon Ji Jang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Righetti R, Cinque F, Patel K, Sebastiani G. The role of noninvasive biomarkers for monitoring cell injury in advanced liver fibrosis. Expert Rev Gastroenterol Hepatol 2025; 19:65-80. [PMID: 39772945 DOI: 10.1080/17474124.2025.2450717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/04/2025] [Indexed: 01/11/2025]
Abstract
INTRODUCTION Accurate and reliable diagnosis and monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) and expanding antifibrotic therapeutic options targeting reversibility of early-stage cirrhosis. This highlights the need to develop more refined and effective noninvasive techniques for the dynamic assessment of fibrogenesis and fibrolysis. AREAS COVERED We conducted a literature review on PubMed, from 1 December 1970, to 1 November 2024, to evaluate and compare available blood-based and imaging-based noninvasive tools for hepatic fibrosis diagnosis and monitoring. Simple scores such as FIB-4 and NAFLD fibrosis score are suitable for excluding significant or advanced fibrosis, while tertiary centers should adopt complex scores and liver stiffness measurement as part of a secondary diagnostic and more comprehensive evaluation. Moreover, the advent of multiomics for high-resolution molecular profiling, and integration of artificial intelligence for noninvasive diagnostics holds promise for revolutionizing fibrosis monitoring and treatment through novel biomarker discovery and predictive omics-based algorithms. EXPERT OPINION The increased shift toward noninvasive diagnostics for liver fibrosis needs to align with personalized medicine, enabling more effective, tailored management strategies for patients with liver disease in the future.
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Affiliation(s)
- Riccardo Righetti
- Chronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Canada
- Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Felice Cinque
- Chronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada
- SC Medicina Indirizzo Metabolico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
- Department of Pathophysiology, Transplantation University of Milan, Milan, Italy
| | - Keyur Patel
- University Health Network Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Canada
| | - Giada Sebastiani
- Chronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Canada
- Division of Gastroenterology and Hepatology, Department of Medicine, McGill University Health Centre, Montreal, Canada
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Gaspar R, Mota J, Almeida MJ, Silva M, Macedo G. The Role of Liver Stiffness Measurement and Spleen Stiffness Measurement in Predicting the Risk of Developing HCC. Diagnostics (Basel) 2024; 14:2867. [PMID: 39767229 PMCID: PMC11675116 DOI: 10.3390/diagnostics14242867] [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: 11/19/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/OBJECTIVES Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer worldwide. More than 90% of cases occur in cirrhotic patients, with the degree of fibrosis being the main risk factor for the development of HCC. Liver biopsy is the gold-standard for fibrosis assessment, but it is an invasive procedure. Liver stiffness measurement (LSM) has shown high accuracy for diagnosing liver cirrhosis, as well as for predicting decompensation and HCC development. More recently, spleen stiffness measurement (SSM) has presented excellent results for ruling in/out high-risk varices and the presence of clinical significant portal hypertension. The aim of our study was to evaluate the relationship between LSM and SSM and the risk of hepatocellular carcinoma. METHODS A prospective study on cirrhotic patients was performed in a tertiary center from January 2020 to May 2024. All patients were submitted to liver and spleen elastography (with a new probe of 100 Hz) by the same blinded operator and were treated in the same institution for the development of hepatocellular carcinoma. RESULTS We included 299 cirrhotic patients, 75.9% male, with a mean age of 61.8 years (±10.0). The median value of LSM was 25.7 kPa [4.5-75.0] and that of SSM was 44.6 kPa [7.9-100.0]. The median follow-up time was 505 days [114.0-1541.0]. During this period, 18 patients developed HCC, with a median time to HCC diagnosis after LSM and SSM of 321 days [63.0-1227.0]. LSM was the only factor associated with the development of HCC (p = 0.002) with an AUC of 0.715. On the other hand, SSM was not associated with the development of HCC. CONCLUSIONS We found that the risk of developing HCC is associated with liver fibrosis but not with portal hypertension (assessed using SSM).
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Affiliation(s)
- Rui Gaspar
- Gastroenterology and Hepatology, Centro Hospitalar de São João, 4200 Porto, Portugal; (J.M.); (M.J.A.); (M.S.); (G.M.)
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11
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Heilani MW, Bolender M, Mücke VT, Schwarzkopf KM, Kubesch-Grün A, Abedin N, Dultz G, Zeuzem S, Welsch C, Friedrich-Rust M, Bojunga J, Herrmann E, Mücke MM. Two-Dimensional and Point Shear-Wave Elastography to Predict Esophageal Varices and Clinically Significant Portal Hypertension in Patients with Chronic Liver Disease. J Clin Med 2024; 13:7719. [PMID: 39768641 PMCID: PMC11676802 DOI: 10.3390/jcm13247719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 11/28/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of our study was to evaluate two-dimensional (2D) and point (p) SWE to predict the presence of esophageal varices (EV) or clinically significant portal hypertension (CSPH). Methods: This was a retrospective analysis of a prospectively performed cohort study of patients with CLD treated in the outpatient clinic of the Frankfurt University Hospital. PSWE using the Hitachi HI Vision ASCENDUS system and the Siemens ACUSON S2000TM system or 2D-SWE using the Toshiba APLIO500 system were analyzed at baseline and during follow-up to predict EV or surrogate parameters of CSPH. ROC curves were calculated for pooled liver stiffness measurements (LSMs) using a bootstrap approach. A combined model of SWE and platelet count was created and a mixed-effect logistic regression analysis using log-transformed values was performed. Results: Overall, 511 patients with CLD and 919 consecutive LSMs were included and 315 patients (61.6%) had signs of CSPH. 2D-SWE performed best to predict EV and CSPH, and the addition of platelet count to the predictive model significantly increased test results for EV (AUC 0.83, 95%-CI: 0.76-0.89; difference in AUC 0.11, 95%-CI: 0.03-0.19, p = 0.004), but only marginally for CSPH (AUC 0.75, 95%-CI: 0.64-0.85; difference in AUC 0.06, 95%-CI: 0.02-0.14, p = 0.150). LSM > 18.5 and >20 kPa were indicative of CSPH and EV, while LSM < 10 kPa and <11 kPa ruled out CSPH and EV, respectively. Conclusions: Our study found that 2D-SWE in combination with platelet count performed best (in comparison to the other SWE methods) to predict EV or CSPH in patients with CLD. Future prospective trials are needed to validate our results.
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Affiliation(s)
- Myriam W. Heilani
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Max Bolender
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Victoria T. Mücke
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Katharina M. Schwarzkopf
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Alica Kubesch-Grün
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Nada Abedin
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Georg Dultz
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Stefan Zeuzem
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Christoph Welsch
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Mireen Friedrich-Rust
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Jörg Bojunga
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
| | - Eva Herrmann
- Institute of Biostatistics and Mathematical Modeling, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany;
| | - Marcus M. Mücke
- Medical Clinic 1, University Hospital, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany; (M.W.H.); (M.B.); (V.T.M.); (K.M.S.); (A.K.-G.); (N.A.); (G.D.); (S.Z.); (C.W.); (M.F.-R.); (J.B.)
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Pachisia AV, Agarwal A, Mehta S, Kumari A, Dwarakanathan V, Sharma S, Kumar S, Mehra L, Dutta R, Das P, Agarwal S, Shalimar, Ahuja V, Makharia GK. Celiac Disease Is Common in Adults With Cryptogenic Cirrhosis and Responds Favorably to Gluten-Free Diet. Am J Gastroenterol 2024. [DOI: 10.14309/ajg.0000000000003244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/07/2024] [Indexed: 01/11/2025]
Abstract
INTRODUCTION:
Liver involvement is common in celiac disease (CeD), and up to 4.6% of patients with cryptogenic cirrhosis have CeD. We investigated the prevalence of CeD in patients with cryptogenic cirrhosis and assessed liver-related outcomes in them on GFD when compared with a propensity score–matched cohort of patients with cryptogenic cirrhosis without CeD.
METHODS:
Consecutive patients with cryptogenic cirrhosis were screened for CeD using IgA anti–tissue transglutaminase antibody (anti-tTG) followed by antiendomysial antibody and duodenal and liver biopsies, on which IgA/anti-tTG colocalization studies were performed. These patients and a cohort of patients with cryptogenic cirrhosis without CeD (1:4 CeD: no CeD matched using propensity score matched for age, sex, Child–Turcotte–Pugh [CTP] and model for end-stage liver disease [MELD]) were initiated on GFD plus standard of care and standard of care, respectively, and followed up for liver-related outcomes for 1 year.
RESULTS:
Of 232 patients with cryptogenic cirrhosis, 14 had high anti-tTG Ab (16.9 ± 10.5 fold rise), with 9 antiendomysial antibody–positive and 11 (4.7%) biopsy-proven CeD. IgA/anti-tTG Ab colocalization was demonstrated in 7/8 liver and 10/11 duodenal biopsies. Patients with cryptogenic cirrhosis with definite CeD (n = 11) and matched cohort without CeD (n = 44) were similar at baseline (age: 31.3 ± 7.7 vs 31.8 ± 9.3 years; 5 [45.5%] vs 15 [34.1%] females; MELDNa 9 [interquartile-range: 8–15.5] vs 12 [9–15]; CTP 7 [6–7.5] vs 6 [5.75–7]). Patients with CeD on GFD improved significantly on follow-up compared with those without CeD (follow-up MELDNa: 9 [7.5–10.5] vs 18.5 [12-20]; P = 0.001 and follow-up CTP: 5 [5-5] vs 8 [7–9]; P < 0.001) with less frequent further decompensations and similar mortality (9.1% vs 18.2%; P = 0.67).
DISCUSSION:
Approximately 4.7% of patients with cryptogenic cirrhosis have biopsy-proven CeD, and their liver-related outcomes improve with GFD.
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Affiliation(s)
| | - Ankit Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Shubham Mehta
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Alka Kumari
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vignesh Dwarakanathan
- Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Sonu Sharma
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sambuddha Kumar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Lalita Mehra
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Rimlee Dutta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Samagra Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Govind K. Makharia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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Sarkar Das T, Meng X, Abdallah M, Bilal M, Sarwar R, Shaukat A. An Assessment of the Feasibility, Patient Acceptance, and Performance of Point-of-Care Transient Elastography for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2024; 14:2478. [PMID: 39594144 PMCID: PMC11592655 DOI: 10.3390/diagnostics14222478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 10/12/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024] Open
Abstract
Background: Vibration-Controlled Transient Elastography (VCTE) with FibroScan is a non-invasive, reliable diagnostic tool for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD), enabling early detection and management to prevent severe liver diseases. VCTE's ease and portability suit primary care, streamlining referrals, promoting lifestyle changes, reducing costs, and benefiting underserved communities. Methods: Studies on point-of-care VCTE were systematically reviewed, followed by meta-analysis using a random-effects model. Pooled proportions with 95% confidence intervals were reported, and heterogeneity was assessed using I2%. Results: A total of twenty studies from 14 countries, including 6159 patients, were analyzed, with three studies from France, two from the U.S., and four from China. The population had a slight male preponderance, with a mean age range of 35-73 years and a BMI range of 24.4-41.1%. The diagnostic accuracy for detecting any fibrosis (≥F1) was reported in four studies (n = 210) with an AUC of 0.74, sensitivity of 69.5%, and specificity of 70.6%. For significant fibrosis (≥F2), eight studies (n = 650) reported an AUC of 0.69, sensitivity of 81.7%, and specificity of 64.6%. Advanced fibrosis (≥F3) was evaluated in 10 studies (n = 619), with an AUC of 0.84, sensitivity of 88.1%, and specificity of 63.8%. Cirrhosis (F4) was assessed in nine studies (n = 533), with an AUC of 0.65, sensitivity of 87.5%, and specificity of 62.6%. Steatosis diagnoses across stages S1 to S3 showed increasing diagnostic accuracies, with AUCs of 0.85, 0.76, and 0.80, respectively. Probe type and BMI were significant covariates influencing diagnostic performance for both fibrosis and steatosis, while the percentage of male participants also showed significant associations. Conclusions: VCTE shows high diagnostic accuracy for fibrosis and steatosis in MASLD patients at the point of care. Future research should assess its implementation in fibroscan settings.
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Affiliation(s)
- Taranika Sarkar Das
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
| | - Xucong Meng
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
| | - Mohamed Abdallah
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Mohammad Bilal
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Raiya Sarwar
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
| | - Aasma Shaukat
- Department of Gastroenterology and Hepatology, New York University, New York, NY 10012, USA; (X.M.)
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Jusufi AH, Trajkovska M. Correlation Between Real-Time Shear Wave Elastography and Liver Serum Markers in Determining the Stage of Liver Fibrosis in Patients with Chronic Liver Diseases. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2024; 45:85-106. [PMID: 39667001 DOI: 10.2478/prilozi-2024-0026] [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] [Indexed: 12/14/2024]
Abstract
Introduction: Non-invasive methods aim to predict the stage of liver fibrosis in line with histological findings via biopsy. Shear wave elastography and serum markers are proven as accurate non-invasive methods for determining liver fibrosis as a modern non-invasive methods compared to liver biopsy in staging hepatic fibrosis. Aims: This study aims to determine the correlation between Shear Wave Elastography and indirect and direct serum markers of fibrosis when staging liver fibrosis. Material and methods: The study was conducted in the Clinic of Gastroenterohepatology, the Institute of Immunology and Human Genetics, and the Institute of Pathology between 2021 and 2023. The study comprises 70 patients with liver lesions, diagnosed based on clinical results, laboratory tests, and ultra-sound imaging. All patients underwent liver biopsy, classified according to Ishak and Metavir score as a reference method for diagnosing liver fibrosis. Real-time shear wave elastography was also performed as a non-invasive method and serum markers were checked for liver fibrosis. Findings: The statistical analysis indicated a positive correlation between the values of direct and indirect liver fibrosis markers and Shear Wave Elastography results. Conclusion: Our study has demonstrated that shear wave elastography has a significant positive correlation with biochemical markers of liver lesions and serum markers of liver fibrosis, whereas it has a negative correlation with platelets.
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Affiliation(s)
- Arzana Hasani Jusufi
- Clinic of Gastroenterohepatology, Ss. Cyril and Methodius University of Skopje, Republic of North Macedonia
| | - Meri Trajkovska
- Clinic of Gastroenterohepatology, Ss. Cyril and Methodius University of Skopje, Republic of North Macedonia
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15
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Huang ZH, Deng MQ, Lin Y, Ye CH, Zheng MH, Zheng YP. Body posture can modulate liver stiffness measured by transient elastography: a prospective observational study. BMC Gastroenterol 2024; 24:386. [PMID: 39482593 PMCID: PMC11526721 DOI: 10.1186/s12876-024-03473-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 10/21/2024] [Indexed: 11/03/2024] Open
Abstract
BACKGROUND Non-invasive measurement of liver stiffness (LS), traditionally performed in the supine position, has been established to assess liver fibrosis. However, fibrosis degree is not the sole determinant of LS, necessitating the identification of relevant confounders. One often-overlooked factor is body posture, and it remains unclear whether normal daily postures interfere with LS irrespective of fibrosis. A prospective two-group comparison study was conducted to investigate the relationship between posture and LS. METHODS Sixty-two adults participated, divided into two groups: patients with chronic liver disease and healthy controls. Both groups were assessed using transient elastography (TE) under the supine, seated, and standing postures. Randomization was applied to the order of the two upright postures. A two-way mixed ANOVA was conducted to assess the posture-dependence of LS and its variations between two groups. RESULTS Results showed that posture differentially affected LS depending on the presence of liver fibrosis. In 31 healthy individuals (baseline LS range: 3.5-6.8 kPa), a transition from the supine (5.0 ± 1.0 kPa) to seated (5.7 ± 1.4 kPa; p = 0.036) or standing (6.2 ± 1.7 kPa; p = 0.002) positions increased LS, indicating liver stiffening. Conversely, in 31 patients with varying fibrosis stages (baseline LS range: 8.8-38.2 kPa), posture decreased LS from the supine (15.9 ± 7.3 kPa) to seated (13.8 ± 6.2 kPa; p < 0.001) or standing (13.9 ± 6.2 kPa; p = 0.001) positions. No significant difference in LS was observed between the seated and standing positions in both groups (control group: 5.7 vs. 6.2 kPa, p = 0.305; patient group: 13.8 vs. 13.9 kPa, p = 1). Additionally, different postures did not elicit significant changes in the success rate (supine, 98.6 ± 4%; seated, 97.6 ± 6%; standing, 99.1 ± 3%; p = 0.258) and IQR/median value (supine, 25 ± 8%; seated, 29 ± 15%; standing, 29 ± 12%; p = 0.117), implying no impact on both measurement feasibility and reliability. CONCLUSIONS We demonstrated, for the first time, the feasibility of utilizing upright postures as an alternative measurement protocol for TE. We further unravel a previously unrecognized role of transitioning between different postures to assist the diagnosis of cirrhosis. The findings suggested that daily physiological activity of postural changes suffices to alter LS. Therefore, body positioning should be standardized and carefully considered when interpreting LS.
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Affiliation(s)
- Zi-Hao Huang
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China
| | - Miao-Qin Deng
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China
| | - Yangmin Lin
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China
| | - Chen-Hui Ye
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Yong-Ping Zheng
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
- Research Institute for Smart Ageing, The Hong Kong Polytechnic University, Hong Kong, China.
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Salama M, Darwesh N, Elsabaawy MM, Abdelsameea E, Gomaa A, Sabry A. Long-Term Outcomes of Patients with Liver Cirrhosis After Eradication of Chronic Hepatitis C with Direct-Acting Antiviral Drugs (DAAs). J Hepatocell Carcinoma 2024; 11:2115-2132. [PMID: 39493267 PMCID: PMC11531736 DOI: 10.2147/jhc.s475810] [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: 06/02/2024] [Accepted: 10/15/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose This research was designed to determine the long-term outcomes in patients with liver cirrhosis who achieved sustained virological response (SVR) after direct-acting anti-viral drugs (DAAs) based regimens. Patients and Methods This study involved 193 patients with HCV-related cirrhosis who had previously completed DAAs regimens and accomplished SVR. Clinical, laboratory, and radiological features at the first and 3rd-year follow-up after the end of treatment were analyzed. Overall survival (OS) and incidence of liver decompensation or hepatocellular carcinoma (HCC) were determined at the 5-year follow-up. Results About 68.4% of our patients with HCV-related cirrhosis were males and their mean age was 54.8 ± 7.7 years. Follow-up at the first and the 3rd-year showed significant improvements in albumin (P = 0.001), liver enzymes (P = 0.001), alpha-fetoprotein (AFP) (P < 0.001), platelet count (P = 0.001), the model for end-stage liver disease (MELD) score (P = 0.001 and 0.01), FIB4 and Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores (p < 0.001). The liver stiffness (LS) also significantly improved (p = 0.001). At the 5th year, the mean OS was 58.3 months, with 14.5% and 17.6% of patients developing de-novo HCC and decompensation, respectively. The mean OS at the 5th-year follow-up was shorter in patients who developed HCC and those with liver decompensation (p = 0.001). Alfa-fetoprotein and LS are predictive factors for HCC development. Conclusion Despite achieving SVR, continuous surveillance for HCC and new-onset decompensation is mandatory in patients with liver cirrhosis.
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Affiliation(s)
- Mohsen Salama
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Nehad Darwesh
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Maha Mohammad Elsabaawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Asmaa Gomaa
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Aliaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
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Huang W, Peng Y, Kang L. Advancements of non‐invasive imaging technologies for the diagnosis and staging of liver fibrosis: Present and future. VIEW 2024; 5. [DOI: 10.1002/viw.20240010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 06/28/2024] [Indexed: 01/04/2025] Open
Abstract
AbstractLiver fibrosis is a reparative response triggered by liver injury. Non‐invasive assessment and staging of liver fibrosis in patients with chronic liver disease are of paramount importance, as treatment strategies and prognoses depend significantly on the degree of fibrosis. Although liver fibrosis has traditionally been staged through invasive liver biopsy, this method is prone to sampling errors, particularly when biopsy sizes are inadequate. Consequently, there is an urgent clinical need for an alternative to biopsy, one that ensures precise, sensitive, and non‐invasive diagnosis and staging of liver fibrosis. Non‐invasive imaging assessments have assumed a pivotal role in clinical practice, enjoying growing popularity and acceptance due to their potential for diagnosing, staging, and monitoring liver fibrosis. In this comprehensive review, we first delved into the current landscape of non‐invasive imaging technologies, assessing their accuracy and the transformative impact they have had on the diagnosis and management of liver fibrosis in both clinical practice and animal models. Additionally, we provided an in‐depth exploration of recent advancements in ultrasound imaging, computed tomography imaging, magnetic resonance imaging, nuclear medicine imaging, radiomics, and artificial intelligence within the field of liver fibrosis research. We summarized the key concepts, advantages, limitations, and diagnostic performance of each technique. Finally, we discussed the challenges associated with clinical implementation and offer our perspective on advancing the field, hoping to provide alternative directions for the future research.
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Affiliation(s)
- Wenpeng Huang
- Department of Nuclear Medicine Peking University First Hospital Beijing China
| | - Yushuo Peng
- Department of Nuclear Medicine Peking University First Hospital Beijing China
| | - Lei Kang
- Department of Nuclear Medicine Peking University First Hospital Beijing China
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Likhitsup A, Chen VL, Fontana RJ. Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults. JAMA Netw Open 2024; 7:e2425822. [PMID: 39102266 PMCID: PMC11301549 DOI: 10.1001/jamanetworkopen.2024.25822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 06/06/2024] [Indexed: 08/06/2024] Open
Abstract
Importance Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown. Objective To assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals. Design, Setting, and Participants This survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024. Exposures Adult NHANES participants enrolled between January 2017 and March 2020. Main Outcomes and Measures Baseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use. Results Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15 584 599 (95% CI, 13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14 036 024 [95% CI, 11 202 460-17 594 452]) and nonsteroidal anti-inflammatory drugs (14 793 837 [95% CI, 13 014 623-16 671 897]). The most common reason for consuming turmeric and green tea was to improve or maintain health. Conclusions and Relevance In this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.
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Affiliation(s)
- Alisa Likhitsup
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Vincent L. Chen
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Robert J. Fontana
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
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Reiberger T, Lens S, Cabibbo G, Nahon P, Zignego AL, Deterding K, Elsharkawy AM, Forns X. EASL position paper on clinical follow-up after HCV cure. J Hepatol 2024; 81:326-344. [PMID: 38845253 DOI: 10.1016/j.jhep.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/05/2024] [Indexed: 07/26/2024]
Abstract
Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.
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Affiliation(s)
- Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy
| | - Pierre Nahon
- AP-HP, Hôpitaux Universitaires Paris Seine Saint-Denis, Liver Unit, Bobigny; Université Sorbonne Paris Nord, F-93000 Bobigny; Inserm, UMR-1138 "Functional Genomics of Solid Tumors", Centre de Recherche des Cordeliers, Université de Paris, France
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | - Katja Deterding
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School. Germany
| | - Ahmed M Elsharkawy
- Liver Unit, Queen Elizabeth Hospital Birmingham. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham, United Kingdom
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona. IDIBAPS. Liver and Digestive Diseases Networking Biomedical Research Centre (CIBERehd). University of Barcelona. Spain.
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20
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Wang X, Liu B, Wu C, Huang Z, Zhou Y, Wu X, Zheng Y. Shear wave trajectory detection in ultra-fast M-mode images for liver fibrosis assessment: A deep learning-based line detection approach. ULTRASONICS 2024; 142:107358. [PMID: 38901149 DOI: 10.1016/j.ultras.2024.107358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 04/30/2024] [Accepted: 05/27/2024] [Indexed: 06/22/2024]
Abstract
Stiffness measurement using shear wave propagation velocity has been the most common non-invasive method for liver fibrosis assessment. The velocity is captured through a trace recorded by transient ultrasonographic elastography, with the slope indicating the velocity of the wave. However, due to various factors such as noise and shear wave attenuation, detecting shear wave trajectory on wave propagation maps is a challenging task. In this work, we made the first attempt to use deep learning methods for shear wave trajectory detection on wave propagation maps. Specifically, we adopted five deep learning models in this task and evaluated them by using a well-acknowledged metric based on EA-Angular-Score (EAA) and task-specific metric based on Young s-Score (Ys) in the line-detection field. Furthermore, we proposed an end-to-end framework based on a Transformer and Hough transform, named Transformer-enhanced Hough Transform (TEHT). It took a wave propagation map as input image and directly output the slope of the shear wave trajectory. The framework extracts multi-scale local features from wave propagation maps, employs a deformable attention mechanism for feature fusion, identifies the target line using the Hough transform's voting mechanism, and calculates the contribution of each scale through channel attention. Wave propagation maps from 68 patients were utilized in this study, with manual annotation performed by a rater who was trained as a radiologist, serving as the reference value. The evaluation revealed that the SLNet model exhibited F-measure of EA and Ys values as 40.33 % and 40.72 %, respectively, while the TEHT model showed F-measure of EA and Ys values as 80.96 % and 98.00 %, respectively. TEHT yielded significantly better performance than other deep learning models. Moreover, TEHT demonstrated strong concordance with the gold standard, yielding R2 values of 0.967 and 0.968 for velocity and liver stiffness, respectively. The present study therefore suggests the application of the TEHT model for assessing liver fibrosis owing to its superiority among the five deep learning models.
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Affiliation(s)
- Xinyi Wang
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region
| | - Bo Liu
- Department of Computing, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region
| | - Chonglin Wu
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region
| | - Zihao Huang
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region
| | - Yongjin Zhou
- School of Biomedical Engineering, University of Shenzhen, Shenzhen, China
| | - Xiaoming Wu
- Department of Computing, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region
| | - Yongping Zheng
- Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region; Research Institute for Smart Ageing, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region.
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21
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Nakano M, Kuromatsu R, Kawaguchi T. Ultrasonographic Assessment of Tissue Stiffness: Recent Progress in Transient Elastography and Shear Wave Elastography in the Liver and Various Organs. Kurume Med J 2024; 70:1-10. [PMID: 38763738 DOI: 10.2739/kurumemedj.ms7012010] [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] [Indexed: 05/21/2024]
Abstract
Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two representative techniques are transient elastography (FibroScan®) and shear wave elastography. These modalities are now generally used for the assessment of liver fibrosis, the prediction of hepatocarcinogenesis, and determining prognosis. In addition, shear wave elastography is available, not only for the liver but also for various other organs, including the breast and brain. In the breast and brain, shear wave elastography distinguishes malignant lesions from benign ones. Moreover, shear wave elastography can be useful for differentiating between ischemic and hemorrhagic strokes. This review summarizes the recent progress in transient elastography and shear wave elastography of the liver and introduces the advantages of ultrasonographic assessment of tissue stiffness in various organs, including the breast, brain, kidney, heart, thyroid, pancreas, muscle, and bone.
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Affiliation(s)
- Masahito Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Ryoko Kuromatsu
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
- Ultrasound Diagnostic Center, Kurume University Hospital
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
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22
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Najafi N, Razavi A, Jafarpour H, Raei M, Azizi Z, Davoodi L, Abdollahi A, Frouzanian M. Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results. Ann Med Surg (Lond) 2024; 86:3841-3846. [PMID: 38989210 PMCID: PMC11230742 DOI: 10.1097/ms9.0000000000002095] [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: 11/04/2022] [Accepted: 12/24/2023] [Indexed: 07/12/2024] Open
Abstract
Background Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.
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Affiliation(s)
- Narges Najafi
- Department of Infectious Diseases, School of Medicine, Antimicrobial Resistance Research Center, Communicable Diseases Research Institutes, Qaem Shahr Razi Hospital, Mazandaran University of Medical Sciences
| | - Alireza Razavi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Hamed Jafarpour
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Maedeh Raei
- Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Zahra Azizi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Lotfollah Davoodi
- Department of Infectious Diseases, School of Medicine, Antimicrobial Resistance Research Center, Communicable Diseases Research Institutes, Qaem Shahr Razi Hospital, Mazandaran University of Medical Sciences
| | - Amirsaleh Abdollahi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
| | - Mehran Frouzanian
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences
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23
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Zhou X, Duan H, Li Q, Wang Q, Sun X. Efficacy and safety of potassium-competitive acid inhibitors in the treatment of gastroesophageal reflux: a systematic review and meta-analysis. Scand J Gastroenterol 2024; 59:788-797. [PMID: 38741565 DOI: 10.1080/00365521.2024.2349638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 03/30/2024] [Accepted: 04/24/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD. METHODS We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis. RESULTS Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSIONS Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.
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Affiliation(s)
- Xinxu Zhou
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Hui Duan
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Qian Li
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Qiong Wang
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Xiaobin Sun
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
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24
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Kalil JA, Deschenes M, Perrier H, Zlotnik O, Metrakos P. Navigating Complex Challenges: Preoperative Assessment and Surgical Strategies for Liver Resection in Patients with Fibrosis or Cirrhosis. Biomedicines 2024; 12:1264. [PMID: 38927471 PMCID: PMC11201140 DOI: 10.3390/biomedicines12061264] [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: 04/15/2024] [Revised: 05/28/2024] [Accepted: 06/03/2024] [Indexed: 06/28/2024] Open
Abstract
This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes.
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Affiliation(s)
- Jennifer A. Kalil
- Department of Surgery, Royal Victoria Hospital, McGill University Health Center, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada; (J.A.K.); (H.P.); (O.Z.)
- Cancer Research Program, McGill University Health Center, Research Institute, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada
| | - Marc Deschenes
- Department of Medicine, Division of Gastroenterology & Hepatology & Transplantation, Royal Victoria Hospital, McGill University Health Center, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada;
| | - Hugo Perrier
- Department of Surgery, Royal Victoria Hospital, McGill University Health Center, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada; (J.A.K.); (H.P.); (O.Z.)
| | - Oran Zlotnik
- Department of Surgery, Royal Victoria Hospital, McGill University Health Center, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada; (J.A.K.); (H.P.); (O.Z.)
- Cancer Research Program, McGill University Health Center, Research Institute, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada
| | - Peter Metrakos
- Department of Surgery, Royal Victoria Hospital, McGill University Health Center, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada; (J.A.K.); (H.P.); (O.Z.)
- Cancer Research Program, McGill University Health Center, Research Institute, 1001 Blvd Decarie, Montreal, QC H4A 3J1, Canada
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25
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De Vincentis A, Tavaglione F, Namba S, Kanai M, Okada Y, Kamatani Y, Maurotti S, Pedone C, Antonelli Incalzi R, Valenti L, Romeo S, Vespasiani-Gentilucci U. Poor accuracy and sustainability of the first-step FIB4 EASL pathway for stratifying steatotic liver disease risk in the general population. Aliment Pharmacol Ther 2024; 59:1402-1412. [PMID: 38497224 DOI: 10.1111/apt.17953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/15/2023] [Accepted: 03/03/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND AND AIMS The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes. METHODS We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver-related events occurring within 3 and 10 years (3/10 year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations. RESULTS FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs. CONCLUSIONS The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield.
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Affiliation(s)
- Antonio De Vincentis
- Internal Medicine Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy
| | - Federica Tavaglione
- Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Shinichi Namba
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
| | - Masahiro Kanai
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Yukinori Okada
- Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
- Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
- Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan
- Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan
- Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Japan
| | - Yoichiro Kamatani
- Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
| | - Samantha Maurotti
- Clinical Nutrition Unit, Department of Medical and Surgical Science, Magna Graecia University, Catanzaro, Italy
| | - Claudio Pedone
- Unit of Geriatrics, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy
| | - Raffaele Antonelli Incalzi
- Internal Medicine Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
- Translational Medicine, Biological Resource Center, Department of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Stefano Romeo
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Clinical Nutrition Unit, Department of Medical and Surgical Science, Magna Graecia University, Catanzaro, Italy
- Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Umberto Vespasiani-Gentilucci
- Clinical Medicine and Hepatology Unit, Department of Internal Medicine and Geriatrics, Campus Bio-Medico University, Rome, Italy
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Zheng T, Qu Y, Chen J, Yang J, Yan H, Jiang H, Song B. Noninvasive diagnosis of liver cirrhosis: qualitative and quantitative imaging biomarkers. Abdom Radiol (NY) 2024; 49:2098-2115. [PMID: 38372765 DOI: 10.1007/s00261-024-04225-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/20/2024]
Abstract
A diagnosis of cirrhosis initiates a shift in the management of chronic liver disease and affects the diagnostic workflow and treatment decision of primary liver cancer. Liver biopsy remains the gold standard for cirrhosis diagnosis, but it is invasive and susceptible to sampling bias and observer variability. Various qualitative and quantitative imaging biomarkers based on ultrasound, CT and MRI have been proposed for noninvasive diagnosis of cirrhosis. Qualitative imaging features are easy to apply but have moderate diagnostic sensitivity. Elastography techniques allow quantitative assessment of liver stiffness and are highly accurate for cirrhosis diagnosis. Ultrasound elastography are widely used in clinical practice, while MR elastography has narrower availability. Although not applicable in clinical practice yet, other quantitative imaging features, including liver surface nodularity, linear and volumetric measurement, extracellular volume fraction, liver enhancement on hepatobiliary phase, and parameters derived from diffusion-weighted imaging, can provide additional information of liver morphology, perfusion, and function, thus may increase diagnosis performance. The introduction of radiomics and deep learning has further improved diagnostic accuracy while reducing subjectivity. Several imaging features may also help to assess liver function and outcomes in patients with cirrhosis. In this review, we summarize the qualitative and quantitative imaging biomarkers for noninvasive cirrhosis diagnosis, and the assessment of liver function and outcomes, and discuss the challenges and future directions in this field.
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Affiliation(s)
- Tianying Zheng
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan, Chengdu, Sichuan, China
| | - Yali Qu
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan, Chengdu, Sichuan, China
| | - Jie Chen
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan, Chengdu, Sichuan, China
| | - Jie Yang
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hualin Yan
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan, 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan, Chengdu, Sichuan, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan, 610041, China.
- Functional and Molecular Imaging Key Laboratory of Sichuan, Chengdu, Sichuan, China.
- Department of Radiology, Sanya People's Hospital, Sanya, Hainan, China.
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Cetin T, Tokur O, Bozkurt HB, Aydin S, Memis KB, Kantarci M. Shear Wave Ultrasonographic Elastography in Pediatric Spleens and Its Role in Differential Diagnosis. Diagnostics (Basel) 2024; 14:1142. [PMID: 38893668 PMCID: PMC11171796 DOI: 10.3390/diagnostics14111142] [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: 04/29/2024] [Revised: 05/17/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024] Open
Abstract
Shear wave elastography (SWE) has become popular in clinical practice for many diseases. However, there is not adequate research on spleen-related diseases. This study aimed to investigate the potential of quantitative values obtained through SWE in evaluating spleen pathologies in the pediatric population and to demonstrate its performance to differentiate splenomegaly-related diseases. The research group retrospectively included children with pathological diagnoses related to the spleen from November 2016 to April 2021, and they were categorized into three groups, including portal hypertension (PH), benign lymphoid hyperplasia (BLH), and malignant infiltration (MI). Spleen sizes and parenchymal stiffness were also calculated for each group. Subsequently, mean spleen stiffness in each group was compared with normal values within the same age group. In total, 2781 children (1379 children for the study group; 1402 children for the control group) were enrolled in the study. The highest stiffness was observed in the PH group, which is statistically higher than others (p < 0.05). Although the mean spleen stiffness in the group with BLH was higher than the control and MI group, the difference was not statistically significant (p = 0.08). The mean stiffness in the group with MI was significantly lower than both the control group (p = 0.005) and PH (p = 0.01). In conclusion, using SWE in the differential diagnosis of etiologies causing splenomegaly could make an important contribution.
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Affiliation(s)
- Turkhun Cetin
- Department of Radiology, Erzincan University, Erzincan 24100, Turkey; (T.C.); (S.A.); (K.B.M.); (M.K.)
| | - Oguzhan Tokur
- Department of Radiology, Kutahya Health Sciences University, Kutahya 43020, Turkey
| | | | - Sonay Aydin
- Department of Radiology, Erzincan University, Erzincan 24100, Turkey; (T.C.); (S.A.); (K.B.M.); (M.K.)
| | - Kemal Bugra Memis
- Department of Radiology, Erzincan University, Erzincan 24100, Turkey; (T.C.); (S.A.); (K.B.M.); (M.K.)
| | - Mecit Kantarci
- Department of Radiology, Erzincan University, Erzincan 24100, Turkey; (T.C.); (S.A.); (K.B.M.); (M.K.)
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Fricker GP, Ghany MG, Mera J, Pinsky BA, Ward JW, Chung RT. Tools Needed to Support Same-Day Diagnosis and Treatment of Current Hepatitis C Virus Infection. J Infect Dis 2024; 229:S362-S369. [PMID: 37739799 PMCID: PMC11078313 DOI: 10.1093/infdis/jiad177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/12/2023] [Accepted: 05/16/2023] [Indexed: 09/24/2023] Open
Abstract
The current multiday diagnosis and treatment paradigm for hepatitis C virus (HCV) infection results in far fewer patients receiving treatment with direct-acting antiviral agents than those with diagnosed HCV infection. To achieve HCV elimination, a paradigm shift in access to HCV treatment is needed from multiday testing and treatment algorithms to same-day diagnosis and treatment. This shift will require new tools, such as point-of-care (POC) antigen tests or nucleic acid tests for HCV and hepatitis B virus (HBV) and nucleic acid tests for human immunodeficiency virus (HIV) that do not require venous blood. This shift will also require better use of existing resources, including expanded access to HCV treatment and available POC tests, novel monitoring approaches, and removal of barriers to approval. A same-day diagnosis and treatment paradigm will substantially contribute to HCV elimination by improving HCV treatment rates and expanding access to treatment in settings where patients have brief encounters with healthcare.
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Affiliation(s)
- Gregory P Fricker
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Marc G Ghany
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Jorge Mera
- Infectious Diseases, Cherokee Nation Health Services, Tahlequah, Oklahoma, USA
- Department of Medicine, Division of Infectious Diseases, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Benjamin A Pinsky
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, University School of Medicine, Stanford, CaliforniaUSA
| | - John W Ward
- Coalition for Global Hepatitis Elimination, The Task Force for Global Health, Atlanta, Georgia, USA
| | - Raymond T Chung
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
- Hepatology and Liver Center, Massachusetts General Hospital, Boston, Massachusetts, USA
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Schrecker C, Schulze F, Trojan J, Bechstein WO, Zeuzem S, Koch C. Diagnostic performance of non-invasive liver fibrosis scores in patients with early-intermediate hepatocellular carcinoma. J Cancer Res Clin Oncol 2024; 150:187. [PMID: 38602548 PMCID: PMC11008064 DOI: 10.1007/s00432-024-05708-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 03/16/2024] [Indexed: 04/12/2024]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) arises in individuals with underlying liver disease. Diagnosing the degree of hepatic fibrosis helps to determine the severity of the underlying liver disease and may influence therapeutic decisions in HCC patients. Non-invasive fibrosis scores can be used to estimate the degree of fibrosis in liver disease patients, but most of these scores were developed in patients with viral hepatitis and without HCC. This study explored the ability of the Fibrosis-4 Index (FIB-4), the AST/Platelet Ratio Index (APRI), and the AST/ALT ratio to diagnose or exclude advanced fibrosis (METAVIR F3/4 versus F0-2) in patients with early-intermediate, potentially resectable HCC. METHODS We retrospectively reviewed 119 patients who underwent hepatic resection for HCC at a tertiary centre (2007-2019), 75 of whom had advanced fibrosis (prevalence 63%). Histological assessment of the surgical liver specimen was used as a reference standard for the degree of fibrosis. RESULTS Overall diagnostic performance was highest for the FIB-4 Index, with an area under the receiver operating characteristic curve (AUROC) of 0.82, compared with 0.78 for APRI, and 0.56 for the AST/ALT ratio. Using established cut-off values, FIB-4 achieved a 90% positive predictive value at the higher cut-off (3.25) and a 90% negative predictive value at the lower cut-off (1.45). CONCLUSION The FIB-4 Index could reliably diagnose or exclude advanced fibrosis in patients with early-intermediate HCC, and may thus have a role in guiding therapeutic decisions in these patients.
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Affiliation(s)
- Christopher Schrecker
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
| | - Falko Schulze
- Dr. Senckenberg Institute of Pathology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Jörg Trojan
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Wolf Otto Bechstein
- Department of Surgery, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Stefan Zeuzem
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Christine Koch
- Department of Medicine, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
- Frankfurt Institute of Clinical Cancer Research, Krankenhaus Nordwest, Frankfurt am Main, Germany.
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Lai JCT, Liang LY, Wong GLH. Noninvasive tests for liver fibrosis in 2024: are there different scales for different diseases? Gastroenterol Rep (Oxf) 2024; 12:goae024. [PMID: 38605932 PMCID: PMC11009030 DOI: 10.1093/gastro/goae024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/25/2024] [Accepted: 03/11/2024] [Indexed: 04/13/2024] Open
Abstract
Liver fibrosis is the common pathway from various chronic liver diseases and its progression leads to cirrhosis which carries a significant risk for the development of portal hypertension-related complications and hepatocellular carcinoma. It is crucial to identify and halt the worsening of liver fibrosis given its important prognostic implication. Liver biopsy is the gold standard for assessing the degree of liver fibrosis but is limited due to its invasiveness and impracticality for serial monitoring. Many noninvasive tests have been developed over the years trying to assess liver fibrosis in a practical and accurate way. The tests are mainly laboratory- or imaging-based, or in combination. Laboratory-based tests can be derived from simply routine blood tests to patented laboratory parameters. Imaging modalities include ultrasound and magnetic resonance elastography, in which vibration-controlled transient elastography is the most widely validated and adopted whereas magnetic resonance elastography has been proven the most accurate liver fibrosis assessment tool. Nonetheless, noninvasive tests do not always apply to all liver diseases, nor does a common cut-off value of a test mean the same degree of liver fibrosis in different scenarios. In this review, we discuss the diagnostic and prognostic performance, as well as the confounders and limitations, of different noninvasive tests on liver fibrosis assessment in various liver diseases.
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Affiliation(s)
- Jimmy Che-To Lai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lilian Yan Liang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
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Behari J. Spleen Stiffness Measurement in Metabolic Dysfunction-Associated Steatotic Liver Disease-Value Added or Work in Progress? Dig Dis Sci 2024; 69:1093-1095. [PMID: 38332210 DOI: 10.1007/s10620-024-08270-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 01/02/2024] [Indexed: 02/10/2024]
Affiliation(s)
- Jaideep Behari
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, 3471 Fifth Avenue, Kaufmann Medical Building Suite 201, Pittsburgh, PA, 15213, USA.
- Thomas E. Starzl Transplantation Institute at UPMC, Pittsburgh, PA, 15213, USA.
- Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
- Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, 15232, USA.
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Peltec A, Sporea I. Multiparametric ultrasound as a new concept of assessment of liver tissue damage. World J Gastroenterol 2024; 30:1663-1669. [PMID: 38617743 PMCID: PMC11008374 DOI: 10.3748/wjg.v30.i12.1663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/05/2024] [Accepted: 03/12/2024] [Indexed: 03/28/2024] Open
Abstract
Liver disease accounts for approximately 2 million deaths per year worldwide. All chronic liver diseases (CLDs), whether of toxic, genetic, autoimmune, or infectious origin, undergo typical histological changes in the structure of the tissue. These changes may include the accumulation of extracellular matrix material, fats, triglycerides, or tissue scarring. Noninvasive methods for diagnosing CLD, such as conventional B-mode ultrasound (US), play a significant role in diagnosis. Doppler US, when coupled with B-mode US, can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation. US elastography can assess liver stiffness, serving as a surrogate marker for liver fibrosis. It is important to note that interpreting these values should not rely solely on a histological classification. Contrast-enhanced US (CEUS) provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions. Clinical evaluation, the etiology of liver disease, and the patient current comorbidities all influence the interpretation of liver stiffness measurements. These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD. B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis. The controlled attenuation parameter requires a dedicated device, and cutoff values are not clearly defined. Quan-titative US parameters for liver fat estimation include the attenuation coefficient, backscatter coefficient, and speed of sound. These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters. Multiparametric US (MPUS) of the liver introduces a new concept for complete noninvasive diagnosis. It encourages examiners to utilize the latest features of an US machine, including conventional B-mode, liver stiffness evaluation, fat quantification, dispersion imaging, Doppler US, and CEUS for focal liver lesion characterization. This comprehensive approach allows for diagnosis in a single examination, providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal. MPUS, in the hands of skilled clinicians, becomes an invaluable predictive tool for diagnosing, staging, and monitoring CLD.
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Affiliation(s)
- Angela Peltec
- Department of Internal Medicine, Discipline of Gastroenterology, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chishinev 2019, Moldova
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, "Victor Babes" University of Medicine and Pharmacy, Timisoara 300736, Romania
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Atzori SM, Pasha Y, Maurice JB, Taylor-Robinson SD, Campbell L, Lim AKP. Prospective evaluation of liver shearwave elastography measurements with 3 different technologies and same day liver biopsy in patients with chronic liver disease. Dig Liver Dis 2024; 56:484-494. [PMID: 37968144 DOI: 10.1016/j.dld.2023.10.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 08/26/2023] [Accepted: 10/25/2023] [Indexed: 11/17/2023]
Abstract
BACKGROUND Most ultrasound-based methods for assessing liver fibrosis still need further validation with liver biopsy used as gold standard to assess their accuracy. AIMS To assess accuracy of three shear wave elastography (SWE) methods: 1) Philips Elast Point Quantification (ElastPQTM), 2) Siemens Virtual TouchTM Quantification (VTQ) acoustic radiation force impulse (ARFI), and 3) transient elastography (TE) measured by Echosens FibroscanTM. METHODS 160 patients underwent liver stiffness measurements (LSM) with three SWE methods immediately prior to liver biopsy. RESULTS The number of LSM required for reliable studies could be reduced to 6 for ElastPQ and to 7 for VTQ from standard recommendations of 10. Significant fibrosis and interquartile range/median (IQR/M)> 30 were independent predictors for lower reliability for detection of liver fibrosis. Ordinal logistic regression corrected for age showed that there was a significant interaction between steatosis (p = 0.008) and lobular inflammation (p = 0.04) and VTQ (ARFI) and between lobular inflammation and TE (p = 0.006). CONCLUSIONS We showed variations in SWE measurements using different ARFI technologies. TE and ElastPQ achieved good diagnostic performance, whereas VTQ showed lower diagnostic accuracy. The number of measurements required for reliable studies can be reduced to 6 for ElastPQ and to 7 for VTQ, which have important clinical implications.
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Affiliation(s)
- Sebastiana M Atzori
- Liver Unit QEQM Wing St. Mary Hospital, Department of Surgery and Cancer, Imperial College London, South Wharf Road, London W1 1NY, United Kingdom; Department of Medicine, Sassari University Hospital, Via Enrico de Nicola, Sassari 07100, Italy.
| | - Yasmin Pasha
- Liver Unit QEQM Wing St. Mary Hospital, Department of Surgery and Cancer, Imperial College London, South Wharf Road, London W1 1NY, United Kingdom
| | - James B Maurice
- Liver Unit QEQM Wing St. Mary Hospital, Department of Surgery and Cancer, Imperial College London, South Wharf Road, London W1 1NY, United Kingdom; UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, London, Rowland Hill Street, NW3 2QG, United Kingdom
| | - Simon D Taylor-Robinson
- Liver Unit QEQM Wing St. Mary Hospital, Department of Surgery and Cancer, Imperial College London, South Wharf Road, London W1 1NY, United Kingdom
| | - Louise Campbell
- Liver Unit QEQM Wing St. Mary Hospital, Department of Surgery and Cancer, Imperial College London, South Wharf Road, London W1 1NY, United Kingdom; Office of the Clinical Director, Tawazun Health, 23 Harley Street, London W1G 9QN, United Kingdom
| | - Adrian K P Lim
- Imaging Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, United Kingdom
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Atabieke F, Li XJ, Aierken A, Li J, Zhang Y, Aizezi Y, Gao HL, Zhang ZQ. Association between frailty and hepatic fibrosis in NAFLD among middle-aged and older adults: results from NHANES 2017-2020. Front Public Health 2024; 12:1330221. [PMID: 38389936 PMCID: PMC10883311 DOI: 10.3389/fpubh.2024.1330221] [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: 10/30/2023] [Accepted: 01/29/2024] [Indexed: 02/24/2024] Open
Abstract
Background Although previous studies found that frailty is prevalent in NAFLD patients with advanced liver fibrosis and cirrhosis, studies examining the relationship are spare. Aim Our study aspires to investigate the potential correlation between the Frailty Index (FI) and hepatic fibrosis among middle-aged and older adults with NAFLD. Methods Data from the 2017-2020.03 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 2,383 participants aged 50 years and older included. The quantification of frailty was executed employing a 49-item frailty index. The recognition of hepatic steatosis and fibrosis was accomplished through the utilization of the controlling attenuation parameter (CAP) and transient elastography (TE). The relationship between the FI and hepatic fibrosis were investigated employing univariable and multivariable-adjusted logistic regression analyses. A subgroup analysis was conducted, dividing the subjects based on gender, Body Mass Index (BMI), and the presence of hyperlipidemia. Results The findings demonstrated a positive correlation between the FI and significant hepatic fibrosis in NAFLD, even after using multivariate logistic regression models adjusting for potential confounding factors (OR = 1.022, 95% CI, 1.004-1.041) and in tertiles (Q3vs Q1: OR = 2.004, 95% CI, 1.162-3.455). In the subgroup analysis, the correlation was more statistically significant in male (OR = 1.046, 95% CI, 1.022-1.071), under/normal weight (OR = 1.077, 95% CI, 1.009-1.150), overweight (OR = 1.040, 95% CI, 1.010-1.071), and subjects without hyperlipidemia (OR = 1.054, 95% CI, 1.012-1.097). The area under the Receiver Operating Characteristic (ROC) curve for the FI in assessing the existence of substantial fibrosis in NAFLD was 0.612 (95% CI, 0.596-0.628). Conclusion This study demonstrated a positive correlation between significant hepatic fibrosis and frailty, particularly among males aged 50 years and older, who were non-obese and did not have hyperlipidemia with NAFLD. Additional studies are required to further validate these findings.
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Affiliation(s)
- Falide Atabieke
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Xiu-Juan Li
- Department of Pathophysiology, School of Basic Medical Sciences Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Ailikamu Aierken
- Xinjiang Medical University School of Clinical Medicine, Children's Hospital of the Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Jian Li
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yu Zhang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yierzhati Aizezi
- Center of Critical Care Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Hong-Liang Gao
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Zhi-Qiang Zhang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
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Kalwa PL, Walz S, Granai M, Fend F, Stenzl A, Schäffer TE. Differentiation of bladder cancer with water flow elastography (WaFE). J Mech Behav Biomed Mater 2024; 150:106319. [PMID: 38142569 DOI: 10.1016/j.jmbbm.2023.106319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/04/2023] [Accepted: 12/10/2023] [Indexed: 12/26/2023]
Abstract
Cancer affects the mechanical properties of tissue. Therefore, elastography techniques can be used to differentiate cancerous from healthy tissue. Due to probe size and restricted handling, most elastography techniques are not applicable in minimally invasive surgery (MIS). Established techniques such as endoscopic ultrasound elastography measure under undefined boundary conditions, making the determination of quantitative mechanical properties challenging. Water flow elastography (WaFE) has recently been introduced for application in MIS. Here, we present an improved WaFE measurement method in which the probe attaches itself to the sample with a small suction pressure. This leads to defined boundary conditions, allowing for a quantitative determination of the Young's modulus of tissue. To facilitate fast measurements, we developed a correction model for the hydrodynamic resistance and the fluid inertia of the tubing. We used WaFE for ex vivo measurements on human bladders and found a significantly larger Young's modulus for cancerous vs. healthy tissue. We determined the optimal classification threshold for the Young's modulus to be 8 kPa and found that WaFE can differentiate between cancerous and healthy tissue with a sensitivity of 0.96 and a specificity of 1. Our results underline that WaFE can be a helpful differentiating tool in MIS.
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Affiliation(s)
- Paul L Kalwa
- Institute of Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany
| | - Simon Walz
- Department of Urology, University of Tübingen Medical Center, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
| | - Massimo Granai
- Institute of Pathology and Neuropathology, University Hospital of Tübingen, Liebermeisterstr. 8, 72076 Tübingen, Germany
| | - Falko Fend
- Institute of Pathology and Neuropathology, University Hospital of Tübingen, Liebermeisterstr. 8, 72076 Tübingen, Germany
| | - Arnulf Stenzl
- Department of Urology, University of Tübingen Medical Center, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
| | - Tilman E Schäffer
- Institute of Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
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Hildenbrand FF, Illi B, von Felten S, Bachofner J, Gawinecka J, von Eckardstein A, Müllhaupt B, Mertens JC, Blümel S. Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis. BMC Gastroenterol 2024; 24:54. [PMID: 38291388 PMCID: PMC10825988 DOI: 10.1186/s12876-023-03116-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND & AIMS With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. METHODS 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman's correlation and AUROC analyses. RESULTS Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman's rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65-0.83), and 0.67(95%CI 0.56-0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. CONCLUSIONS sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.
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Affiliation(s)
- Florian F Hildenbrand
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Stadtspital Zurich, Zurich, Switzerland
| | - Barbara Illi
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Stefanie von Felten
- Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Jacqueline Bachofner
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Joanna Gawinecka
- Institute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Arnold von Eckardstein
- Institute of Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Beat Müllhaupt
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | | | - Sena Blümel
- Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
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Ma L, Yin L, Zhu H, Li J, Wang D. Two-dimensional vascularized liver organoid on extracellular matrix with defined stiffness for modeling fibrotic and normal tissues. J Tissue Eng 2024; 15:20417314241268344. [PMID: 39130682 PMCID: PMC11316963 DOI: 10.1177/20417314241268344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 07/18/2024] [Indexed: 08/13/2024] Open
Abstract
Antifibrotic drug screening requires evaluating the inhibitory effects of drug candidates on fibrotic cells while minimizing any adverse effects on normal cells. It is challenging to create organ-specific vascularized organoids that accurately model fibrotic and normal tissues for drug screening. Our previous studies have established methods for culturing primary microvessels and epithelial cells from adult tissues. In this proof-of-concept study, we used rats as a model organism to create a two-dimensional vascularized liver organoid model that comprised primary microvessels, epithelia, and stellate cells from adult livers. To provide appropriate substrates for cell culture, we engineered ECMs with defined stiffness to mimic the different stages of fibrotic tissues and normal tissues. We examined the effects of two TGFβ signaling inhibitors, A83-01 and pirfenidone, on the vascularized liver organoids on the stiff and soft ECMs. We found that A83-01 inhibited fibrotic markers while promoting epithelial genes of hepatocytes and cholangiocytes. However, it inhibited microvascular genes on soft ECM, indicating a detrimental effect on normal tissues. Furthermore, A83-01 significantly promoted the expression of markers of stem cells and cancers, increasing the potential risk of it being a carcinogen. In contrast, pirfenidone, an FDA-approved compound for antifibrotic treatments, did not significantly affect all the genes examined on soft ECM. Although pirfenidone had minor effects on most genes, it did reduce the expression of collagens, the major components of fibrotic tissues. These results explain why pirfenidone can slow fibrosis progression with minor side effects in clinical trials. In conclusion, our study presents a method for creating vascularized liver organoids that can accurately mimic fibrotic and normal tissues for drug screening. Our findings provide valuable insights into the potential risks and benefits of using A83-01 and pirfenidone as antifibrotic drugs. This method can be applied to other organs to create organ-specific vascularized organoids for drug development.
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Affiliation(s)
- Lei Ma
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Medical College, Qingdao University, Qingdao, China
| | - Lin Yin
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Medical College, Qingdao University, Qingdao, China
| | - Hai Zhu
- Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
| | - Jing Li
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Medical College, Qingdao University, Qingdao, China
| | - Dong Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Medical College, Qingdao University, Qingdao, China
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Alghamdi AS, Alghamdi H, Alserehi HA, Babatin MA, Alswat KA, Alghamdi M, AlQutub A, Abaalkhail F, Altraif I, Alfaleh FZ, Sanai FM. SASLT guidelines: Update in treatment of hepatitis C virus infection, 2024. Saudi J Gastroenterol 2024; 30:S1-S42. [PMID: 38167232 PMCID: PMC10856511 DOI: 10.4103/sjg.sjg_333_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/27/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
ABSTRACT Hepatitis C virus (HCV) infection has been a major global health concern, with a significant impact on public health. In recent years, there have been remarkable advancements in our understanding of HCV and the development of novel therapeutic agents. The Saudi Society for the Study of Liver Disease and Transplantation formed a working group to develop HCV practice guidelines in Saudi Arabia. The methodology used to create these guidelines involved a comprehensive review of available evidence, local data, and major international practice guidelines regarding HCV management. This updated guideline encompasses critical aspects of HCV care, including screening and diagnosis, assessing the severity of liver disease, and treatment strategies. The aim of this updated guideline is to assist healthcare providers in the management of HCV in Saudi Arabia. It summarizes the latest local studies on HCV epidemiology, significant changes in virus prevalence, and the importance of universal screening, particularly among high-risk populations. Moreover, it discusses the promising potential for HCV elimination as a public health threat by 2030, driven by effective treatment and comprehensive prevention strategies. This guideline also highlights evolving recommendations for advancing disease management, including the treatment of HCV patients with decompensated cirrhosis, treatment of those who have previously failed treatment with the newer medications, management in the context of liver transplantation and hepatocellular carcinoma, and treatment for special populations.
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Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Haleema A. Alserehi
- General Directorate of Communicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
| | - Mohammed A. Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Khalid A. Alswat
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Adel AlQutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Hepatology Section, Hepatobiliary Sciences and Organs Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | | | - Faisal M. Sanai
- Liver Disease Research Center, and Riyadh, Saudi Arabia
- Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
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Herlihy T, Moran M, Heeney A, Okhai H, De Franceso D, Cronin C, Feeney E, Houlihan D, Stewart S, Cotter AG. A comparison of transient elastography with acoustic radiation force impulse elastography for the assessment of liver health in patients with chronic hepatitis C: Baseline results from the TRACER study. ULTRASOUND (LEEDS, ENGLAND) 2023; 31:244-253. [PMID: 37929249 PMCID: PMC10621485 DOI: 10.1177/1742271x221139181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 10/18/2022] [Indexed: 11/07/2023]
Abstract
Background Liver stiffness measurements can be used to assess liver fibrosis and can be acquired by transient elastography using FibroScan® and with Acoustic Radiation Force Impulse imaging. The study aimed to establish liver stiffness measurement scores using FibroScan® and Acoustic Radiation Force Impulse in a chronic hepatitis C cohort and to explore the correlation and agreement between the scores and the factors influencing agreement. Methods Patients had liver stiffness measurements acquired with FibroScan® (right lobe of liver) and Acoustic Radiation Force Impulse (right and left lobe of liver). We used Spearman's correlation to explore the relationship between FibroScan® and Acoustic Radiation Force Impulse scores. A Bland-Altman plot was used to evaluate bias between the mean percentage differences of FibroScan® and Acoustic Radiation Force Impulse scores. Univariable and multivariable analyses were used to assess how factors such as body mass index, age and gender influenced the agreement between liver stiffness measurements. Results Bland-Altman showed the average (95% CI) percentage difference between FibroScan® and Acoustic Radiation Force Impulse scores was 27.5% (17.8, 37.2), p < 0.001. There was a negative correlation between the average and percentage difference of the FibroScan® and Acoustic Radiation Force Impulse scores ( r (95% CI) = -0.41 (-0.57, -0.21), p < 0.001), thus showing that percentage difference gets smaller for greater FibroScan® and Acoustic Radiation Force Impulse scores. Body mass index was the biggest influencing factor on differences between FibroScan® and Acoustic Radiation Force Impulse (r = 0.12 (0.01, 0.23), p = 0.05). Acoustic Radiation Force Impulse scores at segment 5/8 and the left lobe showed good correlation (r (95% CI) = 0.83 (0.75, 0.89), p < 0.001). Conclusion FibroScan® and Acoustic Radiation Force Impulse had similar predictive values for the assessment of liver stiffness in patients with chronic hepatitis C infection; however, the level of agreement varied across lower and higher scores.
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Affiliation(s)
- Therese Herlihy
- School of Medicine, University College Dublin, Dublin, Ireland
- Mater Misericordiae University Hospital, Dublin, Ireland
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
| | - Mary Moran
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Aoife Heeney
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - Hajra Okhai
- Institute for Global Health, University College London, London, UK
| | | | - Carmel Cronin
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - Eoin Feeney
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
- St. Vincent’s University Hospital, Dublin, Ireland
| | | | - Stephen Stewart
- School of Medicine, University College Dublin, Dublin, Ireland
- Mater Misericordiae University Hospital, Dublin, Ireland
| | - Aoife G Cotter
- School of Medicine, University College Dublin, Dublin, Ireland
- Mater Misericordiae University Hospital, Dublin, Ireland
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
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Rahmani G, O'Sullivan GJ. Acute and chronic venous occlusion. Br J Radiol 2023; 96:20230242. [PMID: 37750946 PMCID: PMC10607425 DOI: 10.1259/bjr.20230242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/04/2023] [Accepted: 08/04/2023] [Indexed: 09/27/2023] Open
Abstract
This review article provides an overview of acute and chronic venous occlusion, a condition that can cause significant morbidity and mortality if not diagnosed and treated promptly. The article begins with an introduction to the anatomy of the venous system, followed by a discussion of the causes and clinical features of venous occlusion. The diagnostic tools available for the assessment of venous occlusion, including imaging modalities such as ultrasound, CT, and MRI, are then discussed, along with their respective advantages and limitations. The article also covers the treatment options for acute and chronic venous occlusion, including anticoagulant therapy and endovascular interventions. This review aims to provide radiologists with an updated understanding of the pathophysiology, diagnosis, and management of acute and chronic venous occlusion.
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Affiliation(s)
- George Rahmani
- Department of Interventional Radiology, Galway University Hospitals, Galway, Ireland
| | - Gerard J O'Sullivan
- Department of Interventional Radiology, Galway University Hospitals, Galway, Ireland
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Rowland M, Drummond J, Connolly L, Daly E, McCormick PA, Bourke B. The natural history of cystic fibrosis liver disease a prospective cohort study. J Cyst Fibros 2023; 22:1054-1061. [PMID: 37495468 DOI: 10.1016/j.jcf.2023.07.002] [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: 10/28/2022] [Revised: 05/15/2023] [Accepted: 07/05/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND Our understanding of the natural history of cystic fibrosis liver disease (CFLD) is limited, leading to uncertainty for patients their families and clinicians when liver abnormalities are identified. AIM to determine the incidence of CFLD, identify risk factors and document the natural history of liver abnormalities in cystic fibrosis (CF). METHODS The Irish longitudinal study of CFLD (ILSCFLD) prospectively enrolled 95% of children with CF in 2007. Their liver disease status was classified as (i) advanced liver disease with portal hypertension (CFLD). (ii) nonspecific cystic fibrosis liver disease (NSCFLD) (iii) no liver disease (NoLD) RESULTS: 480/522 (91.9%) children were followed for a median 8.53 years IQR 1.28, of whom 35 (7.29%) had CFLD, 110 (22.9%) NSCFLD and 335 (69.79%) had NoLD. At follow-up 28/445 (6.29%) participants without CFLD at baseline, progressed to CFLD (Incidence 7.51/1000 person years (Pyrs) (95%CI 4.99-10.86). Of these 25/28(89.28%) were <10 years. No participant >10 years of age without clinical or radiological evidence of liver disease at baseline progressed to CFLD. During follow-up 18/35(51.43%) participants with CFLD died or received a transplant, MTx rate 7.75/100 Pyrs (95%CI 4.59-12.25) compared to NSCFLD 2.33/100 Pyrs (95%CI 1.44-3.56) and NoLD 1.13/100 Pyrs (95%CI 0.77-1.59). CFLD was an independent risk factor for mortality in CF. Children with CFLD also had a shorter life expectancy. CONCLUSION The incidence of CFLD was highest in children under10 years. Children over10 years, with normal hepatic function did not develop CFLD. Research to identify the cause and improve outcome should focus on young children.
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Affiliation(s)
- Marion Rowland
- School of Medicine, University College Dublin, Belfield Dublin 4, Ireland; Catherine McAuley Research Centre, Nelson Street, Dublin 7, Ireland.
| | - Jennifer Drummond
- School of Medicine, University College Dublin, Belfield Dublin 4, Ireland; Catherine McAuley Research Centre, Nelson Street, Dublin 7, Ireland
| | - Lucy Connolly
- School of Medicine, University College Dublin, Belfield Dublin 4, Ireland; Catherine McAuley Research Centre, Nelson Street, Dublin 7, Ireland
| | | | - P Aiden McCormick
- School of Medicine, University College Dublin, Belfield Dublin 4, Ireland; St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
| | - Billy Bourke
- School of Medicine, University College Dublin, Belfield Dublin 4, Ireland; Children's Health Ireland at Crumlin, Crumlin Dublin 12, Ireland; National Children's Research Centre, Crumlin Dublin 12, Ireland; Conway Institute of Biomedical and Molecular Science, University College Dublin Belfield, Dublin 4, Ireland
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Nishio T, Taura K, Koyama Y, Ishii T, Hatano E. Current status of preoperative risk assessment for posthepatectomy liver failure in patients with hepatocellular carcinoma. Ann Gastroenterol Surg 2023; 7:871-886. [PMID: 37927928 PMCID: PMC10623981 DOI: 10.1002/ags3.12692] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/08/2023] [Accepted: 05/03/2023] [Indexed: 11/07/2023] Open
Abstract
Liver resection is an effective therapeutic option for patients with hepatocellular carcinoma. However, posthepatectomy liver failure (PHLF) remains a major cause of hepatectomy-related mortality, and the accurate prediction of PHLF based on preoperative assessment of liver functional reserve is a critical issue. The definition of PHLF proposed by the International Study Group for Liver Surgery has gained acceptance as a standard grading criterion. Liver function can be estimated using a variety of parameters, including routine blood biochemical examinations, clinical scoring systems, dynamic liver function tests, liver stiffness and fibrosis markers, and imaging studies. The Child-Pugh score and model for end-stage liver disease scores are conventionally used for estimating liver decompensation, although the alternatively developed albumin-bilirubin score shows superior performance for predicting hepatic dysfunction. Indocyanine green clearance, a dynamic liver function test mostly used in Japan and other Asian countries, serves as a quantitative estimation of liver function reserve and helps determine indications for surgical procedures according to the estimated risk of PHLF. In an attempt to improve predictive accuracy, specific evaluation of liver fibrosis and portal hypertension has gained popularity, including liver stiffness measurements using ultrasonography or magnetic resonance elastography, as well as noninvasive fibrosis markers. Imaging modalities, including Tc-99m-labeled galactosyl serum albumin scintigraphy and gadolinium-enhanced magnetic resonance imaging, are used for preoperative evaluation in combination with liver volume. This review aims to provide an overview of the usefulness of current options for the preoperative assessment of liver function in predicting PHLF.
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Affiliation(s)
- Takahiro Nishio
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of Gastroenterological Surgery and OncologyKitano HospitalOsakaJapan
| | - Yukinori Koyama
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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Sushaal CR, Patil VM, Patil S. The role of sound touch elastography in assessment of liver fibrosis in chronic liver disease keeping APRI as the reference standard. Abdom Radiol (NY) 2023; 48:3373-3381. [PMID: 37620709 DOI: 10.1007/s00261-023-04018-5] [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: 04/30/2023] [Revised: 07/30/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023]
Abstract
PURPOSE The study aims to determine the role of Sound Touch Elastography [STE] technique in staging liver fibrosis and predicting clinically significant gastro-esophageal varices among patients with chronic liver disease [CLD] keeping aspartate aminotransferase to platelet ratio index [APRI] as the reference standard. METHODS A prospective short-term study including 60 eligible patients with CLD were staged as non-significant fibrosis [NSF], significant fibrosis [SF] and cirrhosis [C] based on APRI values. STE was performed on each patient obtaining multiple readings as per pre-defined standards. The intra-observer reliability between each measurement and its association with APRI staging was evaluated using relevant statistical variables. Further, Youden's index was used to define the optimum cut-off values on STE in differentiating the stages of fibrosis and in predicting clinically significant gastro-esophageal varices. RESULTS Based on APRI cut-off values, 41.7% [n = 25] of the study population had cirrhosis, while 45% [n = 27] had significant fibrosis and 13.3% [n = 8] had NSF. The STE values in kPa showed a positive correlation with APRI values [(rs) = 0.837, p < 0.001]. The intra-class correlation estimates based on a mean rating [k = 5] was found to be 0.97 [0.95-0.99], implying an excellent agreement between the measurements. Optimum cut-off values in staging SF and C were 7.26 kPa [J = 0.73, sensitivity-85.19%, specificity-87.5%; 95% CI] and 13.79 kPa [J = 0.84, sensitivity-96.0%, specificity-88.89%; 95% CI]. The AUROC for each of these stages were 0.926 [0.785-0.987] and 0.976 [0.890-0.999], respectively. 23.3% [n = 14] of the study population had clinically significant gastro-esophageal varices with a value above 18.84 kPa [J = 0.88] showing a sensitivity of 92.85% and a specificity of 95.65% in predicting the same. CONCLUSION The novel STE technique shows good accuracy in staging liver fibrosis as determined by APRI values and in prediction of clinically significant gastro-esophageal varices with excellent reliability. It shows promising prospects and can be integrated widely in clinical practice for assessment and staging of fibrosis in CLD.
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Affiliation(s)
- C R Sushaal
- Department of Radio-Diagnosis, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, 585105, India.
| | - Vikram M Patil
- Department of Radio-Diagnosis, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, 585105, India
| | - Shivanand Patil
- Department of Gastroenterology, Mahadevappa Rampure Medical College, Kalaburagi, Karnataka, 585105, India
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Bojanic K, Bogojevic MS, Vukadin S, Sikora R, Ivanac G, Lucic NR, Smolic M, Tabll AA, Wu GY, Smolic R. Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update. J Clin Transl Hepatol 2023; 11:1228-1238. [PMID: 37577224 PMCID: PMC10412701 DOI: 10.14218/jcth.2022.00365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/04/2022] [Accepted: 02/27/2023] [Indexed: 07/03/2023] Open
Abstract
Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response. The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.
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Affiliation(s)
- Kristina Bojanic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek-Baranja County, Osijek, Croatia
| | | | - Sonja Vukadin
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Renata Sikora
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek-Baranja County, Osijek, Croatia
| | - Gordana Ivanac
- University Hospital Dubrava, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Nikola Raguz Lucic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Martina Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Center, Giza, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt
| | - George Y. Wu
- University of Connecticut Health Center, Farmington, CT, USA
| | - Robert Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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Grinspan GA, Fernandes de Oliveira L, Brandao MC, Pomi A, Benech N. Load sharing between synergistic muscles characterized by a ligand-binding approach and elastography. Sci Rep 2023; 13:18267. [PMID: 37880279 PMCID: PMC10600237 DOI: 10.1038/s41598-023-45037-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 10/14/2023] [Indexed: 10/27/2023] Open
Abstract
The skeletal muscle contraction is determined by cross-bridge formation between the myosin heads and the actin active sites. When the muscle contracts, it shortens, increasing its longitudinal shear elastic modulus ([Formula: see text]). Structurally, skeletal muscle can be considered analogous to the molecular receptors that form receptor-ligand complexes and exhibit specific ligand-binding dynamics. In this context, this work aims to apply elastography and the ligand-binding framework to approach the possible intrinsic mechanisms behind muscle synergism. Based on the short-range stiffness principle and the acoustic-elasticity theory, we define the coefficient [Formula: see text], which is directly related to the fraction saturation of molecular receptors and links the relative longitudinal deformation of the muscle to its [Formula: see text]. We show that such a coefficient can be obtained directly from [Formula: see text] estimates, thus calculating it for the biceps brachii, brachioradialis, and brachialis muscles during isometric elbow flexion torque (τ) ramps. The resulting [Formula: see text] curves were analyzed by conventional characterization methods of receptor-ligand systems to study the dynamical behavior of each muscle. The results showed that, depending on muscle, [Formula: see text] exhibits typical ligand-binding dynamics during joint torque production. Therefore, the above indicates that these different behaviors describe the longitudinal shortening pattern of each muscle during load sharing. As a plausible interpretation, we suggested that this could be related to the binding kinetics of the cross-bridges during their synergistic action as torque increases. Likewise, it shows that elastography could be useful to assess contractile processes at different scales related to the change in the mechanical properties of skeletal muscle.
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Affiliation(s)
- Gustavo A Grinspan
- Sección Biofísica y Biología de Sistemas, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay.
- Laboratorio de Acústica Ultrasonora, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay.
| | - Liliam Fernandes de Oliveira
- Laboratório de Análise do Movimento e Fisiologia do Exercício, Programa de Engenharia Biomédica, Universidade Federal do Rio de Janeiro, Av. Horácio Macedo 2030, Rio de Janeiro, 21941-590, Brazil
| | - Maria Clara Brandao
- Laboratório de Análise do Movimento e Fisiologia do Exercício, Programa de Engenharia Biomédica, Universidade Federal do Rio de Janeiro, Av. Horácio Macedo 2030, Rio de Janeiro, 21941-590, Brazil
| | - Andrés Pomi
- Sección Biofísica y Biología de Sistemas, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay
| | - Nicolás Benech
- Laboratorio de Acústica Ultrasonora, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay
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Fiordaliso M, Marincola G, Pala B, Muraro R, Mazzone M, Di Marcantonio MC, Mincione G. A Narrative Review on Non-Cirrohotic Portal Hypertension: Not All Portal Hypertensions Mean Cirrhosis. Diagnostics (Basel) 2023; 13:3263. [PMID: 37892084 PMCID: PMC10606323 DOI: 10.3390/diagnostics13203263] [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: 08/30/2023] [Revised: 10/17/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.
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Affiliation(s)
- Michele Fiordaliso
- Department of Medicine and Ageing Sciences, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy;
| | - Giuseppe Marincola
- Bariatric and Metabolic Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy;
| | - Barbara Pala
- Division of Cardiology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa, 1035/1039, 00189 Rome, Italy;
| | - Raffaella Muraro
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Mariangela Mazzone
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Maria Carmela Di Marcantonio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
| | - Gabriella Mincione
- Department of Innovative Technologies in Medicine & Dentistry, University “G. D’Annunzio” of Chieti–Pescara, Via dei Vestini 29, 66100 Chieti, Italy; (R.M.); (M.M.); (M.C.D.M.)
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Chouari T, Merali N, La Costa F, Santol J, Chapman S, Horton A, Aroori S, Connell J, Rockall TA, Mole D, Starlinger P, Welsh F, Rees M, Frampton AE. The Role of the Multiparametric MRI LiverMultiScan TM in the Quantitative Assessment of the Liver and Its Predicted Clinical Applications in Patients Undergoing Major Hepatic Resection for Colorectal Liver Metastasis. Cancers (Basel) 2023; 15:4863. [PMID: 37835557 PMCID: PMC10571783 DOI: 10.3390/cancers15194863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 08/05/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.
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Affiliation(s)
- Tarak Chouari
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Nabeel Merali
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Francesca La Costa
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Jonas Santol
- Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, 1090 Vienna, Austria
- Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
| | - Shelley Chapman
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Alex Horton
- Department of Radiology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
| | - Somaiah Aroori
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery and Transplant Surgery, Derriford Hospital, Plymouth PL6 8DH, UK
| | | | - Timothy A. Rockall
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
| | - Damian Mole
- Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH10 5HF, UK
- Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH105HF, UK
| | - Patrick Starlinger
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN 55902, USA
- Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
- Department of Surgery, Medical University of Vienna, General Hospital, 1090 Vienna, Austria
| | - Fenella Welsh
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Myrddin Rees
- Hepato-Biliary Unit, Hampshire Hospitals Foundation Trust, Basingstoke, Hampshire RG24 9NA, UK
| | - Adam E. Frampton
- MATTU, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK; (T.C.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK
- Oncology Section, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK
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48
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Bhattacharyya M, Nickols-Richardson SM, Miller AL, Bhattacharyya R, Frankhauser F, Miller LE. Prevalence and Determinants of Undiagnosed Liver Steatosis and Fibrosis in a Nationally Representative Sample of US Adults. Cureus 2023; 15:e46783. [PMID: 37954822 PMCID: PMC10633855 DOI: 10.7759/cureus.46783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2023] [Indexed: 11/14/2023] Open
Abstract
Background Chronic liver diseases account for approximately 1.9 million deaths globally every year and negatively affect health-related quality of life. Early detection of liver disease may enable timely treatment, potentially improving patient outcomes. This study aimed to determine the prevalence and determinants of liver steatosis and fibrosis in US adults with no previously diagnosed liver condition. Methods We conducted an observational, nationally representative, cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) conducted from January 2017 to March 2020. Study participants were 7,391 adults aged 21 and older with no history of diagnosed liver disorders who underwent vibration-controlled transient elastography (VCTE) to determine liver steatosis and fibrosis. Controlled attenuation parameter (CAP) values between 248 and 267 dB/m were classified as mild steatosis, and those over 267 dB/m as advanced steatosis. Liver stiffness measurement (LSM) values between 7.65 and 13 kPa were classified as moderate/severe fibrosis, and those over 13 kPa as cirrhosis. Covariates included age, sex, race, body mass index (BMI), diabetes mellitus, kidney disease, smoking history, alcohol intake, alanine aminotransferase (ALT), aspartate aminotransferase (AST), physical activity, sedentary time, and sleep time. The associations of subject characteristics with liver CAP and LSM were evaluated using survey multivariable linear regression. Shapley Additive Explanations values determined the relative importance of each attribute in the model. The discriminative performance of classification models was assessed using the area under the receiver operating characteristic (AUROC) curve. Results The population prevalence of liver steatosis was 57.2% (10.2% mild; 47.0% advanced). The relative importance of covariates in predicting liver CAP was 63.1% for BMI, 10.7% for ALT, and less than 10% for the other covariates. The prevalence of significant fibrosis was 11.4% (8.3% moderate/severe fibrosis; 3.1% cirrhosis). The relative importance of covariates in predicting LSM was 67.3% for BMI and less than 10% for the other covariates. BMI alone demonstrated acceptable discriminative performance in classifying varying severities of steatosis and fibrosis (AUROC range 72%-78%) at cutoffs between 28 and 33 kg/m2. Conclusions Undiagnosed chronic liver disease based on VCTE findings is highly prevalent among US adults, particularly in obese individuals. Efforts to increase awareness about liver disease and to reconsider existing BMI thresholds for liver disease screening may be warranted.
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Affiliation(s)
| | - Sharon M Nickols-Richardson
- Food Science & Human Nutrition, Division of Nutritional Sciences, College of Agricultural, Consumer & Environmental Sciences, University of Illinois, Urbana-Champaign, Urbana, USA
| | - Anna L Miller
- Clinical Research, Miller Scientific, Johnson City, USA
| | - Ruemon Bhattacharyya
- Public Affairs and Economics, University of California Los Angeles, Los Angeles, USA
| | - Frederick Frankhauser
- Pharmaceutical Business & Administrative Sciences, Massachusetts College of Pharmacy and Health Sciences, Boston, USA
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Saha S, Ray S, Mandal A, Das U, Bhattacharya T, Shireen Z, Sarkar S, Sharma RD, Ghosh S, Dey S. Enhanced inflammasome-mediated inflammation and impaired autophagy in peripheral blood mononuclear cells is associated with non-alcoholic fatty liver disease severity. Life Sci 2023; 329:121911. [PMID: 37429416 DOI: 10.1016/j.lfs.2023.121911] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/01/2023] [Accepted: 07/03/2023] [Indexed: 07/12/2023]
Abstract
AIMS Identification of the progress of non-alcoholic fatty liver disease (NAFLD) is crucial for their effective treatment. Circulating peripheral blood mononuclear cells (PBMC) could be a surrogate monitor instead of complicated and expensive biopsies. Changes in immuno-metabolic status in NAFLD patients may be reflected by an expression of different PBMC-specific molecular markers. It was hypothesized that impaired autophagy with enhanced inflammasome activation is a critical molecular event in PBMC that could contribute to systemic inflammation associated with NAFLD progression. MAIN METHODS A cross-sectional study with a sample size of 50 subjects were undertaken from a governmental facility in Kolkata, India. Major anthropometric, biochemical, and dietary parameters were recorded. Cellular and serum samples of NAFLD patients were analyzed for oxidative stress, inflammation, inflammasome activation, and autophagic flux by western blot, flow cytometry, immunocytochemistry. KEY FINDINGS Baseline anthropometric and clinical parameters were found associated with NAFLD severity. Elevated systemic inflammation was reflected by higher proinflammatory markers like iNOS, Cox-2, IL-6, TNF-α, IL-1β, hsCRP in the serum of NAFLD subjects (p < 0.05). ROS-induced NLRP3 inflammasomes marker proteins were upregulated (p < 0.05) in PBMC along with NAFLD severity. Expression of autophagic markers such as LC3B, Beclin-1 and its regulator pAMPKα were found diminished (p < 0.05) with a concomitant rise of p62. Colocalization of NLRP3 with LC3B proteins in PBMC was found diminished along NAFLD severity. SIGNIFICANCE Present data provide mechanistic evidence of impaired autophagy and intracellular ROS triggered inflammasome activation in PBMC, which could potentially exacerbate NAFLD severity.
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Affiliation(s)
- Samrat Saha
- University of Calcutta, Department of Physiology, Kolkata-700009, India
| | - Sujay Ray
- R.G Kar Medical College and Hospital, Department of Gastroenterology, Kolkata-700004, India
| | - Arpan Mandal
- Sarat Chandra Chattopadhyay Government Medical College, Uluberia, Howrah-711315, India
| | - Ujjal Das
- University of Calcutta, Department of Physiology, Kolkata-700009, India
| | | | - Zofa Shireen
- University of Calcutta, Department of Physiology, Kolkata-700009, India
| | - Sankalita Sarkar
- University of Calcutta, Department of Physiology, Kolkata-700009, India
| | - Rakhi Dey Sharma
- Belda College, Department of Physiology, Belda, Paschim Medinipur-721424, India
| | - Saurabh Ghosh
- Indian Statistical Institute, Human Genetics Unit, Kolkata-700108, India
| | - Sanjit Dey
- University of Calcutta, Department of Physiology, Kolkata-700009, India.
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50
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Cinque F, Saeed S, Kablawi D, Ramos Ballesteros L, Elgretli W, Moodie EEM, Price C, Monteith K, Cooper C, Walmsley SL, Pick N, Murray MCM, Cox J, Kronfli N, Costiniuk CT, de Pokomandy A, Routy JP, Lebouché B, Klein MB, Sebastiani G. Role of fatty liver in the epidemic of advanced chronic liver disease among people with HIV: protocol for the Canadian LIVEHIV multicentre prospective cohort. BMJ Open 2023; 13:e076547. [PMID: 37607785 PMCID: PMC10445396 DOI: 10.1136/bmjopen-2023-076547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 08/08/2023] [Indexed: 08/24/2023] Open
Abstract
INTRODUCTION Advanced chronic liver disease (ACLD) is a major cause of death for people with HIV (PWH). While viral hepatitis coinfections are largely responsible for this trend, metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging concern for PWH. We aimed to assess the contribution of MASLD to incident ACLD in PWH. METHODS AND ANALYSIS This multicentre prospective observational cohort study will enrol 968 consecutive HIV monoinfected patients from four Canadian sites, excluding subjects with alcohol abuse, liver disease other than MASLD, or ACLD at baseline. Participants will be followed annually for 4 years by clinical evaluation, questionnaires, laboratory testing and Fibroscan to measure liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). The primary outcome will be incidence of ACLD, defined as LSM>10 kPa, by MASLD status, defined as CAP≥285 dB/m with at least one metabolic abnormality, and to develop a score to classify PWH according to their risk of ACLD. Secondary outcomes will include health-related quality of life (HRQoL) and healthcare resource usage. Kaplan-Meier survival method and Cox proportional hazards regression will calculate the incidence and predictors of ACLD, respectively. Propensity score methods and marginal structural models will account for time-varying exposures. We will split the cohort into a training set (to develop the risk score) and a validation set (for validation of the score). HRQoL scores and healthcare resource usage will be compared by MASLD status using generalised linear mixed effects model. ETHICS AND DISSEMINATION This protocol has been approved by the ethics committees of all participating institutions. Written informed consent will be obtained from all study participants. The results of this study will be shared through scientific publications and public presentations to advocate for the inclusion of PWH in clinical trials of MASLD-targeted therapies and case-finding of ACLD in PWH.
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Affiliation(s)
- Felice Cinque
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Sahar Saeed
- Public Health Sciences, Queen's University, Kingston, Ontario, Canada
| | - Dana Kablawi
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Luz Ramos Ballesteros
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Wesal Elgretli
- Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada
| | - Erica E M Moodie
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Colleen Price
- Canadian HIV/AIDS and Chronic Pain Society, Ottawa, Ontario, Canada
| | | | - Curtis Cooper
- Department of Medicine, Division of Infectious Diseases, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Sharon L Walmsley
- Department of Medicine, Division of Infectious Diseases, University of Toronto, Toronto, Ontario, Canada
| | - Neora Pick
- Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Melanie C M Murray
- Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Joseph Cox
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Nadine Kronfli
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
| | | | - Alexandra de Pokomandy
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
| | - Jean-Pierre Routy
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
| | - Bertrand Lebouché
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Department of Family Medicine, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada
| | - Marina B Klein
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Giada Sebastiani
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
- Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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