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Nishimura T, Tada T, Akita T, Kondo R, Suzuki Y, Imajo K, Kokubu S, Abe T, Kuroda H, Hirooka M, Hiasa Y, Nogami A, Nakajima A, Ogawa S, Toyoda H, Oeda S, Takahashi H, Eguchi Y, Sugimoto K, Yano H, Tanaka J, Moriyasu F, Kage M, Kumada T, Iijima H. Diagnostic performance of attenuation imaging versus controlled attenuation parameter for hepatic steatosis with MRI-based proton density fat fraction as the reference standard: a prospective multicenter study. J Gastroenterol 2025; 60:727-737. [PMID: 39992415 PMCID: PMC12095409 DOI: 10.1007/s00535-025-02224-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/02/2025] [Indexed: 02/25/2025]
Abstract
BACKGROUND Attenuation Imaging (ATI) and controlled attenuation parameter (CAP) are non-invasive ultrasound-based methods for diagnosing hepatic steatosis. However, reports on the clinical usefulness of ATI are limited. We aimed to compare the ability of ATI and CAP to diagnose hepatic steatosis with magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) as the reference standard. METHODS We performed a prospective multicenter study of 562 patients with chronic liver disease who underwent ATI, CAP, and MRI-PDFF. Patients with skin-to-liver capsule distance (SCD) ≤ 25 mm underwent CAP with an M probe; those with SCD > 25 mm underwent CAP with an XL probe. MRI-PDFF was used as the reference standard: S0 corresponds to MRI-PDFF < 5.2%, S1 to 5.2% ≤ MRI-PDFF < 11.3%, S2 to 11.3% ≤ MRI-PDFF < 17.1%, and S3 to MRI-PDFF ≥ 17.1%. RESULTS The correlation coefficients for ATI and MRI-PDFF stratified by body mass index (< 30, ≥ 30 kg/m2), SCD (< 25, ≥ 25 mm), 2-dimensional share wave elastography (< 1.8 m/s), fibrosis-4 index (≤ 2.67), albumin-bilirubin score (< - 2.60) and type IV collagen 7 s (< 5.0 ng/ml) were significantly higher than those for CAP and MRI-PDFF. Areas under the receiver operating characteristics (95% CI) for ATI and CAP were 0.895 (0.869-0.922) and 0.845 (0.809-0.881) for ≥ S1 steatosis, 0.944 (0.926-0.963) and 0.881(0.852-0.910) for ≥ S2 steatosis, and 0.928 (95% CI 0.906-0.950) and 0.860 (95% CI 0.829-0.890) for S3 steatosis. ATI had higher diagnostic performance for all hepatic steatosis grades than CAP. CONCLUSIONS ATI is a more useful non-invasive method for diagnosing hepatic steatosis than CAP.
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Affiliation(s)
- Takashi Nishimura
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Japan
- Ultrasound Imaging Center, Hyogo Medical University Hospital, Nishinomiya, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanease Red Cross Himeji Hospital, Himeji, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Reiichiro Kondo
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Yasuaki Suzuki
- Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan
| | - Kento Imajo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan
| | - Shigehiro Kokubu
- Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan
| | - Tamami Abe
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan
| | - Asako Nogami
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Sadanobu Ogawa
- Department of Clinical Research, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Oeda
- Liver Center, Saga Medical School, Saga University, Saga, Japan
- Department of Laboratory Medicine, Saga University Hospital, Saga, Japan
| | | | - Yuichiro Eguchi
- Liver Center, Saga Medical School, Saga University, Saga, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Fuminori Moriyasu
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan
| | - Masayoshi Kage
- Center for Innovative Cancer Therapy, Kurume University Research, Kurume, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, 1-1 Mukogawa-cho, Nishinomiya, Japan.
- Ultrasound Imaging Center, Hyogo Medical University Hospital, Nishinomiya, Japan.
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Fujiwara Y, Kuroda H, Abe T, Nagasawa T, Nakaya I, Ito A, Watanabe T, Yusa K, Sato H, Suzuki A, Endo K, Yoshida Y, Oikawa T, Kakisaka K, Sawara K, Tada T, Miyasaka A, Oguri T, Kamiyama N, Matsumoto T. Impact of shear wave elastography and attenuation imaging for predicting life-threatening event in patients with metabolic dysfunction-associated steatotic liver disease. Sci Rep 2025; 15:4547. [PMID: 39915518 PMCID: PMC11802924 DOI: 10.1038/s41598-025-87974-w] [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: 09/27/2024] [Accepted: 01/23/2025] [Indexed: 02/09/2025] Open
Abstract
We aimed to elucidate the value of ultrasound-based biomarkers for predicting the major life-threatening events in metabolic dysfunction-associated steatotic liver disease (MASLD). We established a prospective cohort of 279 patients who underwent two-dimensional shear wave elastography (2D-SWE), ultrasound-guided attenuation parameter (UGAP). An area under the curve analysis was performed to determine the cutoff values of liver stiffness measurements (LSM) by 2D-SWE and attenuation coefficient (AC) by UGAP for a moderate fibrosis and a moderate steatosis. We then classified the cohort into Groups A (low LSM and low AC), B (low LSM and high AC), C (high LSM and high AC), and D (high LSM and low AC). We compared the incidence of events between the groups, and estimated the hazard ratios (HRs) with 95% confidence intervals (CIs). The LSM and AC cut off values were 8.37 kPa and 0.62 dB/cm/MHz, respectively. The cumulative incidence rate in Groups A, B, C, and D were 11.2%, 12.2%, 29.5%, and 31.0%/5years, respectively (p < 0.05). LSM (HRs = 1.20, 95%CIs: 1.09-1.32, p < 0.01), and AC (HRs = 1.62, 95%CIs: 1.04-2.51, p = 0.03) were associated with life-threatening events. A combination of 2D-SWE and UGAP may help identify patients with MASLD at high risk for subsequent life-threatening events.
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Affiliation(s)
- Yudai Fujiwara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
| | - Hidekatsu Kuroda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Tamami Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Tomoaki Nagasawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Ippeki Nakaya
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Asami Ito
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Takuya Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Kenji Yusa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Hiroki Sato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Akiko Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Kei Endo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Yuichi Yoshida
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Takayoshi Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Keisuke Kakisaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Kei Sawara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Toshifumi Tada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Akio Miyasaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
| | - Takuma Oguri
- Ultrasound General Imaging, GE HealthCare, Hino, Tokyo, Japan
| | | | - Takayuki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan
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Lonardo A, Ballestri S, Baffy G, Weiskirchen R. Liver fibrosis as a barometer of systemic health by gauging the risk of extrahepatic disease. METABOLISM AND TARGET ORGAN DAMAGE 2024; 4. [DOI: 10.20517/mtod.2024.42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
This review article proposes the theory that liver fibrosis, the abnormal accumulation of excessive extracellular matrix, is not just an indicator of liver disease but also a negative reflection of overall systemic health. Liver fibrosis poses a heavy financial burden on healthcare systems worldwide and can develop due to chronic liver disease from various causes, often due to sustained inflammation. Liver fibrosis may not generate symptoms and become apparent only when it reaches the stage of cirrhosis and is associated with clinically significant portal hypertension and leads to decompensation events or promotes the development of hepatocellular carcinoma. While chronic viral hepatitis and excessive alcohol consumption were once the primary causes of chronic liver disease featuring fibrosis, this role is now increasingly taken over by metabolic dysfunction-associated steatotic liver disease (MASLD). In MASLD, endothelial dysfunction is an essential component in pathogenesis, promoting the development of liver fibrosis, but it is also present in endothelial cells of other organs such as the heart, lungs, and kidneys. Accordingly, liver fibrosis is a significant predictor of liver-related outcomes, as well as all-cause mortality, cardiovascular risk, and extrahepatic cancer. Physicians should be aware that individuals seeking medical attention for reasons unrelated to liver health may also have advanced fibrosis. Early identification of these at-risk individuals can lead to a more comprehensive assessment and the use of various treatment options, both approved and investigational, to slow or reverse the progression of liver fibrosis.
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Jeong S, Park SJ, Na SK, Park SM, Song BC, Oh YH. Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan. Hepatobiliary Pancreat Dis Int 2024; 23:353-360. [PMID: 36870896 DOI: 10.1016/j.hbpd.2023.02.009] [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: 08/04/2022] [Accepted: 02/17/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score was recently developed with the intent to operationally define nonalcoholic fatty liver disease (NAFLD). However, there remained an external validation that confirmed its diagnostic performance, especially in patients with alcohol consumption or hepatitis virus infection. METHODS Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®. Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score, fatty liver index (FLI), and hepatic steatosis index (HSI). RESULTS K-NAFLD-moderate [adjusted odds ratio (aOR) = 2.53, 95% confidence interval (CI): 1.13-5.65] and K-NAFLD-high (aOR = 4.14, 95% CI: 1.69-10.13) groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics, and FLI-moderate and FLI-high groups revealed aORs of 2.05 (95% CI: 1.22-3.43) and 1.51 (95% CI: 0.78-2.90), respectively. In addition, the HSI was less predictive for Fibroscan®-defined fatty liver. Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection, and the adjusted area under curve values were comparable between K-NAFLD and FLI. CONCLUSIONS Externally validation of the K-NAFLD and FLI showed that these scores may be a useful, noninvasive, and non-imaging modality for the identification of fatty liver. In addition, these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.
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Affiliation(s)
- Seogsong Jeong
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; Department of Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam 13488, Korea
| | - Sun Jae Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea
| | - Seong Kyun Na
- Department of Internal Medicine, Inje University College of Medicine, Seoul 50834, Korea
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea; Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea
| | - Byung-Cheol Song
- Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Korea
| | - Yun Hwan Oh
- Department of Family Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Korea; Department of Family Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong 14353, Korea.
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Kumada T, Toyoda H, Ogawa S, Gotoh T, Suzuki Y, Sugimoto K, Yoshida Y, Kuroda H, Kamada Y, Sumida Y, Ito T, Akita T, Tanaka J. Severe hepatic steatosis promotes increased liver stiffness in the early stages of metabolic dysfunction-associated steatotic liver disease. Liver Int 2024; 44:1700-1714. [PMID: 38558221 DOI: 10.1111/liv.15920] [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: 10/31/2023] [Revised: 03/18/2024] [Accepted: 03/19/2024] [Indexed: 04/04/2024]
Abstract
BACKGROUND & AIMS The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. METHODS We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. RESULTS A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). CONCLUSIONS Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa).
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Affiliation(s)
- Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Sadanobu Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tatsuya Gotoh
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuaki Suzuki
- Department of Gastroenterology, Nayoro City General Hospital, Nayoro, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Yuichi Yoshida
- Department of Gastroenterology and Hepatology, Suita Municipal Hospital, Osaka, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
| | - Yoshihiro Kamada
- Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yoshio Sumida
- Department of Healthcare Management, International University of Health and Welfare, Tokyo, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Leão Filho HM. The impact of steatosis assessment in imaging. Radiol Bras 2024; 57:e3. [PMID: 38993966 PMCID: PMC11235060 DOI: 10.1590/0100-3984.2024.57.e3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2024] Open
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Kuo SZ, Loomba R. Letter: Are we forgetting the importance of steatosis in steatotic liver disease? Authors' reply. Aliment Pharmacol Ther 2024; 59:297-298. [PMID: 38153275 DOI: 10.1111/apt.17825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 11/21/2023] [Indexed: 12/29/2023]
Abstract
LINKED CONTENTThis article is linked to Kuo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17637 and https://doi.org/10.1111/apt.17759
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Affiliation(s)
- Selena Z Kuo
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
- Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
- Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
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Ferraioli G, Barr RG. Noninvasive assessment of liver steatosis with ultrasound techniques. MULTIPARAMETRIC ULTRASOUND FOR THE ASSESSMENT OF DIFFUSE LIVER DISEASE 2024:177-198. [DOI: 10.1016/b978-0-323-87479-3.00020-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Thomas M, Dighe M, Kolokythas O, Zecevic M, Wilson A, Erpelding T, Dubinsky TJ. Ultrasound Attenuation Imaging vs MRI-PDFF, Echogenicity and Liver Function for Assessing Degree of Steatosis in NAFLD and Non-NAFLD Patients. Ultrasound Q 2023; 39:188-193. [PMID: 37543732 DOI: 10.1097/ruq.0000000000000648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2023]
Abstract
ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.
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Kobyliak N, Dynnyk O, Savytska M, Solodovnyk O, Zakomornyi O, Оmеlchenko O, Kushnir A, Titorenko R. Accuracy of attenuation coefficient measurement (ACM) for real-time ultrasound hepatic steatometry: Comparison of simulator/phantom data with magnetic resonance imaging proton density fat fraction (MRI-PDFF). Heliyon 2023; 9:e20642. [PMID: 37818006 PMCID: PMC10560839 DOI: 10.1016/j.heliyon.2023.e20642] [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: 05/11/2023] [Revised: 10/03/2023] [Accepted: 10/03/2023] [Indexed: 10/12/2023] Open
Abstract
Objectives To evaluate the accuracy and reproducibility of real time ultrasound (US) steatometry with the Attenuation Coefficient (AC) measurement in comparison with magnetic resonance imaging with proton density software module (MRI-PDFF). Methods This study was conducted between January 2021 and October 2021. The comparison of instrumental methods for assessing and grading hepatic steatosis using a multimodal phantom simulator of different fat and water ratios was performed. The study involved 3 radiological centers. The steatophantom was simultaneously investigated using three methods: magnetic resonance imaging with proton density software module (MRI-PDFF) and 128-slice multidetector computed tomography, and then by 2 different US scanner for steatosis assessment via Measurement Attenuation Imaging (ATI) ant Attenuation Coefficient Measurement (ACM). Results Modeling of hepatic steatosis using a series of phantom simulators allows evidence-based medicine to determine the diagnostic accuracy of the latest US techniques for steatosis. The ACM and ATI of both US systems on phantoms correlated well with each other and with MRI-PDFF and, thus, can provide good diagnostic value in the assessment of hepatic steatosis. MDCT was less sensitive to mild steatosis than AC and MRI-PDFF. Conclusion Measurement of ACs in US studies by devices from different vendors compared to other modalities of radiological imaging (MDCT and MRI-PDFF) by special phantoms is an accurate and promising method for noninvasive quantification of hepatic steatosis.
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Affiliation(s)
- Nazarii Kobyliak
- Endocrinology Department, Bogomolets National Medical University, 01601, Kyiv, Ukraine
- Medical Laboratory CSD, 03022, Kyiv, Ukraine
| | - Oleh Dynnyk
- Medical Center “Institute of elastography” LLC, Kyiv, Ukraine
| | - Maryana Savytska
- Normal Physiology Department, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
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Liao Y, Liu L, Yang J, Zhou X, Teng X, Li Y, Wan Y, Yang J, Shi Z. Analysis of clinical features and identification of risk factors in patients with non-alcoholic fatty liver disease based on FibroTouch. Sci Rep 2023; 13:14812. [PMID: 37684380 PMCID: PMC10491815 DOI: 10.1038/s41598-023-41596-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Our aim was to explore the correlation between ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) based on FibroTouch (China) and clinical features in patients with non-alcoholic fatty liver disease (NAFLD), so as to provide a certain basis for the clinical application of FibroTouch in NAFLD. Hepatic steatosis and fibrosis in patients with NAFLD were graded according to FibroTouch, and the relationship between steatosis and fibrosis levels and clinical characteristics was retrospectively analyzed. Hepatic steatosis was positively related with weight, BMI, waist, hyperlipidemia, hyperuricemia, FBG, UA, TG, ALT, AST, GGT, LSM and hepatic fibrosis grading, and was negatively related with gender (male), age and AST/ALT ratio. Hepatic fibrosis was positively related with age, BMI, waist, hypertension, FBG, ALT, AST, GGT, NFS, APRI, FIB-4, UAP and hepatic steatosis grading, and was negatively related with blood platelet (PLT) counts. Moreover, BMI, waist, TG, ALT and LSM were independent risk factors of hepatic steatosis, while decreased PLT counts, AST and UAP were independent risk factors of hepatic fibrosis. Body mass parameters, metabolic risk factors and liver function indicators increase the risk of hepatic steatosis and fibrosis in patients with NAFLD, and UAP and LSM can interact with each other.
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Affiliation(s)
- Yan Liao
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China.
| | - Lei Liu
- Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiayao Yang
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
| | - Xiaoli Zhou
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
| | - Xiaoli Teng
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
| | - Yixi Li
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
| | - Ying Wan
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
| | - Jian Yang
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
| | - Zhaohong Shi
- Department of Gastroenterology, Wuhan No.1 Hospital, Wuhan, China
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Ye J, Lin Y, Shao C, Sun Y, Feng S, Zhong B. Comparisons of Insulin Resistance- and Steatosis-Based Scores in Monitoring Metabolic Associated Fatty Liver Disease Treatment Response. ANNALS OF NUTRITION & METABOLISM 2023; 79:448-459. [PMID: 37678173 DOI: 10.1159/000530531] [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: 02/25/2022] [Accepted: 10/28/2022] [Indexed: 09/09/2023]
Abstract
BACKGROUND Quantitative measurements of liver fat contents (LFCs) by magnetic resonance imaging derived-proton density fat fraction (MRI-PDFF) are accurate but limited by availability, convenience, and expense in the surveillance of metabolic associated fatty liver (MAFLD). Insulin resistance (IR) and steatosis-associated serum indices are useful in screening for MAFLD, but their value in monitoring MAFLD with or without chronic hepatitis B virus (CHB) infection remains unclear and we aimed to evaluate these scores in predicting changes in LFC. METHODS We conducted a prospective study between January 2015 and December 2021 with 620 consecutive participants with MAFLD (212 participants with CHB) who received a 24-week lifestyle intervention. The homeostasis model assessment of IR (HOMA-IR), HOMA2 index, glucose-insulin ratio, quantitative insulin sensitivity check index, fasting insulin resistance index, fatty liver index (FLI), hepatic steatosis index (HSI), liver fat score (LFS), visceral adiposity index, and triglycerides * glucose were calculated. RESULTS When using endpoints such as LFS improvements of ≥5% or 10% or escalations of ≥5%, LFS had the highest area under the curve (AUC) values at all endpoints for MAFLD alone (0.756, 95% CI: 0.707-0.805; 0.761, 95% CI: 0.705-0.818; 0.807, 95% CI: 0.713-0.901, all p < 0.05, respectively). With CHB, the FLI (AUC = 0.750) and HIS (AUC = 0.770) exhibited the highest AUCs between the former two outcomes, respectively, but no score could predict LFC escalation of ≥5%. CONCLUSION Among IR and steatosis scores, changes in LFC through lifestyle interventions can be captured with LFS possessing moderate precision but not in those with CHB.
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Affiliation(s)
- Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yansong Lin
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Congxian Shao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanhong Sun
- Department of Clinical Laboratories, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Kuo SZ, Cepin S, Bergstrom J, Siddiqi H, Jung J, Lopez S, Huang DQ, Taub P, Amangurbanova M, Loomba R. Clinical utility of liver fat quantification for determining cardiovascular disease risk among patients with type 2 diabetes. Aliment Pharmacol Ther 2023; 58:585-592. [PMID: 37431679 PMCID: PMC10792531 DOI: 10.1111/apt.17637] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 12/27/2022] [Accepted: 06/27/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are independent risk factors for cardiovascular disease (CVD). AIMS To examine the clinical utility of liver fat quantification for determining CVD risk among a well-phenotyped cohort of patients with T2DM. METHODS This was a cross-sectional analysis of a prospective cohort of adults aged ≥50 with T2DM. Liver fat was quantified with magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), an advanced imaging-based biomarker. Patients were stratified into a higher liver fat group (MRI-PDFF ≥ 14.6%), and a lower liver fat group (MRI-PDFF < 14.6%). The co-primary outcomes were CVD risk determined by Framingham and Atherosclerotic Cardiovascular Disease (ASCVD) risk scores. High CVD risk was defined by risk scores ≥20%. RESULTS Of the 391 adults (66% female) in this study, the mean (±SD) age was 64 (±8) years and BMI 30.8 (±5.2) kg/m2 , respectively. In multivariable analysis, adjusted for age, gender, race, and BMI, patients in the higher liver fat group had higher CVD risk [OR = 4.04 (95% CI: 2.07-7.88, p < 0.0001)] and ASCVD risk score [OR = 2.85 (95% CI: 1.19-6.83, p = 0.018)], respectively. CONCLUSION Higher liver fat content increases CVD risk independently of age, gender, ethnicity and BMI. These findings raise the question whether liver fat quantification should be incorporated into risk calculators to further stratify those with higher CVD risk.
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Affiliation(s)
- Selena Z. Kuo
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
- Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Sandra Cepin
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Jaclyn Bergstrom
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Harris Siddiqi
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Jinho Jung
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Scarlett Lopez
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Daniel Q. Huang
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Pam Taub
- Division of Cardiovascular Medicine, Department of Medicine, University of California at San Diego, La Jolla, California, USA
| | - Maral Amangurbanova
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
- Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA
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Bischoff SC, Ockenga J, Eshraghian A, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. Practical guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2023; 42:987-1024. [PMID: 37146466 DOI: 10.1016/j.clnu.2023.03.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 05/07/2023]
Abstract
BACKGROUND Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases. METHODS The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text. RESULTS In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; and Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim gGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Cho Y, Park HS, Huh BW, Lee YH, Seo SH, Seo DH, Ahn SH, Hong S, Kim SH. Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus. Diabetes Metab J 2023; 47:232-241. [PMID: 36653888 PMCID: PMC10040622 DOI: 10.4093/dmj.2021.0355] [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: 12/15/2021] [Accepted: 03/18/2022] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. RESULTS Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. CONCLUSION NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.
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Affiliation(s)
- Yongin Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Hye-Sun Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Wook Huh
- Huh’s Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea
| | - Yong-ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seong Ha Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Da Hea Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seong Hee Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Seongbin Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
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Chew NW, Muthiah MD, Sanyal AJ. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: pathophysiology and implications for cardiovascular disease. CARDIOVASCULAR ENDOCRINOLOGY AND METABOLISM 2023:137-173. [DOI: 10.1016/b978-0-323-99991-5.00003-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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17
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Bischoff SC, Barazzoni R, Busetto L, Campmans‐Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon‐Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint European Society for Clinical Nutrition and Metabolism / United European Gastroenterology guideline. United European Gastroenterol J 2022; 10:663-720. [PMID: 35959597 PMCID: PMC9486502 DOI: 10.1002/ueg2.12280] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for European Society for Clinical Nutrition and Metabolism guidelines, following the Scottish Intercollegiate Guidelines Network grading system (A, B, 0, and good practice point [GPP]). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational SciencesUniversity of TriesteTriesteItaly
| | - Luca Busetto
- Department of MedicineUniversity of PadovaPadovaItaly
| | - Marjo Campmans‐Kuijpers
- Department of Gastroenterology and HepatologyUniversity Medical Centre GroningenGroningenThe Netherlands
| | - Vincenzo Cardinale
- Department of Medico‐Surgical Sciences and BiotechnologiesSapienza University of RomeRomeItaly
| | - Irit Chermesh
- Department of GastroenterologyRambam Health Care CampusAffiliated with Technion‐Israel Institute of TechnologyHaifaIsrael
| | - Ahad Eshraghian
- Department of Gastroenterology and HepatologyAvicenna HospitalShirazIran
| | - Haluk Tarik Kani
- Department of GastroenterologyMarmara UniversitySchool of MedicineIstanbulTurkey
| | - Wafaa Khannoussi
- Hepato‐Gastroenterology DepartmentMohammed VI University HospitalOujdaMorocco
- Laboratoire de Recherche des Maladies Digestives (LARMAD)Mohammed the First UniversityOujdaMorocco
| | - Laurence Lacaze
- Department of NutritionRennes HospitalRennesFrance
- Department of general surgeryMantes‐la‐Jolie HospitalFrance
- Department of clinical nutritionPaul Brousse‐Hospital, VillejuifFrance
| | - Miguel Léon‐Sanz
- Department of Endocrinology and NutritionUniversity Hospital Doce de OctubreMedical SchoolUniversity ComplutenseMadridSpain
| | - Juan M. Mendive
- La Mina Primary Care Academic Health Centre. Catalan Institute of Health (ICS)University of BarcelonaBarcelonaSpain
| | - Michael W. Müller
- Department of General and Visceral SurgeryRegionale Kliniken HoldingKliniken Ludwigsburg‐Bietigheim gGmbHBietigheim‐BissingenGermany
| | - Johann Ockenga
- Medizinische Klinik IIKlinikum Bremen‐MitteBremenGermany
| | - Frank Tacke
- Department of Hepatology & GastroenterologyCharité Universitätsmedizin BerlinCampus Virchow‐Klinikum and Campus Charité MitteBerlinGermany
| | - Anders Thorell
- Department of Clinical ScienceDanderyds HospitalKarolinska InstitutetStockholmSweden
- Department of SurgeryErsta HospitalStockholmSweden
| | - Darija Vranesic Bender
- Department of Internal MedicineUnit of Clinical NutritionUniversity Hospital Centre ZagrebZagrebCroatia
| | - Arved Weimann
- Department of General, Visceral and Oncological SurgerySt. George HospitalLeipzigGermany
| | - Cristina Cuerda
- Departamento de MedicinaUniversidad Complutense de MadridNutrition UnitHospital General Universitario Gregorio MarañónMadridSpain
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Ferraioli G, Raimondi A, Maiocchi L, De Silvestri A, Filice C. Quantification of Liver Fat Content with the iATT Algorithm: Correlation with Controlled Attenuation Parameter. Diagnostics (Basel) 2022; 12:1787. [PMID: 35892497 PMCID: PMC9394249 DOI: 10.3390/diagnostics12081787] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 11/17/2022] Open
Abstract
Background: The primary aim of our study was to assess the correlation between an improved version of the attenuation coefficient available on the Arietta 850 ultrasound system (iATT, Fujifilm Healthcare, Tokyo, Japan) and controlled attenuation parameter (CAP). The secondary aim was to assess whether focusing only on iATT acquisition without following the strict protocol for liver stiffness measurements would affect iATT measurement. Methods: Consecutive individuals were enrolled. Pearson’s r was used to test the correlation between ATT and CAP values. The concordance between iATT and CAP was tested using Lin’s concordance correlation coefficient (CCC). Results: 354 individuals (203 males, 151 females) were studied. The overall Pearson correlation between CAP and iATT values obtained following or not following the liver stiffness measurement protocol, respectively, were r = 0.73 and r = 0.71. The correlation was affected by the interquartile range/median (IQR/M) of the 10 measurements: it was r = 0.75 for IQR/M ≤ 15% and r = 0.60 for IQR/M > 15%. CCC showed that there was a moderate to good concordance between iATT and CAP values. Conclusion: iATT shows a strong correlation with CAP that does not decrease when the protocol for liver stiffness acquisition is not followed. The correlation between iATT and CAP values is higher when the IQR/M ≤ 15%.
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Affiliation(s)
- Giovanna Ferraioli
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Università di Pavia, Viale Brambilla 74, 27100 Pavia, Italy; (A.R.); (C.F.)
| | - Ambra Raimondi
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Università di Pavia, Viale Brambilla 74, 27100 Pavia, Italy; (A.R.); (C.F.)
- Dipartimento di Scienze Mediche e Malattie Infettive, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy;
| | - Laura Maiocchi
- Dipartimento di Scienze Mediche e Malattie Infettive, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy;
| | - Annalisa De Silvestri
- Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy;
| | - Carlo Filice
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Università di Pavia, Viale Brambilla 74, 27100 Pavia, Italy; (A.R.); (C.F.)
- Dipartimento di Scienze Mediche e Malattie Infettive, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy;
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Treatment Candidacy for Pharmacologic Therapies for NASH. Clin Gastroenterol Hepatol 2022; 20:1209-1217. [PMID: 33711479 PMCID: PMC8908435 DOI: 10.1016/j.cgh.2021.03.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 02/24/2021] [Accepted: 03/03/2021] [Indexed: 02/07/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) has emerged as one of the important causes of cirrhosis and hepatocellular carcinoma, and over 50 therapeutic agents are in various phases of clinical development. Recently, obeticholic acid has achieved the interim histological endpoint of fibrosis improvement with no worsening of NASH in the phase 3 REGENERATE study, and now patients are being followed for long-term clinical outcomes. Several drugs are in Phase 3 trials with a goal to achieve conditional registration under the subpart H pathway by the United States Food and Drug Administration (FDA). It is thus timely to consider the current situation and the way ahead in the management of NASH. In this article, we review the natural history of nonalcoholic fatty liver disease, upcoming treatments for NASH and various assessments. Based on the current knowledge, we discuss what should be the target treatment population and whether noninvasive tests are ready to guide NASH treatments both for patient selection and evaluation of treatment response.
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Park J, Lee JM, Lee G, Jeon SK, Joo I. Quantitative Evaluation of Hepatic Steatosis Using Advanced Imaging Techniques: Focusing on New Quantitative Ultrasound Techniques. Korean J Radiol 2022; 23:13-29. [PMID: 34983091 PMCID: PMC8743150 DOI: 10.3348/kjr.2021.0112] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 07/26/2021] [Accepted: 08/31/2021] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease, characterized by excessive accumulation of fat in the liver, is the most common chronic liver disease worldwide. The current standard for the detection of hepatic steatosis is liver biopsy; however, it is limited by invasiveness and sampling errors. Accordingly, MR spectroscopy and proton density fat fraction obtained with MRI have been accepted as non-invasive modalities for quantifying hepatic steatosis. Recently, various quantitative ultrasonography techniques have been developed and validated for the quantification of hepatic steatosis. These techniques measure various acoustic parameters, including attenuation coefficient, backscatter coefficient and speckle statistics, speed of sound, and shear wave elastography metrics. In this article, we introduce several representative quantitative ultrasonography techniques and their diagnostic value for the detection of hepatic steatosis.
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Affiliation(s)
- Junghoan Park
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.
| | - Gunwoo Lee
- Ultrasound R&D 2 Group, Health & Medical Equipment Business, Samsung Electronics Co., Ltd., Seoul, Korea
| | - Sun Kyung Jeon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
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22
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Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives. Biomolecules 2021; 12:biom12010056. [PMID: 35053205 PMCID: PMC8774162 DOI: 10.3390/biom12010056] [Citation(s) in RCA: 159] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/24/2021] [Accepted: 12/30/2021] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors—genetic, metabolic, and dietary—intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.
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The most appropriate region-of-interest position for attenuation coefficient measurement in the evaluation of liver steatosis. J Med Ultrason (2001) 2021; 48:615-621. [PMID: 34453648 DOI: 10.1007/s10396-021-01124-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Attenuation imaging (ATI) is a new noninvasive ultrasound technique for assessing steatosis grade (S). However, validated region-of-interest (ROI) sampling strategies are not currently available. We investigated the diagnostic performance of various ATI-ROI positions for determining histopathologic S in patients with nonalcoholic fatty liver disease (NAFLD). METHODS This retrospective study included 105 patients with biopsy-proven NAFLD. All attenuation coefficient (AC, dB/cm/MHz) measurements were obtained by the same hepatologist using a commercially available ultrasound system on the same day as liver biopsy. Mean (± standard deviation) age and body mass index of the patients were 53 (± 18) years and 27.1 (± 4.1) kg/m2, respectively. The numbers of patients with steatosis affecting < 5%, 5-33%, 33-66%, and > 66% of hepatocytes were 8, 50, 29, and 18, respectively. The ATI-ROI was placed at three different positions for AC measurement using a dedicated workstation: the upper edge of the area ROI, twice the depth of the liver capsule, and the lower edge of the area ROI. Diagnostic performance was evaluated using the area under the receiver-operating characteristic curve (AUC). RESULTS The AUCs of AC at the three ATI-ROI positions were 0.734 (95% confidence interval [CI]: 0.470-0.998), 0.750 (0.639-0.861), and 0.878 (0.788-0.968) for S ≥ 1; 0.503 (0.392-0.615), 0.824 (0.741-0.907), and 0.809 (0.724-0.895) for S ≥ 2; and 0.606 (0.486-0.726), 0.849 (0.767-0.932), and 0.737 (0.626-0.848) for S = 3, respectively. CONCLUSION For accurate steatosis grade assessment, the ATI-ROI should not be placed at the upper edge of the area ROI.
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Ferraioli G, Maiocchi L, Savietto G, Tinelli C, Nichetti M, Rondanelli M, Calliada F, Preda L, Filice C. Performance of the Attenuation Imaging Technology in the Detection of Liver Steatosis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:1325-1332. [PMID: 32960457 PMCID: PMC8246860 DOI: 10.1002/jum.15512] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/01/2020] [Accepted: 09/03/2020] [Indexed: 05/12/2023]
Abstract
OBJECTIVES The main aim was to assess the performance and cutoff value for the detection of liver steatosis (grade S > 0) with the Attenuation Imaging-Penetration (ATI-Pen) algorithm available on the Aplio i-series ultrasound systems (Canon Medical Systems, Otawara, Japan). The magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) was used as the reference standard. Secondary aims were to compare the results to those obtained with the previous ATI algorithm (Attenuation Imaging-General [ATI-Gen]) and with the controlled attenuation parameter (CAP) and to generate a regression equation between ATI-Pen and ATI-Gen values. METHODS Consecutive adult patients potentially at risk of liver steatosis were prospectively enrolled. Each patient underwent ultrasound quantification of liver steatosis with ATI-Pen and ATI-Gen and a CAP assessment with the FibroScan system (Echosens, Paris, France). The MRI-PDFF evaluation was performed within a week. The correlations between ATI-Pen, ATI-Gen, the CAP, and the MRI-PDFF were analyzed with the Pearson rank correlation coefficient. The diagnostic performance of ATI-Pen, ATI-Gen, and the CAP was assessed with receiver operating characteristic curves and an area under the receiver operating characteristic curve (AUROC) analysis. RESULTS Seventy-two individuals (31 male and 41 female) were enrolled. Correlation coefficients of ATI-Pen, ATI-Gen, and the CAP with the MRI-PDFF were 0.78, 0.83, and 0.58, respectively. The AUROCs of ATI-Pen, ATI-Gen, and the CAP for detecting steatosis (S > 0) were 0.90 (95% confidence interval, 0.81-0.96), 0.92 (0.82-0.98), and 0.85 (0.74-0.92), and the cutoffs were greater than 0.69 dB/cm/MHz, greater than 0.62 dB/cm/MHz, and greater than 273 dB/m. The regression equation between ATI-Pen and ATI-Gen was ATI-Pen = 0.88 ATI-Gen + 0.13. CONCLUSIONS Attenuation Imaging is a reliable tool for detecting liver steatosis, showing an excellent correlation with the MRI-PDFF and high performance with AUROCs of 0.90 or higher.
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Affiliation(s)
- Giovanna Ferraioli
- Department of Clinical, Surgical, Diagnostic, and Pediatric SciencesUniversity of PaviaPaviaItaly
| | - Laura Maiocchi
- Department of Clinical Sciences and Infectious DiseasesFondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San MatteoPaviaItaly
| | - Giovanni Savietto
- Department of RadiologyFondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San MatteoPaviaItaly
| | - Carmine Tinelli
- Department of Clinical Epidemiology and Biometric UnitFondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San MatteoPaviaItaly
| | - Mara Nichetti
- Department of Applied Health SciencesAzienda di Servizi Alla Persona di PaviaPaviaItaly
| | - Mariangela Rondanelli
- Department of Public HealthUniversity of PaviaPaviaItaly
- Istituto di Ricovero e Cura a Carattere Scientifico Mondino FoundationPaviaItaly
| | - Fabrizio Calliada
- Department of Clinical, Surgical, Diagnostic, and Pediatric SciencesUniversity of PaviaPaviaItaly
| | - Lorenzo Preda
- Department of Clinical, Surgical, Diagnostic, and Pediatric SciencesUniversity of PaviaPaviaItaly
- Department of RadiologyFondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San MatteoPaviaItaly
| | - Carlo Filice
- Department of Clinical, Surgical, Diagnostic, and Pediatric SciencesUniversity of PaviaPaviaItaly
- Department of Clinical Sciences and Infectious DiseasesFondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San MatteoPaviaItaly
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Abstract
TGR5 (G protein-coupled bile acid receptor 1, GPBAR-1) is a G protein-coupled receptor with seven transmembrane domains and is widely distributed in various organs and tissues. As an important bile acid receptor, TGR5 can be activated by primary and secondary bile acids. Increased expression of TGR5 is a risk factor for polycystic liver disease and hepatobiliary cancer. However, there is evidence that the anti-inflammatory effect of the TGR5 receptor and its regulatory effect on hydrophobic bile acid confer protective effects against most liver diseases. Recent studies have shown that TGR5 receptor activation can alleviate the development of diabetic liver fibrosis, regulate the differentiation of natural killer T cells into NKT10 cells, increase the secretion of anti-inflammatory factors, inhibit the invasion of hepatitis B virus, promote white adipose tissue browning, improve arterial vascular dynamics, maintain tight junctions between bile duct cells, and protect against apoptosis. In portal hypertension, TGR5 receptor activation can inhibit the contraction of hepatic stellate cells and improve intrahepatic microcirculation. In addition, the discovery of the regulatory relationship between the TGR5 receptor and miRNA-26a provides a new direction for further studies of the molecular mechanism underlying the effects of TGR5. In this review, we describe recent findings linking TGR5 to various liver diseases, with a focus on the mechanisms underlying its effects and potential therapeutic implications.
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Affiliation(s)
- Ke Ma
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Dan Tang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Chang Yu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lijin Zhao
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States and increasing globally. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), can lead to cirrhosis and complications of end-stage liver disease. No FDA-approved therapy for NAFLD/NASH exists. Treatment of NAFLD/NASH includes effective and sustained life-style modification and weight loss. This review reports on the recent findings of bariatric surgery in the management of NASH. RECENT FINDINGS NAFLD, at all stages, is common in those who meet indication for bariatric surgery. Bariatric surgery resolves NAFLD/NASH and reverses early stages of fibrosis. Although randomized controlled trials of bariatric surgery in NASH are infeasible, studies defining the metabolic changes induced by bariatric surgery, and their effect on NASH, provide insight for plausible pharmacologic targets for the nonsurgical treatment of NASH. SUMMARY Resolution of NASH and fibrosis regression can occur after bariatric surgery. Although the exact mechanism(s) underlying the improvement of NASH and hepatic fibrosis following bariatric surgery is not fully elucidated, emerging data on this topic is vitally important for lending insight into the pharmacotherapies for NASH for patients who are not otherwise suitable candidates for bariatric surgery.
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Petroff D, Blank V, Newsome PN, Shalimar, Voican CS, Thiele M, de Lédinghen V, Baumeler S, Chan WK, Perlemuter G, Cardoso AC, Aggarwal S, Sasso M, Eddowes PJ, Allison M, Tsochatzis E, Anstee QM, Sheridan D, Cobbold JF, Naveau S, Lupsor-Platon M, Mueller S, Krag A, Irles-Depe M, Semela D, Wong GLH, Wong VWS, Villela-Nogueira CA, Garg H, Chazouillères O, Wiegand J, Karlas T. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis. Lancet Gastroenterol Hepatol 2021; 6:185-198. [PMID: 33460567 DOI: 10.1016/s2468-1253(20)30357-5] [Citation(s) in RCA: 162] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/13/2020] [Accepted: 10/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. METHODS We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. FINDINGS 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. INTERPRETATION CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. FUNDING The German Federal Ministry of Education and Research and Echosens.
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Affiliation(s)
- David Petroff
- Clinical Trial Centre, University of Leipzig, Leipzig, Germany; Faculty of Medicine, Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany
| | - Valentin Blank
- Faculty of Medicine, Integrated Research and Treatment Center AdiposityDiseases, University of Leipzig, Leipzig, Germany; Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Philip N Newsome
- National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK; Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Cosmin Sebastian Voican
- Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, DHU Hepatinov, Labex LERMIT, Clamart, France
| | - Maja Thiele
- Department of Gastroenterology and Hepatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Victor de Lédinghen
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France; INSERM U1053, Bordeaux University, Bordeaux, France
| | - Stephan Baumeler
- Department of Gastroenterology and Hepatology, Cantonal Hospital St Gallen, St Gallen, Switzerland
| | - Wah Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Gabriel Perlemuter
- Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, DHU Hepatinov, Labex LERMIT, Clamart, France
| | - Ana-Carolina Cardoso
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sandeep Aggarwal
- Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
| | - Magali Sasso
- Research and Development Department, Echosens, Paris, France
| | - Peter J Eddowes
- National Institute for Health Research, Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK; Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK; University of Nottingham, Nottingham, UK
| | - Michael Allison
- Liver Unit, Addenbrooke's Hospital, Cambridge Biomedical Research Centre, Cambridge, UK
| | - Emmanuel Tsochatzis
- University College London Institute for Liver and Digestive Health, Royal Free Hospital, London, UK
| | - Quentin M Anstee
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle National Institute for Health Research Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - David Sheridan
- Institute of Translational and Stratified Medicine, Faculty of Medicine and Dentistry, University of Plymouth, Plymouth, UK
| | - Jeremy F Cobbold
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
| | - Sylvie Naveau
- Faculté de Médecine Paris-Sud, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; Service d'Hépato-Gastroentérologie et Nutrition, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, DHU Hepatinov, Labex LERMIT, Clamart, France
| | - Monica Lupsor-Platon
- Department of Medical Imaging, Iuliu Hatieganu University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania
| | - Sebastian Mueller
- Department of Medicine and Liver Diseases, Salem Medical Center, University of Heidelberg, Heidelberg, Germany
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Marie Irles-Depe
- Centre d'Investigation de la Fibrose Hépatique, Bordeaux University Hospital, Pessac, France; INSERM U1053, Bordeaux University, Bordeaux, France
| | - David Semela
- Department of Gastroenterology and Hepatology, Cantonal Hospital St Gallen, St Gallen, Switzerland
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Sha Tin, Hong Kong; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Cristiane A Villela-Nogueira
- Hepatology Unit, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Harshit Garg
- Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
| | - Olivier Chazouillères
- Hepatology Department, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Centre de Recherche Saint-Antoine, Sorbonne University, Paris, France
| | - Johannes Wiegand
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
| | - Thomas Karlas
- Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
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Plaza-Díaz J, Solis-Urra P, Aragón-Vela J, Rodríguez-Rodríguez F, Olivares-Arancibia J, Álvarez-Mercado AI. Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis. Biomedicines 2021; 9:145. [PMID: 33546191 PMCID: PMC7913217 DOI: 10.3390/biomedicines9020145] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/26/2021] [Accepted: 01/31/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).
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Affiliation(s)
- Julio Plaza-Díaz
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada;
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Patricio Solis-Urra
- Faculty of Education and Social Sciences, Universidad Andres Bello, Viña del Mar 2531015, Chile;
| | - Jerónimo Aragón-Vela
- Department of Nutrition, Exercise, and Sport (NEXS), University of Copenhagen, DK-2200 Copenhagen, Denmark
| | - Fernando Rodríguez-Rodríguez
- IRyS Research Group, School of Physical Education, Pontificia Universidad Católica de Valparaíso, Valparaíso 2374631, Chile; (F.R.-R.); (J.O.-A.)
| | - Jorge Olivares-Arancibia
- IRyS Research Group, School of Physical Education, Pontificia Universidad Católica de Valparaíso, Valparaíso 2374631, Chile; (F.R.-R.); (J.O.-A.)
- Grupo AFySE, Investigación en Actividad Física y Salud Escolar, Escuela de Pedagogía en Educación Física, Facultad de Educación, Universidad de las Américas, Santiago 8370035, Chile
| | - Ana I. Álvarez-Mercado
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, 18016 Granada, Spain
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Xiao F, Shi X, Huang P, Zeng X, Wang L, Zeng J, Liu C, Yan B, Song H, Xu Y, Han L, Zhao Q, Lin M, Li X. Dose-response relationship between serum fibroblast growth factor 21 and liver fat content in non-alcoholic fatty liver disease. DIABETES & METABOLISM 2020; 47:101221. [PMID: 33373666 DOI: 10.1016/j.diabet.2020.101221] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 12/03/2020] [Accepted: 12/06/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND & AIM Although serum fibroblast growth factor 21 (FGF21) levels are associated with liver fat content in non-alcoholic liver fat disease (NAFLD), the precise nature of the association remains undetermined. Therefore, this study aimed to explore the potential dose-response relationship between FGF21 and liver fat content in NAFLD. METHODS For this exploratory study from a randomized trial, 220 NAFLD patients with central obesity were recruited via community-based screening and randomly assigned to either control, moderate or vigorous-moderate exercise groups for 12 months. After this exercise intervention, patients were followed-up for a further 12 months. Serum FGF21 levels were measured by ELISA. Intrahepatic triglyceride (IHTG) content was determined by proton magnetic resonance spectroscopy. RESULTS Of the 220 patients, 149 (67.7%) were female; mean age was 53.9 ± 7.1 years and mean BMI was 28.0 ± 2.9 kg/m2 for all patients. Baseline IHGT increased gradually (P = 0.029 for trend) according to baseline serum FGF21 quartiles 1, 2, 3 and 4 (212.3, 358.9, 538.7 and 793.5 pg/mL, respectively). On grouping the distribution of serum FGF21 level changes into quartiles at month 12, the relative IHTG loss increased as serum FGF21 levels were reduced (P = 0.004 for trend). A similar trend was observed at month 24 (P = 0.006 for trend). Multivariate linear regression analysis revealed that changes in serum FGF21 levels were independently associated with changes in IHTG at both month 12 [β (SE), 0.136 (0.118); P = 0.048] and month 24 [β (SE), 0.152 (0.139); P = 0.041]. Using restricted cubic spline regression, changes in serum FGF21 were strongly and positively associated with their corresponding relative IHTG loss at both month 12 and follow-up (Poverall = 0.017, Pnon-linear = 0.044 and Poverall = 0.020, Pnon-linear = 0.361, respectively, for dose-response). CONCLUSION Serum FGF21 is strongly associated with liver fat content in a dose-response manner in centrally obese NAFLD patients. These findings support the use of serum FGF21 as a biomarker of liver fat content in NAFLD.
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Affiliation(s)
- F Xiao
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - X Shi
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - P Huang
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - X Zeng
- Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; Xiamen Diabetes Institute, Xiamen, China
| | - L Wang
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China
| | - J Zeng
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China
| | - C Liu
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China
| | - B Yan
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Xiamen Diabetes Institute, Xiamen, China
| | - H Song
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China
| | - Y Xu
- School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - L Han
- School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Q Zhao
- School of Medicine, Xiamen University, Xiamen, China
| | - M Lin
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; Xiamen Diabetes Institute, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
| | - X Li
- Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; Xiamen Diabetes Institute, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
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Grąt K, Grąt M, Rowiński O. Usefulness of Different Imaging Modalities in Evaluation of Patients with Non-Alcoholic Fatty Liver Disease. Biomedicines 2020; 8:298. [PMID: 32839409 PMCID: PMC7556032 DOI: 10.3390/biomedicines8090298] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/13/2020] [Accepted: 08/19/2020] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are becoming some of the major health problems in well-developed countries, together with the increasing prevalence of obesity, metabolic syndrome, and all of their systemic complications. As the future prognoses are even more disturbing and point toward further increase in population affected with NAFLD/NASH, there is an urgent need for widely available and reliable diagnostic methods. Consensus on a non-invasive, accurate diagnostic modality for the use in ongoing clinical trials is also required, particularly considering a current lack of any registered drug for the treatment of NAFLD/NASH. The aim of this narrative review was to present current information on methods used to assess liver steatosis and fibrosis. There are several imaging modalities for the assessment of hepatic steatosis ranging from simple density analysis by computed tomography or conventional B-mode ultrasound to magnetic resonance spectroscopy (MRS), magnetic resonance imaging proton density fat fraction (MRI-PDFF) or controlled attenuation parameter (CAP). Fibrosis stage can be assessed by magnetic resonance elastography (MRE) or different ultrasound-based techniques: transient elastography (TE), shear-wave elastography (SWE) and acoustic radiation force impulse (ARFI). Although all of these methods have been validated against liver biopsy as the reference standard and provided good accuracy, the MRS and MRI-PDFF currently outperform other methods in terms of diagnosis of steatosis, and MRE in terms of evaluation of fibrosis.
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Affiliation(s)
- Karolina Grąt
- Second Department of Clinical Radiology, Medical University of Warsaw, 02-097 Warsaw, Poland;
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland;
| | - Olgierd Rowiński
- Second Department of Clinical Radiology, Medical University of Warsaw, 02-097 Warsaw, Poland;
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Keramida G, Peters AM. FDG PET/CT of the non‐malignant liver in an increasingly obese world population. Clin Physiol Funct Imaging 2020; 40:304-319. [DOI: 10.1111/cpf.12651] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 05/11/2020] [Accepted: 06/04/2020] [Indexed: 12/19/2022]
Affiliation(s)
- Georgia Keramida
- Department of Nuclear Medicine Royal Brompton and HarefieldNHS Foundation Trust London UK
| | - A. Michael Peters
- Department of Nuclear Medicine King’s College HospitalNHS Foundation Trusts London UK
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Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, Kayali Z, Wong VWS, Greenbloom S, Jayakumar S, Shiffman ML, Freilich B, Lawitz EJ, Gane EJ, Harting E, Xu J, Billin AN, Chung C, Djedjos CS, Subramanian GM, Myers RP, Middleton MS, Rinella M, Noureddin M. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology 2020; 72:58-71. [PMID: 32115759 DOI: 10.1002/hep.31205] [Citation(s) in RCA: 254] [Impact Index Per Article: 50.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 01/06/2020] [Accepted: 02/12/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS We evaluated the safety and efficacy of cilofexor (formerly GS-9674), a small-molecule nonsteroidal agonist of farnesoid X receptor, in patients with nonalcoholic steatohepatitis (NASH). APPROACH AND RESULTS In this double-blind, placebo-controlled, phase 2 trial, 140 patients with noncirrhotic NASH, diagnosed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥8% and liver stiffness ≥2.5 kPa by magnetic resonance elastography (MRE) or historical liver biopsy, were randomized to receive cilofexor 100 mg (n = 56), 30 mg (n = 56), or placebo (n = 28) orally once daily for 24 weeks. MRI-PDFF, liver stiffness by MRE and transient elastography, and serum markers of fibrosis were measured at baseline and week 24. At baseline, median MRI-PDFF was 16.3% and MRE-stiffness was 3.27 kPa. At week 24, patients receiving cilofexor 100 mg had a median relative decrease in MRI-PDFF of -22.7%, compared with an increase of 1.9% in those receiving placebo (P = 0.003); the 30-mg group had a relative decrease of -1.8% (P = 0.17 vs. placebo). Declines in MRI-PDFF of ≥30% were experienced by 39% of patients receiving cilofexor 100 mg (P = 0.011 vs. placebo), 14% of those receiving cilofexor 30 mg (P = 0.87 vs. placebo), and 13% of those receiving placebo. Serum gamma-glutamyltransferase, C4, and primary bile acids decreased significantly at week 24 in both cilofexor treatment groups, whereas significant changes in Enhanced Liver Fibrosis scores and liver stiffness were not observed. Cilofexor was generally well-tolerated. Moderate to severe pruritus was more common in patients receiving cilofexor 100 mg (14%) than in those receiving cilofexor 30 mg (4%) and placebo (4%). CONCLUSIONS Cilofexor for 24 weeks was well-tolerated and provided significant reductions in hepatic steatosis, liver biochemistry, and serum bile acids in patients with NASH. ClinicalTrials.gov No. NCT02854605.
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Affiliation(s)
| | | | | | | | | | | | | | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | | | | | | | | | - Eric J Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX
| | - Edward J Gane
- Liver Unit, Auckland City Hospital, Auckland, New Zealand
| | | | - Jun Xu
- Gilead Sciences, Inc., Foster City, CA
| | | | | | | | | | | | | | - Mary Rinella
- Feinberg School of Medicine, Northwestern University, Chicago, IL
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Chen J, Duan S, Ma J, Wang R, Chen J, Liu X, Xue L, Xie S, Yao S. MRI-determined liver fat correlates with risk of metabolic syndrome in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2020; 32:754-761. [PMID: 32091437 DOI: 10.1097/meg.0000000000001688] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Little is known about that the relationship between hepatic fat content (HFC) and metabolic syndrome (MetS). We aimed to determine whether HFC correlated with MetS in patients with nonalcoholic fatty liver disease (NAFLD). METHODS HFC was measured by MRI-determined proton density fat fraction (MRI-PDFF) for 131 suspected NAFLD subjects. Patients with NAFLD defined as MRI-PDFF ≥5% were stratified into two groups based on whether they were above or below the median MRI-PDFF value; the MRI-PDFF value for the control group was <5%. The primary outcome was the presence of MetS. Logistic regression models were used to obtain the associations between the severity of liver fat and MetS, and the corresponding odds ratios (ORs) and 95% confidence intervals (CIs) were recorded. RESULTS Compared to NAFLD patients with low-HFC (n = 48) and the control group (n = 35), NAFLD patients with high-HFC (n = 48) had significantly greater prevalence of central obesity, hypertension, hyperglycemia, and hypertriglyceridemia (all P < 0.05). NAFLD patients with high-HFC had a higher prevalence of MetS than NAFLD patients with low-HFC (79.2% vs. 56.2%, P < 0.05). The multivariate-adjusted OR for the prevalence of MetS comparing NAFLD patient with low-HFC and high-HFC to the control group were 4.56 (95% CI: 0.54-38.79, P = 0.165) and 22.91 (95% CI: 1.80-292.21, P = 0.016), respectively (Ptrend = 0.014). CONCLUSION Increased hepatic fat quantitatively measured by MRI-PDFF had a significant dose-relationship with the presence of MetS, and the amount of liver fat may affect cardiovascular risk.
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Affiliation(s)
- Jialiang Chen
- Graduate School, Beijing University of Chinese Medicine
| | - Shaojie Duan
- Graduate School, Beijing University of Chinese Medicine
| | - Jie Ma
- Graduate School, Beijing University of Chinese Medicine
| | - Rongrui Wang
- Graduate School, Beijing University of Chinese Medicine
| | - Jie Chen
- Graduate School, Beijing University of Chinese Medicine
| | - Xinyuan Liu
- Graduate School, Beijing University of Chinese Medicine
| | - Lijun Xue
- School of Biological Science and Medical Engineering, Beihang University
| | - Sheng Xie
- Department of Radiology, China-Japan Friendship Hospital
| | - Shukun Yao
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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Saki S, Saki N, Poustchi H, Malekzadeh R. Assessment of Genetic Aspects of Non-alcoholic Fatty Liver and Premature Cardiovascular Events. Middle East J Dig Dis 2020; 12:65-88. [PMID: 32626560 PMCID: PMC7320986 DOI: 10.34172/mejdd.2020.166] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Recent evidence has demonstrated a strong interplay and multifaceted relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). CVD is the major cause of death in patients with NAFLD. NAFLD also has strong associations with diabetes and metabolic syndrome. In this comprehensive review, we aimed to overview the primary environmental and genetic risk factors of NAFLD, and CVD and also focus on the genetic aspects of these two disorders. NAFLD and CVD are both heterogeneous diseases with common genetic and molecular pathways. We have searched for the latest published articles regarding this matter and tried to provide an overview of recent insights into the genetic aspects of NAFLD and CVD. The common genetic and molecular pathways involved in NAFLD and CVD are insulin resistance (IR), subclinical inflammation, oxidative stress, and atherogenic dyslipidemia. According to an investigation, the exact associations between genomic characteristics of NAFLD and CVD and casual relationships are not fully determined. Different gene polymorphisms have been identified as the genetic components of the NAFLDCVD association. Some of the most documented ones of these gene polymorphisms are patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), adiponectin-encoding gene (ADIPOQ), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), leptin receptor (LEPR), sterol regulatory element-binding proteins (SREBP), tumor necrosis factor-alpha (TNF-α), microsomal triglyceride transfer protein (MTTP), manganese superoxide dismutase (MnSOD), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), and mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain. Further cohort studies with a significant sample size using advanced genomic assessments and next-generation sequencing techniques are needed to shed more light on genetic associations between NAFLD and CVD.
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Affiliation(s)
- Sara Saki
- Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Saki
- Hoveizeh Cohort Study, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Poustchi
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Abstract
Non-alcoholic fatty liver disease (NAFLD) went beyond the competence of a gastroenterologist and acquired the character of a multidisciplinary problem. NAFLD requires the attention of many professionals. A characteristic feature of NAFLD is the variety of concomitant diseases and pathological conditions with common pathophysiological mechanisms. This review summarizes and presents the data available in the modern literature on the association of NAFLD with cardiovascular diseases, type 2 diabetes mellitus, hypothyroidism, polycystic ovary syndrome, chronic kidney disease, colorectal cancer, obstructive sleep apnea, osteoporosis, psoriasis.
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Affiliation(s)
- M. A. Livzan
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - O. V. Gaus
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - N. A. Nikolaev
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
| | - T. S. Krolevetz
- Federal State Educational Establishment of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation
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Wattacheril J. Extrahepatic Manifestations of Nonalcoholic Fatty Liver Disease. Gastroenterol Clin North Am 2020; 49:141-149. [PMID: 32033760 DOI: 10.1016/j.gtc.2019.10.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents a global public health burden. NAFLD, while strongly associated with the metabolic syndrome, can occur independently from existing metabolic diseases. In addition to liver-related disease burden and mortality, significant extrahepatic disease outcomes coexist with NAFLD, including cardiovascular diseases, chronic kidney disease, and type 2 diabetes. Management of these comorbidities contributes to the overall public health burden of NAFLD. These extrahepatic manifestations require healthcare interventions that are vigilant in monitoring for progression of liver disease while simultaneously managing overall morbidity and mortality from other organ systems.
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Affiliation(s)
- Julia Wattacheril
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center - NY Presbyterian Hospital, 622 West 168th Street, PH 14-105D, New York, NY 10032, USA.
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Kempinska-Podhorodecka A, Wunsch E, Milkiewicz P, Stachowska E, Milkiewicz M. The Association between SOCS1-1656G>A Polymorphism, Insulin Resistance and Obesity in Nonalcoholic Fatty Liver Disease (NAFLD) Patients. J Clin Med 2019; 8:jcm8111912. [PMID: 31717271 PMCID: PMC6912432 DOI: 10.3390/jcm8111912] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 10/31/2019] [Accepted: 11/06/2019] [Indexed: 12/20/2022] Open
Abstract
Suppressor of cytokine signaling (SOCS) proteins prevent uncontrolled cytokine signaling and appear to play a role in the pathological processes behind obesity and insulin resistance. The polymorphism of the SOCS1 gene (rs243330, −1656G>A) is associated with obesity and glucose sensitivity. To estimate the effect of this SOCS1 gene polymorphism on nonalcoholic fatty liver disease (NAFLD) susceptibility, we performed a study on 138 patients with ultrasound-confirmed NAFLD and 1000 healthy blood donors. The relationship between the SOCS1−1656G>A polymorphism and serum biochemical parameters in NAFLD was additionally investigated. The SOCS1 variant was genotyped using a dedicated TaqMan assay. The frequency of rs243330 polymorphism did not differ between patients and controls. However, in a cohort of obese individuals (BMI ≥ 30 kg/m2) the occurrence of the G allele of the SOCS1−1656G>A polymorphism was strongly associated with NAFLD (odds ratio (OR) 1.6; 95% CI,1.1–2.5; p = 0.009), and carriers of the AA genotype have lower risk of developing NAFLD (OR 0.4; 95% CI, 0.2–0.7; p = 0.004). Overweight NAFLD patients who were carriers of GG genotypes had significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) values (p = 0.03 vs. AA), and the obese GG homozygotes had lower serum concertation of triglyceride (GG vs. AA; p = 0.02). Serum liver enzyme activities were not modified by the presence of SOCS1 risk variants. In conclusion, the observed phenotype of overweight NAFLD patients with non-elevated levels of TG and HOMA-IR, which is associated with genetic variants of SOCS1, provides a rationale for further research on the pathophysiology of fatty liver disease.
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Affiliation(s)
| | - Ewa Wunsch
- Translational Medicine Group, Pomeranian Medical University, 71-210 Szczecin, Poland; (E.W.); (P.M.)
| | - Piotr Milkiewicz
- Translational Medicine Group, Pomeranian Medical University, 71-210 Szczecin, Poland; (E.W.); (P.M.)
- Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland;
| | - Malgorzata Milkiewicz
- Department of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, Poland;
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Ferraioli G, Soares Monteiro LB. Ultrasound-based techniques for the diagnosis of liver steatosis. World J Gastroenterol 2019; 25:6053-6062. [PMID: 31686762 PMCID: PMC6824276 DOI: 10.3748/wjg.v25.i40.6053] [Citation(s) in RCA: 287] [Impact Index Per Article: 47.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 09/27/2019] [Accepted: 10/17/2019] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of diffuse liver disease. An accurate estimate of the fat in the liver is important in the diagnostic work-up of patients with NAFLD because the degree of liver steatosis is linked to the metabolic syndrome and the cardiovascular risk. Ultrasound (US) B-mode imaging allows to subjectively estimate the fatty infiltration in the liver; however, it has a low performance for the detection of mild steatosis. Quantitative US is based on the analysis of the radiofrequency echoes detected by an US system, and it allows to calculate a backscatter coefficient or an attenuation coefficient or the sound speed. The estimation of the backscatter coefficient is rather cumbersome and requires the use of a phantom for addressing all sources of variability. Controlled attenuation parameter (CAP) available on the FibroScan® system (Echosens, France) measures the attenuation of the US beam. CAP is accurate in grading fatty infiltration-even though there is an overlap between consecutive grade of liver steatosis-and the values are not influenced by liver fibrosis. Several US manufacturers are developing or have already developed software for quantifying the attenuation of the US beam. Preliminary results show that proprietary technologies implemented in US systems seem more accurate than CAP for grading liver steatosis. Another available method for quantifying liver steatosis is based on the computation of the sound speed and the initial results appear promising.
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Affiliation(s)
- Giovanna Ferraioli
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Medical School University of Pavia, Pavia 27100, Italy
- Clinical Sciences and Infectious Diseases Department, Fondazione IRCCS Policlinico S. Matteo, Pavia 27100, Italy
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Ferraioli G, Maiocchi L, Raciti MV, Tinelli C, De Silvestri A, Nichetti M, De Cata P, Rondanelli M, Chiovato L, Calliada F, Filice C. Detection of Liver Steatosis With a Novel Ultrasound-Based Technique: A Pilot Study Using MRI-Derived Proton Density Fat Fraction as the Gold Standard. Clin Transl Gastroenterol 2019; 10:e00081. [PMID: 31609745 PMCID: PMC6884349 DOI: 10.14309/ctg.0000000000000081] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Accepted: 08/05/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES The primary aim of this study was to investigate the value of attenuation imaging (ATI), a novel ultrasound technique for detection of steatosis, by comparing the results to that obtained with controlled attenuation parameter (CAP) and by using MRI-derived proton density fat fraction (PDFF) as reference standard. METHODS From March to November 2018, 114 consecutive adult subjects potentially at risk of steatosis and 15 healthy controls were enrolled. Each subject underwent ATI and CAP assessment on the same day. MRI-PDFF was performed within a week. RESULTS The prevalence of steatosis, as defined by MRI-PDFF ≥ 5%, was 70.7%. There was a high correlation of ATI with MRI-PDFF (r = 0.81, P < 0.0001). The correlation of CAP with MRI-PDFF and with ATI, respectively, was moderate (r = 0.65, P < 0.0001 and r = 0.61, P < 0.0001). The correlation of ATI or CAP with PDFF was not affected by age, gender, or body mass index. Area under the receiver operating characteristics of ATI and CAP, respectively, were 0.91 (0.84-0.95; P < 0.0001) and 0.85 (0.77-0.91; P < 0.0001) for detecting S > 0 steatosis (MRI-PDFF ≥ 5%); 0.95 (0.89-0.98; P < 0.0001) and 0.88 (0.81-0.93; P < 0.0001) for detecting S > 1 steatosis (MRI-PDFF ≥ 16.3%). The cutoffs of ATI and CAP, respectively, were 0.63 dB/cm/MHz and 258 dB/m for detecting S > 0 liver steatosis; 0.72 dB/cm/MHz and 304 dB/m for detecting S > 1 steatosis. ATI performed better than CAP, and this improvement was statistically significant for S > 1 (P = 0.04). DISCUSSION This study shows that, in patients with no fibrosis/mild fibrosis, ATI is a very promising tool for the noninvasive assessment of steatosis.
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Affiliation(s)
- Giovanna Ferraioli
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Medical School University of Pavia, Pavia, Italy
- Clinical Sciences and Infectious Diseases Department, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
| | - Laura Maiocchi
- Clinical Sciences and Infectious Diseases Department, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
| | - Maria Vittoria Raciti
- Department of Radiology, Fondazione IRCCS Policlinico S. Matteo, Medical School University of Pavia, Pavia, Italy
| | - Carmine Tinelli
- Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
| | - Annalisa De Silvestri
- Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
| | - Mara Nichetti
- Department of Applied Health Sciences, Azienda di Servizi alla Persona di Pavia, Medical School University of Pavia, Pavia, Italy
| | - Pasquale De Cata
- Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, University of Pavia, Pavia, Italy
| | - Mariangela Rondanelli
- Department of Applied Health Sciences, Azienda di Servizi alla Persona di Pavia, Medical School University of Pavia, Pavia, Italy
- Department of Public Health, Experimental and Forensic Medicine, IRCCS Mondino Foundation, Pavia, Italy
- Department of Public Health, Medical School University of Pavia, Pavia, Italy
| | - Luca Chiovato
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Medical School University of Pavia, Pavia, Italy
- Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, University of Pavia, Pavia, Italy
| | - Fabrizio Calliada
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Medical School University of Pavia, Pavia, Italy
- Department of Radiology, Fondazione IRCCS Policlinico S. Matteo, Medical School University of Pavia, Pavia, Italy
| | - Carlo Filice
- Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, Medical School University of Pavia, Pavia, Italy
- Clinical Sciences and Infectious Diseases Department, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
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Olubamwo OO, Virtanen JK, Pihlajamaki J, Mantyselka P, Tuomainen TP. Fatty liver index as a predictor of increased risk of cardiometabolic disease: finding from the Kuopio Ischaemic Heart Disease Risk Factor Study Cohort. BMJ Open 2019; 9:e031420. [PMID: 31492793 PMCID: PMC6731849 DOI: 10.1136/bmjopen-2019-031420] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Fatty liver disease (FLD), a global epidemic, is also a predictor of cardiometabolic disease (CMD) (type 2 diabetes or cardiovascular disease). Our objective was to examine whether progressive FLD, as assessed by fatty liver index (FLI), predicts increasing future CMD risk compared with relatively stable FLD, among middle-aged men. DESIGN Prospective epidemiological study. SETTING University affiliated research centre in Kuopio, Eastern Finland. PARTICIPANTS Our subjects were 501 men without CMD during the initial 4-year follow-up in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. OUTCOME MEASURE Over the initial 4-year follow-up, 135 men (26.9%) had a significant (≥10) FLI increase. The association of 4-year FLI increase with incident CMD was analysed in multivariable-adjusted Cox regression models, adjusting for baseline constitutional and lifestyle factors (model 1) and, in addition, metabolic and inflammation biomarker factors (model 2). RESULTS During a mean follow-up of 15 years, 301 new CMD cases occurred. We used subjects with low baseline FLI and no significant 4-year FLI increase as the reference. For subjects with intermediate baseline FLI and significant 4-year FLI increase, the HRs and 95% CIs for incident CMD in model 1 (2.13 (1.45 to 3.13)) and model 2 (1.73 (1.13 to 2.66)) exceeded values for subjects with similar baseline FLI without a significant 4-year change (HRs (95% CIs) were 1.36 (0.94 to 1.97) for model 1 and 1.18 (0.81 to 1.70) for model 2). They approached HRs (95% CI) for subjects who maintained high FLI over the 4 years (HRs (95% CIs) were 2.18 (1.54 to 3.10) in model 1 and 1.85 (1.21 to 2.82) in model 2). CONCLUSION Persons with significant FLI increase are likely with increasing CMD risk. Such persons should be evaluated for progressive FLD and CMD and managed to reduce CMD risk.
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Affiliation(s)
- Olubunmi O Olubamwo
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jyrki K Virtanen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Jussi Pihlajamaki
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
- Clinical Nutrition and Obesity Center, Kuopio University Hospital, KYS, Kuopio, Finland
| | - Pekka Mantyselka
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
- Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland
| | - Tomi-Pekka Tuomainen
- Institute of Public Health and Clinical Nutrition, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
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Ho CM, Ho SL, Jeng YM, Lai YS, Chen YH, Lu SC, Chen HL, Chang PY, Hu RH, Lee PH. Accumulation of free cholesterol and oxidized low-density lipoprotein is associated with portal inflammation and fibrosis in nonalcoholic fatty liver disease. JOURNAL OF INFLAMMATION-LONDON 2019; 16:7. [PMID: 30983887 PMCID: PMC6444889 DOI: 10.1186/s12950-019-0211-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 03/12/2019] [Indexed: 12/13/2022]
Abstract
Background Macrophages engulf oxidized-LDL (oxLDL) leading to accumulation of cellular cholesterol and formation of foam cells, which is a hallmark of atherosclerosis. Moreover, recent studies showed that accumulation of free cholesterol in macrophages leading to activation of NLRP3 inflammasome and production of interleukin-1β (IL-1β) has been linked to atherosclerosis-associated inflammation. However, it is not clear if cholesterol accumulation is associated with hepatic inflammation and fibrosis in the liver. In this study, we investigated the association of free cholesterol and oxLDL accumulation in portal vein with the inflammation, atherosclerosis, and fibrosis in human nonalcoholic fatty liver disease (NAFLD). Methods Serial sections derived from surgical specimens of NAFLD were stained with filipin and antibodies against IL-1β, CD68, α-smooth muscle actin (α-SMA), oxLDL and lectin-like oxLDL receptor-1 (LOX-1). Results We show that free cholesterol was colocalized with oxLDL in the wall of portal vein, and which was associated with lumen narrowing, plaque formation, endothelium deformation, and portal venous inflammation. The inflammation was evidenced by the colocalization of Kupffer cells and IL-1β and the expression of LOX-1. Notably, ruptured plaque was closely associated with portal venous inflammation. Moreover, free cholesterol and oxLDL accumulation in periportal and sinusoidal fibrosis, which was associated with regional stellate cell activation and chicken-wire fibrosis. Conclusion These findings reveal a direct association between cholesterol accumulation, portal venous inflammation and fibrosis in NAFLD. Electronic supplementary material The online version of this article (10.1186/s12950-019-0211-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Cheng-Maw Ho
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.,2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan
| | - Shu-Li Ho
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.,2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan.,8Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan
| | - Yung-Ming Jeng
- 3Department of Pathology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yu-Sheng Lai
- 4Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, 1, Jen Ai Rd, Sec 1, Taipei, 100 Taiwan
| | - Ya-Hui Chen
- 2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan.,5Department of Pediatrics, National Taiwan University Children Hospital, Taipei, Taiwan
| | - Shao-Chun Lu
- 4Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, 1, Jen Ai Rd, Sec 1, Taipei, 100 Taiwan
| | - Hui-Ling Chen
- 2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan
| | - Po-Yuan Chang
- 6Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Rey-Heng Hu
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Po-Huang Lee
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.,7Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
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Inter-reader agreement of magnetic resonance imaging proton density fat fraction and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis. Abdom Radiol (NY) 2019; 44:482-492. [PMID: 30128694 DOI: 10.1007/s00261-018-1745-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To determine the inter-reader agreement of magnetic resonance imaging proton density fat fraction (PDFF) and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis (NASH). STUDY TYPE We performed a secondary analysis of a placebo-controlled randomized clinical trial of a bile acid sequestrant in 45 adults with NASH. A six-echo spoiled gradient-recalled-echo magnitude-based fat quantification technique was performed at 3 T. Three independent readers measured MRI-PDFF by placing one primary and two additional regions of interest (ROIs) in each segment at both time points. Cross-sectional agreement between the three readers was evaluated using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Additionally, we used Bland-Altman analyses to examine pairwise agreement between the three readers at baseline, end of treatment (EOT), and for longitudinal change. RESULTS Using all ROIs by all readers, mean PDFF at baseline, at EOT, and mean change in PDFF was 16.1%, 16.0%, and 0.07%, respectively. The 27-ROI PDFF measurements had 0.998 ICC and 1.8% CV at baseline, 0.998 ICC and 1.8% CV at EOT, and 0.997 ICC for longitudinal change. The 9-ROI PDFF measurements had corresponding values of 0.997 and 2.6%, 0.996 and 2.4%, and 0.994. Using 27 ROIs, the magnitude of the bias between readers for whole-liver PDFF measurement ranged from 0.03% to 0.06% points at baseline, 0.01% to 0.07% points at EOT, and 0.01% to 0.02% points for longitudinal change. CONCLUSION Inter-reader agreement for measuring whole-liver PDFF and its longitudinal change is high. 9-ROI measurements have only slightly lower agreement than 27-ROI measurements.
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Pieńkowska J, Brzeska B, Kaszubowski M, Kozak O, Jankowska A, Szurowska E. MRI assessment of ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with the presence of central obesity and metabolic syndrome. Diabetes Metab Syndr Obes 2019; 12:623-636. [PMID: 31118724 PMCID: PMC6506015 DOI: 10.2147/dmso.s194690] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 02/22/2019] [Indexed: 12/16/2022] Open
Abstract
Purpose: Obesity, defined as a body mass index (BMI) exceeding 30 kg/m2, is a serious health problem, which can be called an epidemic on a global scale and is one of the most important causes of preventable death. The aim of this study was to assess ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with metabolic syndrome (MetS). Patients and methods: The study included 267 consecutive patients who underwent a standard clinical assessment with BMI calculation. Ectopic fat accumulation in pancreas, liver, and skeletal muscle was evaluated by magnetic resonance imaging (MRI) using fat-water separated Dixon imaging. MetS was defined according to the criteria modified by the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Central obesity was defined using gender and ethnic-specific values for waist circumference. Results: There was a statistically significant correlation between the degree of steatosis of the assessed organs and BMI value as well as waist circumference ratio, that determined the degree of central obesity. It was found that the most rapid relative fat accumulation was in muscle, then in pancreas and then in liver. Higher steatosis of pancreas, liver, and muscle was demonstrated depending on the number of the satisfied MetS criteria. Conclusion: Knowing that pancreatic fatty disease is a risk factor for MetS, it seems that assessment and monitoring of ectopic fat accumulation may have important clinical implications and may be used in the prediction of metabolic risk and its early prevention.
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Affiliation(s)
- Joanna Pieńkowska
- II Department of Radiology, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland
- Correspondence: Joanna PieńkowskaII Department of Radiology, Faculty of Health Sciences, Medical University of Gdansk, Mariana Smoluchowskiego 17, Gdansk80-214, PolandTel +4 858 349 3680Fax +4 858 349 3690Email
| | - Beata Brzeska
- II Department of Radiology, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland
- Department of Biology and Pharmaceutical Botany, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland
- Department of Human Physiology, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland
| | - Mariusz Kaszubowski
- Institute of Statistics, Department of Economic Sciences, Faculty of Management and Economics, Gdansk University of Technology, Gdansk, Poland
| | - Oliwia Kozak
- I Department of Radiology, Faculty of Medicine, Medical University of Gdansk, Gdansk, Poland
| | - Anna Jankowska
- Department of Radiology, University Clinical Centre in Gdansk, Gdansk, Poland
| | - Edyta Szurowska
- II Department of Radiology, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland
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Carino A, Marchianò S, Biagioli M, Bucci M, Vellecco V, Brancaleone V, Fiorucci C, Zampella A, Monti MC, Distrutti E, Fiorucci S. Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis. FASEB J 2018; 33:2809-2822. [PMID: 30303744 DOI: 10.1096/fj.201801373rr] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) is associated with an increased risk of developing cardiovascular complications and mortality, suggesting that treatment of NASH might benefit from combined approaches that target the liver and the cardiovascular components of NASH. Using genetic and pharmacologic approaches, we show that G protein-coupled bile acid-activated receptor 1 (GPBAR1) agonism reverses liver and vascular damage in mouse models of NASH. NASH is associated with accelerated vascular inflammation representing an independent risk factor for development of cardiovascular diseases and cardiovascular-related mortality. GPBAR1, also known as TGR5, is a G protein-coupled receptor for secondary bile acids that reduces inflammation and promotes energy expenditure. Using genetic and pharmacologic approaches, we investigated whether GPBAR1 agonism by 6β-ethyl-3α,7β-dihydroxy-5β-cholan-24-ol (BAR501) reverses liver and vascular damage induced by exposure to a diet enriched in fat and fructose (HFD-F). Treating HFD-F mice with BAR501 reversed liver injury and promoted the browning of white adipose tissue in a Gpbar1-dependent manner. Feeding HFD-F resulted in vascular damage, as shown by the increased aorta intima-media thickness and increased expression of inflammatory genes (IL-6,TNF-α, iNOS, and F4/80) and adhesion molecules (VCAM, intercellular adhesion molecule-1, and endothelial selectin) in the aorta, while reducing the expression of genes involved in NO and hydrogen sulfide generation, severely altering vasomotor activities of aortic rings in an ex vivo assay. BAR501 reversed this pattern in a Gpbar1-dependent manner, highlighting a potential role for GPBAR1 agonism in treating the liver and vascular component of NASH.-Carino, A., Marchianò, S., Biagioli, M., Bucci, M., Vellecco, V., Brancaleone, V., Fiorucci, C., Zampella, A., Monti, M. C., Distrutti, E., Fiorucci, S. Agonism for the bile acid receptor GPBAR1 reverses liver and vascular damage in a mouse model of steatohepatitis.
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Affiliation(s)
- Adriana Carino
- Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy
| | - Silvia Marchianò
- Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy
| | - Michele Biagioli
- Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy
| | | | | | | | - Chiara Fiorucci
- Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy
| | - Angela Zampella
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Maria Chiara Monti
- Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy; and
| | | | - Stefano Fiorucci
- Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy
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Bray TJP, Chouhan MD, Punwani S, Bainbridge A, Hall-Craggs MA. Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology. Br J Radiol 2018; 91:20170344. [PMID: 28936896 PMCID: PMC6223159 DOI: 10.1259/bjr.20170344] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/18/2017] [Accepted: 09/06/2017] [Indexed: 02/06/2023] Open
Abstract
Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (e.g. in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. MRI is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has, therefore, emerged as an objective, image-based biomarker of disease. Methods for FF quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method-and correct interpretation-can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians.
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Affiliation(s)
- Timothy JP Bray
- Centre for
Medical Imaging, University College London,University College London,
London, UK
| | - Manil D Chouhan
- Centre for
Medical Imaging, University College London,University College London,
London, UK
| | - Shonit Punwani
- Centre for
Medical Imaging, University College London,University College London,
London, UK
| | - Alan Bainbridge
- Department
of Medical Physics, University College London
Hospitals,University
College London Hospitals, London,
UK
| | - Margaret A Hall-Craggs
- Centre for
Medical Imaging, University College London,University College London,
London, UK
- Department
of Medical Physics, University College London
Hospitals,University
College London Hospitals, London,
UK
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Li Q, Dhyani M, Grajo JR, Sirlin C, Samir AE. Current status of imaging in nonalcoholic fatty liver disease. World J Hepatol 2018; 10:530-542. [PMID: 30190781 PMCID: PMC6120999 DOI: 10.4254/wjh.v10.i8.530] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/25/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic liver injury and progressive fibrosis in a significant minority. Effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard; however, non-invasive imaging methods are rapidly evolving and may replace biopsy in some circumstances. These methods include well-established techniques, such as conventional ultrasonography, computed tomography, and magnetic resonance imaging and newer imaging technologies, such as ultrasound elastography, quantitative ultrasound techniques, magnetic resonance elastography, and magnetic resonance-based fat quantitation techniques. The aim of this article is to review the current status of imaging methods for NAFLD risk stratification and management, including their diagnostic accuracy, limitations, and practical applicability.
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Affiliation(s)
- Qian Li
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Manish Dhyani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
- Department of Radiology, Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA 01805, United States
| | - Joseph R Grajo
- Department of Radiology, Division of Abdominal Imaging, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Claude Sirlin
- Altman Clinical Translational Research Institute, University of California, San Diego, CA 92103, United States
| | - Anthony E Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
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Ultrasound Grade of Liver Steatosis Is Independently Associated with the Risk of Metabolic Syndrome. Can J Gastroenterol Hepatol 2018; 2018:8490242. [PMID: 30211140 PMCID: PMC6126110 DOI: 10.1155/2018/8490242] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022] Open
Abstract
The aim of the study was to explore (a) prevalence and grade of nonalcoholic fatty liver (NAFL) among outpatients referred for abdominal ultrasound (US) examination and (b) relationship between the presence and severity of liver steatosis and metabolic syndrome (MS). This was a retrospective analysis of patients without history of liver disease examined by abdominal US in the University hospital setting. US was used to detect and semiquantitatively grade (0-3) liver steatosis. Data on patients' age, gender, body mass index (BMI), impaired glucose metabolism (IGM), atherogenic dyslipidaemia (AD), raised blood pressure (RBP), transaminases, and platelet counts were obtained from medical records. MS was defined as having at least 3 of the following components: obesity, IGM, AD, and RBP. Of the 631 patients (median age 60 years, median BMI 27.4 kg/m2, and 57.4% females) 71.5% were overweight and 48.5% had NAFL. In the subgroup of 159 patients with available data on the components of MS, patients with higher US grade of steatosis had significantly higher BMI and increased prevalence of obesity, IGM, AD, RBP, and accordingly more frequently had MS, whereas they did not differ in terms of age and gender. NAFL was independently associated with the risk of having MS in a multivariate model adjusted for age, gender, BMI, and IGM. The grade of liver steatosis did not correlate with the presence of liver fibrosis. We demonstrated worrisome prevalence of obesity and NAFL in the outpatient population from our geographic region. NAFL is independently associated with the risk of having MS implying worse prognosis.
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Spahis S, Alvarez F, Ahmed N, Dubois J, Jalbout R, Paganelli M, Grzywacz K, Delvin E, Peretti N, Levy E. Non-alcoholic fatty liver disease severity and metabolic complications in obese children: impact of omega-3 fatty acids. J Nutr Biochem 2018; 58:28-36. [PMID: 29864682 DOI: 10.1016/j.jnutbio.2018.03.025] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 03/24/2018] [Accepted: 03/26/2018] [Indexed: 02/06/2023]
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49
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Quantification of Liver Fat Content With Unenhanced MDCT: Phantom and Clinical Correlation With MRI Proton Density Fat Fraction. AJR Am J Roentgenol 2018; 211:W151-W157. [PMID: 30016142 DOI: 10.2214/ajr.17.19391] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The purpose of this study was to evaluate the relation between unenhanced CT liver attenuation values and MRI-derived proton density fat fraction (PDFF) for estimation of liver fat content at CT. MATERIALS AND METHODS A CT-MRI phantom was constructed and imaged containing 12 vials with lipid fractions ranging from 0% to 100%. For the retrospective clinical arm, 221 patients (120 men, 101 women; mean age, 54 years) underwent both unenhanced CT and chemical shift-encoded MRI of the liver between 2007 and 2017. Among these patients, 92 had more than one 120-kV CT scan for comparison. CT attenuation and MRI PDFF were derived with coregistered ROI measurements in the right hepatic lobe. The 120-kV subgroup of CT examinations performed within 1 month of MRI PDFF examinations (n = 72) served as the primary cohort for linear correlation. The effects of different tube voltage settings, time intervals between CT and MRI, and iron overload were assessed. Linear least squares regression analysis was performed. RESULTS Phantom results showed excellent linear fit between CT attenuation and MRI PDFF (r2 = 0.986). In patients, 120-kV CT performed within 1 month of MRI PDFF exhibited strong linear correlation (r2 = 0.828) that closely matched the phantom data, yielding the following clinical CT-MRI conversion formula: MRI PDFF (%) = -0.58 × CT attenuation (HU) + 38.2. Correlation worsened for CT-to-MRI intervals longer than 1 month (r2 = 0.565), and this specific relationship did not apply as well to non-120-kV settings (r2 = 0.554). For patients with multiple scans, correlation progressively worsened over time. CT-based liver fat content was underestimated in several patients with iron overload. CONCLUSION The linear correlation between unenhanced CT attenuation and MRI PDFF allows quantification of liver fat content by means of unenhanced CT in clinical practice. As expected, correlation worsened with increasing CT-MRI time interval, variable tube voltage settings, and iron overload.
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Kim SR, Lerman LO. Diagnostic imaging in the management of patients with metabolic syndrome. Transl Res 2018; 194:1-18. [PMID: 29175480 PMCID: PMC5839955 DOI: 10.1016/j.trsl.2017.10.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 10/18/2017] [Accepted: 10/26/2017] [Indexed: 02/07/2023]
Abstract
Metabolic syndrome (MetS) is the constellation of metabolic risk factors that might foster development of type 2 diabetes and cardiovascular disease. Abdominal obesity and insulin resistance play a prominent role among all metabolic traits of MetS. Because intervention including weight loss can reduce these morbidity and mortality in MetS, early detection of the severity and complications of MetS could be useful. Recent advances in imaging modalities have provided significant insight into the development and progression of abdominal obesity and insulin resistance, as well as target organ injuries. The purpose of this review is to summarize advances in diagnostic imaging modalities in MetS that can be applied for evaluating each components and target organs. This may help in early detection, monitoring target organ injury, and in turn developing novel therapeutic target to alleviate and avert them.
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Affiliation(s)
- Seo Rin Kim
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn
| | - Lilach O Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn.
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