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1
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Wu Z, Zhang M, Yan MK, Li C, Pan G, Xuan L. Synthesis and biological evaluation of amino-conjugated bile acid derivatives against non-alcoholic steatohepatitis. Bioorg Med Chem Lett 2025; 122:130210. [PMID: 40139332 DOI: 10.1016/j.bmcl.2025.130210] [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: 12/19/2024] [Revised: 02/24/2025] [Accepted: 03/23/2025] [Indexed: 03/29/2025]
Abstract
Non-alcoholic steatohepatitis (NASH) is emerging as a rapidly growing health concern. Bile acids (BAs) function as endocrine signaling molecules and exhibit therapeutic potential for NASH. To develop safer and more effective BA derivatives for NASH treatment, 25 amino acid-conjugated bile acid derivatives were designed and synthesized based on the pharmacological properties of the leading compound A17. The anti-lipid accumulation, anti-inflammatory and anti-fibrosis activities of these compounds were evaluated, and their structure-activity relationships were elucidated. Notably, compound C04 exhibited superior in vitro activity compared to obeticholic acid and demonstrated enhanced efficacy in improving both NASH and fibrosis in preclinical murine models via oral administration. These findings suggest that C04 is a promising candidate for NASH treatment and warrants further investigation.
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Affiliation(s)
- Zhitao Wu
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China; State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China
| | - Mingge Zhang
- State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China
| | - Meng Kun Yan
- State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China
| | - Chenyue Li
- State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; School of Pharmacy, Fudan University, Shanghai 201203, PR China
| | - Guoyu Pan
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China; State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
| | - Lijiang Xuan
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China; State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences,501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
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Liu B, Yin H, Li Y, Mao G, Yang S, Zhang K. Recent Advances in Small Molecular Fluorescence Probes for Fatty Liver Diseases. CHEMOSENSORS 2023; 11:241. [DOI: 10.3390/chemosensors11040241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Fatty liver diseases are a spectrum of liver disorders consisting of the benign fatty liver, which could eventually lead to cirrhosis or even hepatocellular cancer (HCC) without timely treatment. Therefore, early diagnosis is crucial for fatty liver diseases. Liver biopsy is regarded as the gold standard in the diagnosis of fatty liver diseases. However, it is not recommended for routine use due to its invasiveness and complicated operation. Thus, it is urgent to diagnose fatty liver diseases with non-invasive and precise methods. In this regard, fluorescence imaging technology has attracted intensive attention and become a robust non-invasive method for fatty liver visualization, and a series of fluorescent probes are being intensively designed to track the biomarkers in fatty liver. In this brief review, the small molecular fluorescent probes employed in fatty liver are summarized, mainly focusing on the last four years. Moreover, current opportunities and challenges in the development of fluorescent probes for fatty liver will be highlighted.
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Affiliation(s)
- Bo Liu
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Honghui Yin
- Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China
| | - Yaxiong Li
- Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China
| | - Guojiang Mao
- Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China
| | - Sheng Yang
- Laboratory of Chemical Biology & Traditional Chinese Medicine Research, Ministry of Education, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China
| | - Kai Zhang
- School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China
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Silva AC, Nogueira P, Machado MV. Hepatic steatosis after liver transplantation: a systematic review and meta-analysis. Liver Transpl 2023; 29:431-448. [PMID: 36735478 DOI: 10.1097/lvt.0000000000000060] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/16/2022] [Indexed: 02/04/2023]
Abstract
NAFLD can occur after liver transplantation (LT), as recurrence or de novo hepatic steatosis (HS). We aimed to evaluate the literature on prevalence, risk factors, and prognosis of post-LT HS. Systematic review with meta-analysis through a search on: PUBMED, Scopus, and Web-of-Science, from inception until the September 30, 2021. Forty studies were included, representing 6979 patients. The post-LT HS prevalence was 39.76% (95% CI, 34.06-45.46), with a rising kinetics (11.06% increase per decade, p =0.04), and a geographical distribution (15.10% more prevalent in American continent compared with Europe and Asia). Recurrent HS was up to 5-fold more likely than de novo HS [OR: 5.38 (2.69-10.76)]. Metabolic disturbances were stronger risk factors in the post-LT recipient [obesity: OR: 4.62 (3.07-6.96); metabolic syndrome: OR: 3.26 (2.03-5.25)] as compared with pre-LT recipients, with the exception of diabetes mellitus, which doubled the risk at any set [pre-LT diabetes mellitus: OR: 2.06 (1.58-2.68); post-LT diabetes mellitus: OR: 2.12 (1.73-2.59)]. Donor factors were not the relevant risk factors for post-LT HS and the only immunosuppressive drug associated with increased risk was sirolimus [OR: 1.68 (1.07-2.64)]. The prevalence of post-LT steatohepatitis was 28.82% (19.62-38.03) and the strongest risk factor was pre-LT NAFLD. Limited outcomes data suggest that post-LT HS did not increase the risk for liver cirrhosis or mortality in these studies. Two out of 5 patients submitted to LT will develop post-LT HS, being recurrent HS more common than de novo HS. Diabetes mellitus and post-LT metabolic syndrome are the strongest risk factors for HS and baseline NAFLD for steatohepatitis. All transplanted patients should be enrolled in lifestyle interventions to prevent post-LT metabolic syndrome, and sirolimus should be avoided in high-risk patients.
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Affiliation(s)
- Ana C Silva
- Gastroenterology Department, Medicine School, Lisbon University, Lisbon, Portugal
| | - Paulo Nogueira
- Biostatistic Department, Medicine School, Lisbon University, Lisbon, Portugal
| | - Mariana V Machado
- Gastroenterology Department, Medicine School, Lisbon University, Lisbon, Portugal
- Gastroenterology Department, Vila Franca de Xira Hospital, Lisbon, Portugal
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Iacob S, Beckebaum S, Iacob R, Gheorghe C, Cicinnati V, Popescu I, Gheorghe L. Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation. Front Nutr 2022; 8:787430. [PMID: 35096933 PMCID: PMC8795078 DOI: 10.3389/fnut.2021.787430] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/22/2021] [Indexed: 12/11/2022] Open
Abstract
Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.
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Affiliation(s)
- Speranta Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
- *Correspondence: Speranta Iacob
| | | | - Razvan Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Cristian Gheorghe
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | | | - Irinel Popescu
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Liana Gheorghe
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
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Satapathy SK, Tran QT, Kovalic AJ, Bontha SV, Jiang Y, Kedia S, Karri S, Mupparaju V, Podila PSB, Verma R, Maluf D, Mas V, Nair S, Eason JD, Bridges D, Kleiner DE. Clinical and Genetic Risk Factors of Recurrent Nonalcoholic Fatty Liver Disease After Liver Transplantation. Clin Transl Gastroenterol 2021; 12:e00302. [PMID: 33555168 PMCID: PMC7864756 DOI: 10.14309/ctg.0000000000000302] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 12/18/2020] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) has been increasingly reported among recipients of liver transplantation (LT). We aimed to identify clinical and genetic risk factors responsible for the development of early recurrent NAFLD in nonalcoholic steatohepatitis transplant recipients. METHODS Forty-six total single nucleotide polymorphisms with known association with NAFLD were tested among both recipient and donor liver samples in 66 LT recipients with nonalcoholic steatohepatitis to characterize influences on NAFLD recurrence at ∼1 year post-LT (median interval from LT to biopsy: 377 days). RESULTS Recurrent NAFLD was identified in 43 (65.2%) patients, 20 (30.3%) with mild recurrence, and 23 (34.8%) with moderate to severe NAFLD. On adjusted analysis, change in the body mass index (BMI) (ΔBMI) was significantly associated with NAFLD recurrence, whereas post-LT diabetes mellitus was associated with increased severity of NAFLD recurrence. ADIPOR1 rs10920533 in the recipient was associated with increased risk of moderate to severe NAFLD recurrence, whereas the minor allele of SOD2 rs4880 in the recipient was associated with reduced risk. Similar reduced risk was noted in the presence of donor SOD2 rs4880 and HSD17B13 rs6834314 polymorphism. DISCUSSION Increased BMI post-LT is strongly associated with NAFLD recurrence, whereas post-LT diabetes mellitus was associated with increased severity of NAFLD recurrence. Both donor and recipient SOD2 rs4880 and donor HSD17B13 rs6834314 single nucleotide polymorphisms may be associated with reduced risk of early NAFLD recurrence, whereas presence of the minor allele form of ADIPOR1 rs10920533 in the recipient is associated with increased severity NAFLD recurrence.
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Affiliation(s)
- Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, New York, USA
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Quynh T. Tran
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, College of Medicine, Memphis, Tennessee, USA
| | - Alexander J. Kovalic
- Department of Internal Medicine, University of Tennessee Health Sciences Center, College of Medicine, Memphis, Tennessee, USA
| | - Sai Vineela Bontha
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Yu Jiang
- School of Public Health, University of Memphis, Memphis, Tennessee, USA
| | - Satish Kedia
- School of Public Health, University of Memphis, Memphis, Tennessee, USA
| | - Saradashri Karri
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Vamsee Mupparaju
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Pradeep S. B. Podila
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Rajanshu Verma
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Daniel Maluf
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
- University of Maryland School of Medicine, Baltimore, MD, USA
| | - Valeria Mas
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
| | - Satheesh Nair
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - James D. Eason
- James D. Eason Transplant Institute, Methodist University Hospital, Memphis, Tennessee
- Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Dave Bridges
- Department of Nutritional Sciences University of Michigan School of Public Health, Ann Arbor, Michigan, USA
| | - David E. Kleiner
- Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
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6
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Batisti J, Mehal WZ. Nonalcoholic Fatty Liver Disease in the Post Liver Transplant Patient. CURRENT TRANSPLANTATION REPORTS 2020. [DOI: 10.1007/s40472-020-00303-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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7
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Tanaka S, Fujita K, Makimoto K, Kanaoka M, Yakushiji K, Tanaka R, Harada N, Yoshizumi T. Relationships of accelerometer-determined physical activity with obesity, hypertension, diabetes, dyslipidemia, and health-related quality of life in patients after liver transplantation. Clin Transplant 2020; 34:e14117. [PMID: 33053602 DOI: 10.1111/ctr.14117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 09/22/2020] [Accepted: 09/30/2020] [Indexed: 11/28/2022]
Abstract
The contribution of physical activity (PA) to the prevention of metabolic abnormalities following liver transplantation (LT) has not been well documented. We aimed to assess PA in post-LT patients and to quantify its relationships with the development of postoperative metabolic abnormalities and health-related quality of life (HRQOL). We recruited 111 patients who had undergone LT ≥ 6 months previously. PA was measured by accelerometry, and HRQOL was evaluated using SF-8. PA was quantified as the number of steps per day, and the time spent performing moderate-to-vigorous PA and light PA per week. The prevalence of hypertension, diabetes, and dyslipidemia increased more than twofold following LT. The proportion of the participants with a sedentary lifestyle (<5000 steps/day) was 36%. Logistic regression analysis showed that postoperative hypertension and obesity were associated with preoperative body mass index and the number of steps taken (in 2000 steps/day increments). Preoperative diabetes was associated with obesity, and PA was associated with physical function-related HRQOL scores. Thus, increasing the number of steps taken per day has the potential to reduce hypertension and obesity, and PA could improve physical function-related HRQOL in patients following LT.
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Affiliation(s)
- Satomi Tanaka
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kimie Fujita
- Division of Health Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan
| | - Kiyoko Makimoto
- Department of Nursing, School of Nursing and Rehabilitation, Konan Women's University, Kobe, Japan
| | - Maki Kanaoka
- School of Nursing Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kanako Yakushiji
- Division of Health Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan
| | - Rumi Tanaka
- Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Steggerda JA, Mahendraraj K, Todo T, Noureddin M. Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre- and post-transplant: A multi-system challenge. World J Gastroenterol 2020; 26:4018-4035. [PMID: 32821068 PMCID: PMC7403794 DOI: 10.3748/wjg.v26.i28.4018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/07/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease worldwide, and the fastest growing indication for liver transplantation in the United States. NASH is now the leading etiology for liver transplantation in women, the second leading indication for men, and the most common cause amongst recipients aged 65 years and older. Patients with end-stage liver disease related to NASH represent a unique and challenging patient population due the high incidence of associated comorbid diseases, including obesity, type 2 diabetes (T2D), and hypertension. These challenges manifest in the pre-liver transplantation period with increased waitlist times and waitlist mortality. Furthermore, these patients carry considerable risk of morbidity and mortality both before after liver transplantation, with high rates of T2D, cardiovascular disease, chronic kidney disease, poor nutrition, and disease recurrence. Successful transplantation for these patients requires identification and management of their comorbidities in the face of liver failure. Multidisciplinary evaluations include a thorough pre-transplant workup with a complete cardiac evaluation, control of diabetes, nutritional support, and even, potentially, consultation with a bariatric surgeon. This article provides a comprehensive review of the conditions and challenges facing patients with NASH cirrhosis undergoing liver transplantation and provides recommendations for evaluation and management to optimize them before liver transplantation to produce successful outcomes.
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Affiliation(s)
- Justin A Steggerda
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Krishnaraj Mahendraraj
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Tsuyoshi Todo
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Mazen Noureddin
- Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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Wang J, He W, Tsai PJ, Chen PH, Ye M, Guo J, Su Z. Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease. Lipids Health Dis 2020; 19:72. [PMID: 32284046 PMCID: PMC7155254 DOI: 10.1186/s12944-020-01210-0] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 02/24/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common metabolic syndrome. Imbalances between liver lipid output and input are the direct causes of NAFLD, and hepatic steatosis is the pathological premise and basis for NAFLD progression. Mutual interaction between endoplasmic reticulum stress (ERS) and oxidative stress play important roles in NAFLD pathogenesis. Notably, mitochondria-associated membranes (MAMs) act as a structural bridges for functional clustering of molecules, particularly for Ca2+, lipids, and reactive oxygen species (ROS) exchange. Previous studies have examined the crucial roles of ERS and ROS in NAFLD and have shown that MAM structural and functional integrity determines normal ER- mitochondria communication. Upon disruption of MAM integrity, miscommunication directly or indirectly causes imbalances in Ca2+ homeostasis and increases ERS and oxidative stress. Here, we emphasize the involvement of MAMs in glucose and lipid metabolism, chronic inflammation and insulin resistance in NAFLD and summarize MAM-targeting drugs and compounds, most of which achieve their therapeutic or ameliorative effects on NAFLD by improving MAM integrity. Therefore, targeting MAMs may be a viable strategy for NAFLD treatment. This review provides new ideas and key points for basic NAFLD research and drug development centred on mitochondria and the endoplasmic reticulum.
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Affiliation(s)
- Jin Wang
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, 510006, China.,Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Wanping He
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, 510006, China.,Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Ping-Ju Tsai
- King-Prebiotics Biotechnology (TW) Co., LTD, 2F.-1, No. 250, Zhongshan Rd., Linkou Dist, New Taipei City, 24446, Taiwan
| | - Pei-Hsuan Chen
- King-Prebiotics Biotechnology (TW) Co., LTD, 2F.-1, No. 250, Zhongshan Rd., Linkou Dist, New Taipei City, 24446, Taiwan
| | - Manxiang Ye
- New Francisco (Yunfu City) Biotechnology Co, Ltd Swan-kan-chiau Ind. Dist., Kaofong Village, Yunfu City, Guangdong, China
| | - Jiao Guo
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
| | - Zhengquan Su
- Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
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Performance of B-mode ratio and 2D shear wave elastography for the detection and quantification of hepatic steatosis and fibrosis after liver transplantation. Eur J Gastroenterol Hepatol 2020; 32:222-230. [PMID: 31464783 DOI: 10.1097/meg.0000000000001500] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To evaluate the diagnostic performance of B-mode ratio and shear wave elastography (SWE) for the assessment of steatosis and liver fibrosis after liver transplantation. MATERIALS AND METHODS Patients hospitalized for a systematic check-up after liver transplantation underwent the same day hepatic ultrasound with B-mode ratio and SWE, followed by liver biopsy and biological examinations. Steatosis was measured using hepatorenal sonographic index of B-mode ratio and liver stiffness using SWE. Liver biopsy, used as gold standard, graded steatosis S0(<5%), S1(5-<33%), S2(33-<66%), or S3(≥66%) and liver fibrosis according to the Metavir score. The results were tested against two external validation cohorts. RESULTS Fifty-eight patients were included. Mean B-ratio value was significantly higher in patients with steatosis (0.95 ± 0.13 versus 1.39 ± 0.41, P < 0.001). A B-mode ratio cutoff values at least 0.985 was found optimal for steatosis' detection [area under the receiver operating characteristic curve (AUROC) 0.902 ± 0.05, sensitivity 95%, specificity 79%]. A B-mode ratio value below 0.9 ruled out steatosis and above 1.12 ruled in steatosis. Mean SWE value for patients without significant fibrosis (≤F1) was 15.90 ± 9.2 versus 19.27 ± 7.7 kPa for patients with fibrosis (P = 0.185). A 2D-SWE value below 7.85 kPa ruled out significant fibrosis and above 26.35 kPa ruled it in. CONCLUSION The B-mode ratio is an efficient and accurate tool for the noninvasive diagnostic of steatosis in postliver transplantation patients. Yet, because liver stiffness is higher in postliver transplantation patients, 2D-SWE is not reliable in the diagnosis of significant fibrosis after liver transplantation.
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11
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Samji NS, Verma R, Satapathy SK. Magnitude of Nonalcoholic Fatty Liver Disease: Western Perspective. J Clin Exp Hepatol 2019; 9:497-505. [PMID: 31516266 PMCID: PMC6728535 DOI: 10.1016/j.jceh.2019.05.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 05/07/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise worldwide, and it is estimated that this disquieting trend will continue for another 10-15 years before prevalence begins to decrease. NAFLD is the hepatic manifestation of metabolic syndrome. As obesity, diabetes, and other lifestyle-related diseases continue to rise, the spectrum of NAFLD, e.g., nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, liver-related morbidity, and mortality, will increase in parallel. Its widespread prevalence and associated economic burden have drawn significant attention, and a multitude of pharmaceutical companies are participating in active research trying to find a "cure". Unfortunately, as of now, no targeted treatment exists to treat this condition, and therefore, emphasis has been on its prevention. The current review focuses on the epidemiology, clinical characteristics, risk factors, and clinical outcomes of NAFLD in Western countries. It is important to understand the magnitude of NAFLD and its risk factors in Western countries where the prevalence of NAFLD has now reached epidemic proportions to identify the best strategy to prevent and possibly control this epidemic.
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Affiliation(s)
- Naga S. Samji
- Tenova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
| | - Rajanshu Verma
- Tenova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, 37311, USA
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN, 38139, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, 11030, USA
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