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Yang T, Yang B, Yin J, Hou C, Wang Q. Targeting Insulin Resistance and Liver Fibrosis: CKD Screening Priorities in MASLD. Biomedicines 2025; 13:842. [PMID: 40299399 PMCID: PMC12025161 DOI: 10.3390/biomedicines13040842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Revised: 03/20/2025] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Background and Aims: Chronic kidney disease (CKD) is a recognized extra-hepatic disease of nonalcoholic fatty liver disease (NAFLD). With the redefinition of NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), the importance of cardiovascular metabolic factors in MASLD has been highlighted. However, whether MASLD remains independently associated with the prevalence of CKD is yet to be determined. Method: We analyzed data from 6567 non-pregnant adults from the National Health and Nutrition Examination Survey 2017-2020. MASLD was identified using liver ultrasound transient elastography and five cardiovascular risk factors. Multivariate logistic regression, subgroup analysis, and restricted cubic splines were employed to explore the associations and interactions within the data. Results: The prevalence of CKD across MASLD subgroups with different combinations of cardiometabolic risk factors varied. Univariate regression analysis indicated a significant association between MASLD and CKD (OR: 1.68, p < 0.001). This association was not significant after adjusting for diabetes (OR: 0.94, p = 0.74) or insulin resistance (OR: 1.00, p = 0.98) and was not significant in the fully adjusted model (OR: 0.87, p = 0.64). Subgroup analysis confirmed insulin resistance as a modifier in the MASLD-CKD relationship (p for interaction = 0.02). Multivariate analysis revealed that liver stiffness measurements (LSMs) were independently associated with CKD. LSM values showed an S-shaped correlation with CKD, with risk increasing above the 8.612 kPa threshold. Conclusions: This study suggests that the direct relationship between MASLD and CKD diminished when accounting for insulin resistance. Nevertheless, liver fibrosis emerges as an independent CKD risk factor, emphasizing the critical need for targeted CKD screening among MASLD patients, particularly those with insulin resistance or advanced fibrosis.
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Affiliation(s)
- Tianyuan Yang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; (T.Y.); (B.Y.); (J.Y.)
| | - Bingqing Yang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; (T.Y.); (B.Y.); (J.Y.)
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Jingya Yin
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; (T.Y.); (B.Y.); (J.Y.)
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Chenxue Hou
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China;
| | - Qi Wang
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; (T.Y.); (B.Y.); (J.Y.)
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Wada N, Iwaki M, Kobayashi T, Nakajima A, Yoneda M. Reducing complications of metabolic dysfunction-associated steatotic liver disease. Expert Rev Gastroenterol Hepatol 2025; 19:577-588. [PMID: 40366767 DOI: 10.1080/17474124.2025.2502549] [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: 02/03/2025] [Accepted: 05/02/2025] [Indexed: 05/16/2025]
Abstract
INTRODUCTION Complications from metabolic dysfunction-associated steatotic liver disease (MASLD) include liver-related and extrahepatic complications, and the all-cause mortality rate is significantly higher in patients with MASLD than in those without MASLD. AREAS COVERED We review the complications of MASLD and their management based on the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines as well as medical papers. For the papers, we focused on studies referenced in the EASL and AASLD guidelines. Additionally, a search was conducted in PubMed to gather relevant literature. EXPERT OPINION Identifying and managing MASLD early, before it progresses to cirrhosis, is crucial to reducing mortality rates, and collaboration among healthcare professionals, including dietitians, nurses, and physical therapists, is vital for comprehensive management. There is active development of new drugs for MASLD, and we hope that new treatments will be developed soon.
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Affiliation(s)
- Naohiro Wada
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Michihiro Iwaki
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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3
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Bhattacharya CS, Pizzato PE, Heijer M, Sunnåker M, Holden J, Trebski M, Nelander K, Ali H, Genov DK, Aurell M, Collén A, Ericsson H. The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of mitiperstat. Br J Clin Pharmacol 2024; 90:3212-3220. [PMID: 39134325 PMCID: PMC11602950 DOI: 10.1111/bcp.16205] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/05/2024] [Accepted: 07/08/2024] [Indexed: 11/29/2024] Open
Abstract
AIMS Mitiperstat is a novel, highly potent myeloperoxidase inhibitor being evaluated in patients with cardio-metabolic disease (phase 2). These patients often have impaired renal function, which may affect mitiperstat pharmacokinetics. This study assessed mitiperstat pharmacokinetics, safety and tolerability in participants with severe renal impairment and normal renal function, to inform inclusion of participants with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 in phase 3. METHODS Participants with severe renal impairment (eGFR ≥15 and <30 mL/min/1.73 m2) who were not on dialysis (n = 10) and group-matched controls (eGFR ≥90 mL/min/1.73 m2; n = 10) received a single mitiperstat 2.5 mg oral tablet. Blood samples were collected at intervals for 2 weeks and urine samples for 24 h post-dose. RESULTS Total apparent mitiperstat clearance was 10.83 L/h in the severe renal impairment cohort and 25.62 L/h in the control cohort. The area under the plasma concentration-time curve was 2.37-fold higher (90% confidence interval [CI]: 1.79, 3.12) in the severe renal impairment cohort than in the control cohort, with longer elimination half-life and similar maximum concentration. Non-renal clearance was similar between the cohorts. CONCLUSIONS Mitiperstat apparent clearance was approximately twofold lower in individuals with severe renal impairment than in those with normal renal function. Lower clearance was driven by reduced renal clearance; non-renal clearance was similar. Mitiperstat was generally well tolerated by participants with severe renal impairment and normal renal function. These findings, together with efficacy and safety/tolerability data from phase 2b, will guide the dosing regimen for phase 3.
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Affiliation(s)
- Chandrali S. Bhattacharya
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety SciencesBioPharmaceuticals R&D, AstraZenecaGaithersburgMDUSA
| | - Patricia Ely Pizzato
- Early Clinical Development, Research and Early Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&DAstraZenecaGaithersburgMDUSA
| | - Maria Heijer
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&DAstraZenecaGothenburgSweden
| | - Mikael Sunnåker
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&DAstraZenecaGothenburgSweden
| | - Julie Holden
- Patient Safety, BioPharmaceuticals R&DAstraZenecaGaithersburgMDUSA
| | - Monika Trebski
- Patient Safety, BioPharmaceuticals R&DAstraZenecaGaithersburgMDUSA
| | - Karin Nelander
- Biometrics, Late Cardiovascular Renal and Metabolism, BioPharmaceuticals R&DAstraZenecaGothenburgSweden
| | - Hodan Ali
- Late‐Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&DAstraZenecaGaithersburgMDUSA
| | | | - Malin Aurell
- Early Clinical Development, Research and Early Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&DAstraZenecaGaithersburgMDUSA
| | - Anna Collén
- Projects, Research and Early Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&DAstraZenecaGothenburgSweden
| | - Hans Ericsson
- Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&DAstraZenecaGothenburgSweden
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Vogel AS, Roediger R, von Ahrens D, Fortune BE, Schwartz JM, Frager S, Chacko KR, Tow CY. The Impact of Metabolic Health and Obesity on Liver Transplant Candidates and Recipients. Life (Basel) 2024; 14:685. [PMID: 38929668 PMCID: PMC11204519 DOI: 10.3390/life14060685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 04/12/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Poor metabolic health and obesity have significant impacts on the outcomes of patients suffering from chronic liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease. Patients with such comorbidities who require liver transplant evaluation for advancing liver disease or liver failure require special consideration due to increased risk of cardiovascular disease, renal dysfunction, sarcopenic obesity, and cancer. Those who have had a history of prior bariatric surgery pose specific anatomical constraints and may also be at increased risk of alcohol use disorder. Pre-operative risk assessment as well as strict control of metabolic risk factors are essential to reduce intra-operative and post-liver transplant complications. As immunosuppressive therapy exacerbates metabolic dysfunction and risk for cancer, post-liver transplant care must focus on balancing the need to prevent rejection and the impact of progressive metabolic dysfunction in this unique, but growing, patient population.
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Affiliation(s)
| | | | | | | | | | | | | | - Clara Y. Tow
- Correspondence: ; Tel.: +1-888-795-4837; Fax: +1-602-563-8224
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Chen IC, Chou LJ, Huang SC, Chu TW, Lee SS. Machine learning-based comparison of factors influencing estimated glomerular filtration rate in Chinese women with or without non-alcoholic fatty liver. World J Clin Cases 2024; 12:2506-2521. [PMID: 38817230 PMCID: PMC11135451 DOI: 10.12998/wjcc.v12.i15.2506] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 02/13/2024] [Accepted: 04/09/2024] [Indexed: 05/14/2024] Open
Abstract
BACKGROUND The prevalence of non-alcoholic fatty liver (NAFLD) has increased recently. Subjects with NAFLD are known to have higher chance for renal function impairment. Many past studies used traditional multiple linear regression (MLR) to identify risk factors for decreased estimated glomerular filtration rate (eGFR). However, medical research is increasingly relying on emerging machine learning (Mach-L) methods. The present study enrolled healthy women to identify factors affecting eGFR in subjects with and without NAFLD (NAFLD+, NAFLD-) and to rank their importance. AIM To uses three different Mach-L methods to identify key impact factors for eGFR in healthy women with and without NAFLD. METHODS A total of 65535 healthy female study participants were enrolled from the Taiwan MJ cohort, accounting for 32 independent variables including demographic, biochemistry and lifestyle parameters (independent variables), while eGFR was used as the dependent variable. Aside from MLR, three Mach-L methods were applied, including stochastic gradient boosting, eXtreme gradient boosting and elastic net. Errors of estimation were used to define method accuracy, where smaller degree of error indicated better model performance. RESULTS Income, albumin, eGFR, High density lipoprotein-Cholesterol, phosphorus, forced expiratory volume in one second (FEV1), and sleep time were all lower in the NAFLD+ group, while other factors were all significantly higher except for smoking area. Mach-L had lower estimation errors, thus outperforming MLR. In Model 1, age, uric acid (UA), FEV1, plasma calcium level (Ca), plasma albumin level (Alb) and T-bilirubin were the most important factors in the NAFLD+ group, as opposed to age, UA, FEV1, Alb, lactic dehydrogenase (LDH) and Ca for the NAFLD- group. Given the importance percentage was much higher than the 2nd important factor, we built Model 2 by removing age. CONCLUSION The eGFR were lower in the NAFLD+ group compared to the NAFLD- group, with age being was the most important impact factor in both groups of healthy Chinese women, followed by LDH, UA, FEV1 and Alb. However, for the NAFLD- group, TSH and SBP were the 5th and 6th most important factors, as opposed to Ca and BF in the NAFLD+ group.
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Affiliation(s)
- I-Chien Chen
- Department of Nursing, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Lin-Ju Chou
- Department of Nursing, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Shih-Chen Huang
- Department of Nursing, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Ta-Wei Chu
- Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
- Chief Executive Officer's Office, MJ Health Research Foundation, Taipei 114, Taiwan
| | - Shang-Sen Lee
- Department of Urology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan
- School of Medicine, Tzu Chi University, Hualian 970, Taiwan
- Department of Urology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
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6
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Moreno J, Gluud LL, Galsgaard ED, Hvid H, Mazzoni G, Das V. Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics. PLoS One 2024; 19:e0302853. [PMID: 38768139 PMCID: PMC11104622 DOI: 10.1371/journal.pone.0302853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/10/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Chronic Kidney Disease (CKD) and Metabolic dysfunction-associated steatohepatitis (MASH) are metabolic fibroinflammatory diseases. Combining single-cell (scRNAseq) and spatial transcriptomics (ST) could give unprecedented molecular disease understanding at single-cell resolution. A more comprehensive analysis of the cell-specific ligand-receptor (L-R) interactions could provide pivotal information about signaling pathways in CKD and MASH. To achieve this, we created an integrative analysis framework in CKD and MASH from two available human cohorts. RESULTS The analytical framework identified L-R pairs involved in cellular crosstalk in CKD and MASH. Interactions between cell types identified using scRNAseq data were validated by checking the spatial co-presence using the ST data and the co-expression of the communicating targets. Multiple L-R protein pairs identified are known key players in CKD and MASH, while others are novel potential targets previously observed only in animal models. CONCLUSION Our study highlights the importance of integrating different modalities of transcriptomic data for a better understanding of the molecular mechanisms. The combination of single-cell resolution from scRNAseq data, combined with tissue slide investigations and visualization of cell-cell interactions obtained through ST, paves the way for the identification of future potential therapeutic targets and developing effective therapies.
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Affiliation(s)
- Jaime Moreno
- Digital Science and Innovation, Computational Biology – AI & Digital Research, Novo Nordisk A/S, Maløv, Denmark
| | - Lise Lotte Gluud
- Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Dept of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | | | - Henning Hvid
- Global Drug Discovery, Novo Nordisk A/S, Maløv, Denmark
| | - Gianluca Mazzoni
- Digital Science and Innovation, Computational Biology – AI & Digital Research, Novo Nordisk A/S, Maløv, Denmark
| | - Vivek Das
- Digital Science and Innovation, Computational Biology – AI & Digital Research, Novo Nordisk A/S, Maløv, Denmark
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Lee HH, Ro H, Jung JY, Chang JH, Chung W, Kim AJ. The Fatty Liver Index's Association with Incident Chronic Kidney Disease in Korean Middle-Aged Adults: A Community-Based Cohort Study. J Clin Med 2024; 13:1616. [PMID: 38541842 PMCID: PMC10971018 DOI: 10.3390/jcm13061616] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/08/2024] [Accepted: 03/09/2024] [Indexed: 01/03/2025] Open
Abstract
(1) Background: The relationship between nonalcoholic fatty liver disease (NAFLD) and incident chronic kidney disease (CKD) is unclear, and long-term follow-up data are limited. Therefore, this study aimed to evaluate whether NAFLD, as assessed by the fatty liver index (FLI), could predict the development of CKD in a community-based Korean cohort over 16 years. (2) Methods: Among the 10,030 total participants, 7778 patients without CKD were selected from the Korean Genome and Epidemiology Study (KoGES). The FLI grade ranged from 0 to 100 and was divided into three groups: low (FLI, <30), intermediate (FLI, 30-59), and high (FLI, ≥60). An estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or the development of proteinuria was considered to indicate incident CKD. (3) Results: During the 16-year follow-up period, 919 individuals (11.8%) developed CKD. The HRs of incident CKD in the intermediate FLI group (30-59) and high FLI group (≥60) increased compared with the reference low FLI group (<30) after adjusting for potentially confounding variables. NAFLD, as assessed by the FLI, was an independent risk factor for CKD. (4) Conclusions: Our findings suggest that the FLI, a simple surrogate biomarker of fatty liver disease, may be used to identify people at high risk of incident CKD in clinical practice.
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Affiliation(s)
- Hyun Hee Lee
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Han Ro
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Ji Yong Jung
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Jae Hyun Chang
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Wookyung Chung
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Ae Jin Kim
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon 21565, Republic of Korea
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Boncan DAT, Yu Y, Zhang M, Lian J, Vardhanabhuti V. Machine learning prediction of hepatic steatosis using body composition parameters: A UK Biobank Study. NPJ AGING 2024; 10:4. [PMID: 38195699 PMCID: PMC10776620 DOI: 10.1038/s41514-023-00127-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 10/16/2023] [Indexed: 01/11/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease worldwide, yet detection has remained largely based on surrogate serum biomarkers, elastography or biopsy. In this study, we used a total of 2959 participants from the UK biobank cohort and established the association of dual-energy X-ray absorptiometry (DXA)-derived body composition parameters and leveraged machine learning models to predict NAFLD. Hepatic steatosis reference was based on MRI-PDFF which has been extensively validated previously. We found several significant associations with traditional measurements such as abdominal obesity, as defined by waist-to-hip ratio (OR = 2.50 (male), 3.35 (female)), android-gynoid ratio (OR = 3.35 (male), 6.39 (female)) and waist circumference (OR = 1.79 (male), 3.80 (female)) with hepatic steatosis. Similarly, A Body Shape Index (Quantile 4 OR = 1.89 (male), 5.81 (female)), and for fat mass index, both overweight (OR = 6.93 (male), 2.83 (female)) and obese (OR = 14.12 (male), 5.32 (female)) categories were likewise significantly associated with hepatic steatosis. DXA parameters were shown to be highly associated such as visceral adipose tissue mass (OR = 8.37 (male), 19.03 (female)), trunk fat mass (OR = 8.64 (male), 25.69 (female)) and android fat mass (OR = 7.93 (male), 21.77 (female)) with NAFLD. We trained machine learning classifiers with logistic regression and two histogram-based gradient boosting ensembles for the prediction of hepatic steatosis using traditional body composition indices and DXA parameters which achieved reasonable performance (AUC = 0.83-0.87). Based on SHapley Additive exPlanations (SHAP) analysis, DXA parameters that had the largest contribution to the classifiers were the features predicted with significant association with NAFLD. Overall, this study underscores the potential utility of DXA as a practical and potentially opportunistic method for the screening of hepatic steatosis.
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Affiliation(s)
- Delbert Almerick T Boncan
- Snowhill Science Ltd, Units 801-803, Level 8, Core C, Hong Kong SAR, China
- School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Yan Yu
- Snowhill Science Ltd, Units 801-803, Level 8, Core C, Hong Kong SAR, China
| | - Miaoru Zhang
- Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Jie Lian
- Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Varut Vardhanabhuti
- Snowhill Science Ltd, Units 801-803, Level 8, Core C, Hong Kong SAR, China.
- Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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Kasem HES, Abdelatty EA, Yahia AMM, Abdalla EM. The association between non-alcoholic fatty liver disease and chronic kidney disease in Egyptian patients. EGYPTIAN LIVER JOURNAL 2023; 13:63. [DOI: 10.1186/s43066-023-00297-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 11/05/2023] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
NAFLD is a spectrum of disorders ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH), NASH related cirrhosis and hepatocellular carcinoma (HCC). There is sparse data on the prevalence CKD in Egyptian patients with NAFLD. The aim of this study is to estimate the prevalence of CKD in the subjects with NAFLD and to assess the risk factors of CKD among them.
Methods
A cross-sectional study was conducted on 430 patients from the Internal Medicine Department, Menoufia University Hospitals, including 215 patients with NAFLD, and 215 patients without NAFLD. NAFLD was diagnosed by abdominal ultrasonography. The liver fibrosis was assessed by NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or abnormal albuminuria (urinary albumin-to-creatinine ratio ⩾ 30 mg/gm). The logistic regression analysis was performed to examine the association between NAFLD and risk of CKD.
Results
The prevalence of CKD was higher in individuals with NAFLD than in those without NAFLD (38.1% vs 7.4%, p < 0.001). Logistic regression analysis demonstrated that both NAFLD and CKD were risk factors of each other. The presence of hypertension, high levels of BMI and waist circumference were the other independent risk factors of NAFLD. While the presence of DM, and the high level of BMI were the other significant risk factors of CKD in the NAFLD group.
Conclusion
The presence and severity of NAFLD are associated with an increased risk of CKD.
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Yoneda M, Kobayashi T, Iwaki M, Nogami A, Saito S, Nakajima A. Nonalcoholic Fatty Liver Disease as a Systemic Disease and the Need for Multidisciplinary Care. Gut Liver 2023; 17:843-852. [PMID: 37560797 PMCID: PMC10651384 DOI: 10.5009/gnl220545] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/14/2023] [Accepted: 03/28/2023] [Indexed: 08/11/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease, and there has been a rapid increase in cases worldwide. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma and is also associated with an increased risk of cardiovascular disease or exacerbation of other organ diseases, thus posing a significant health problem from both a medical and a socioeconomic perspective. NAFLD is a systemic disease and requires the involvement of numerous medical professionals. Multidisciplinary collaboration, in which different professionals within different specialties come together and work together toward a common goal, supports better patient care by integrating perspectives of multiple experts and facilitating the exchange of opinions. Due to the large number of potential patients, gastroenterologists and hepatologists cannot manage the patients alone, and collaboration between specialists in various fields, including family doctors, dentists, nutritionists, and pharmacists is required for treatment of NAFLD. This review will discuss NAFLD from the perspective of various specialties and introduce multidisciplinary collaboration.
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Affiliation(s)
- Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Michihiro Iwaki
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Asako Nogami
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
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Hashim A, Maraey A, Elzanaty A, Zordok M, Elsharnoby H, Khalil M, Al Wahadneh O, Siragy H. Nonalcoholic Fatty Liver Disease Predicts Acute Kidney Injury Readmission in Heart Failure Hospitalizations: A Nationwide Analysis. Curr Probl Cardiol 2023; 48:101816. [PMID: 37211306 DOI: 10.1016/j.cpcardiol.2023.101816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 05/13/2023] [Indexed: 05/23/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been associated with the progression of chronic kidney disease. However, limited data is available on its impact on acute kidney injury (AKI) in heart failure(HF) patients. All primary adult HF admissions from the national readmission database of 2016-2019 were identified. Admissions from July to December of each year were excluded to allow 6 months of follow-up. Patients were stratified according to the presence of NAFLD. Complex multivariate cox regression was used to adjust for confounders and calculate the adjusted hazard ratio. A total of 420,893 weighted patients admitted with HF were included in our cohort, of whom 780 had a secondary diagnosis of NAFLD. Patients with NAFLD were younger, more likely to be female, and had higher rates of obesity and diabetes mellitus. Both groups had similar rates of chronic kidney disease irrespective of the stage. NAFLD was associated with an increased risk of 6-month readmission with AKI (26.8% vs 16.6%, adjusted hazard ratio:1.44, 95% CI [1.14-1.82], P = 0.003). The mean time to AKI readmission was 150 ± 44 days. NAFLD was associated with a shorter mean time to readmission (145 ± 45 vs 155 ± 42 days, β = -10 days, P = 0.044). Our study from a national database suggests that NAFLD is an independent predictor of 6-months readmission with AKI in patients admitted with HF. Further research is warranted to validate these findings.
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Affiliation(s)
- Ahmed Hashim
- Ain Shams University, Faculty of Medicine, Cairo, Egypt
| | - Ahmed Maraey
- Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL.
| | - Ahmed Elzanaty
- Department of Cardiovascular Medicine, University of Toledo, Toledo, OH
| | - Magdi Zordok
- Department of Internal Medicine, Catholic Medical Center, Manchester, NH
| | - Hadeer Elsharnoby
- Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL
| | - Mahmoud Khalil
- Department of Internal Medicine, Lincoln Medical Center, Bronx, NY
| | - Omar Al Wahadneh
- Department of Internal Medicine, Carle Foundation Hospital, Urbana, IL
| | - Helmy Siragy
- Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA
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12
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Calleri A, Alessandria C. Renal damage in Hepatorenal Syndrome: A still unsolved issue. Clin Res Hepatol Gastroenterol 2023; 47:102178. [PMID: 37453679 DOI: 10.1016/j.clinre.2023.102178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 07/02/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023]
Abstract
Acute kidney injury (AKI) is a common complication of cirrhosis, burdened by high morbidity and mortality rates and progression to chronic kidney disease. Hepatorenal syndrome (HRS) is a peculiar type of functional AKI observed in cirrhotic patients with ascites. HRS diagnosis is still clinical, once pre-renal azotemia and intrinsic kidney damage have been excluded by applying well-established and internationally adopted criteria. HRS is considered reversible because of the absence of intrinsic renal damage. However, HRS reversibility has been questioned, due to the lack of response to treatment with vasoconstrictors plus albumin in a relevant percentage of patients and to the persistence of renal dysfunction in HRS patients who underwent liver transplantation (LT). Indeed, LT is the only ultimate treatment, as it solves both liver failure and portal hypertension. Thus, the presence of renal damage in HRS can be hypothesized. In this scenario, neutrophil gelatinase-associated lipocalin (NGAL), one of the most promising biomarkers, may help in characterizing the type of renal injury, distinguishing between HRS and acute tubular necrosis. This review gathers the available evidence in favor and against the presence of structural lesions in HRS in terms of either renal histology and urinary biomarkers with a particular focus on NGAL. The ability to properly characterize which component of renal dysfunction prevails - functional rather than structural - entails a relevant clinical impact for the treatment of these patients, both in terms of medical therapy and liver vs. combined liver-kidney transplantation.
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Affiliation(s)
- Alberto Calleri
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Italy.
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13
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Carvalho KSD, Daltro CHDC, Almeida VA, Santos RRD, Cotrim HP. Chronic kidney disease and the severity of non-alcoholic fatty liver disease: a systematic review. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2023; 69:e20221348. [PMID: 37466587 PMCID: PMC10352016 DOI: 10.1590/1806-9282.20221348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 04/25/2023] [Indexed: 07/20/2023]
Affiliation(s)
| | - Carla Hilário da Cunha Daltro
- Universidade Federal da Bahia, School of Medicine, Postgraduate Program in Medicine and Health - Salvador (BA), Brazil
| | | | - Raquel Rocha Dos Santos
- Universidade Federal da Bahia, School of Medicine, Postgraduate Program in Medicine and Health - Salvador (BA), Brazil
| | - Helma Pinchemel Cotrim
- Universidade Federal da Bahia, School of Medicine, Postgraduate Program in Medicine and Health - Salvador (BA), Brazil
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14
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Nysather J, Kaya E, Manka P, Gudsoorkar P, Syn WK. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease Cross Talk. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:315-335. [PMID: 37657879 DOI: 10.1053/j.akdh.2023.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/14/2022] [Accepted: 04/04/2023] [Indexed: 09/03/2023]
Abstract
Nonalcoholic fatty liver disease is a multisystem condition with effects beyond the liver. The identification of chronic kidney disease as an independent mediator of nonalcoholic fatty liver disease or associated entity with shared cardiometabolic risk factors remains controversial and continues to draw scientific interest. With increasing prevalence of nonalcoholic fatty liver disease and lack of Food and Drug Administration approved therapies, these shared cardiometabolic risk factors have drawn significant attention. In this article, we review shared pathophysiological mechanisms between nonalcoholic fatty liver disease and chronic kidney disease along with current treatment strategies that might be useful for both disease processes.
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Affiliation(s)
- Jacob Nysather
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Eda Kaya
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Prakash Gudsoorkar
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Euskal Herriko Unibertsitatea/Universidad del País Vasco, Leioa, Spain.
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15
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Verma N, Singal AK. Editorial: The US burden of HRS-AKI-Putting numbers to the problem: Authors' reply. Aliment Pharmacol Ther 2023; 58:122-123. [PMID: 37307544 DOI: 10.1111/apt.17562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Affiliation(s)
- Nipun Verma
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Ashwani K Singal
- Department of Medicine, University of South Dakota Sanford School of Medicine, Vermillion, South Dakota, USA
- Avera Transplant Institute and Division of Hepatology, Sioux Falls, South Dakota, USA
- VA Medical Center, Sioux Falls, South Dakota, USA
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16
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Johira Y, Nakahara T, Kinami T, Yamasaki S, Kosaka M, Shirane Y, Miura R, Murakami S, Yano S, Amioka K, Naruto K, Ando Y, Kosaka Y, Kodama K, Uchikawa S, Fujino H, Ono A, Murakami E, Okamoto W, Yamauchi M, Kawaoka T, Hayes CN, Tsuge M, Imamura M, Aikata H, Oka S. Impact and usefulness of the transition to the new MAFLD classification for non-B, non-C HCC: a retrospective cohort study. BMC Gastroenterol 2023; 23:222. [PMID: 37380950 DOI: 10.1186/s12876-023-02851-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 06/09/2023] [Indexed: 06/30/2023] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new classification system for fatty liver disease. In this study, we investigated the clinical characteristics of patients with MAFLD-hepatocellular carcinoma (HCC) in comparison with those with nonalcoholic fatty liver disease (NAFLD) and considered the validity and challenges of the new criteria. METHODS This study included 237 untreated non-B, non-C HCC patients with hepatic steatosis. We examined the profile and laboratory findings of patients with MAFLD-HCC and NAFLD-HCC. We also classified MAFLD-HCC patients according to the factors on which the diagnosis was based and compared their clinical characteristics. RESULTS A total of 222 (94%) and 101 (43%) patients were diagnosed with MAFLD and NAFLD, respectively. MAFLD-HCC patients were more likely to be male than NAFLD-HCC, but there were no significant differences in metabolic indices, noninvasive liver fibrosis score or HCC status. In a study of MAFLD-HCC patients by diagnostic factor, those with overweight only were younger and had advanced liver fibrosis histologically, and when limited to patients younger than 70 years, the majority were overweight. Redefinition of overweight as BMI ≥ 25 reduced the number of MAFLD-HCC patients by only 5, from 222 to 217. CONCLUSIONS MAFLD accounted for the majority of non-B, non-C HCC cases with hepatic steatosis. Examination of additional cases and revision of the detailed criteria is needed so that it can be used to efficiently select patients with fatty liver who are at high risk of developing HCC.
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Affiliation(s)
- Yusuke Johira
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
| | - Takahiro Kinami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shintaro Yamasaki
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masanari Kosaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Shirane
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryoichi Miura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Serami Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shigeki Yano
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kei Amioka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kensuke Naruto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuwa Ando
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yumi Kosaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kenichiro Kodama
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Wataru Okamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - C Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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17
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Wang Z, Huang Y, Zhu M, Cao J, Xiong Z. TLR2 and CASP7 as the biomarkers associated with non-alcoholic fatty liver disease and chronic kidney disease. Biochem Biophys Res Commun 2023; 667:50-57. [PMID: 37209562 DOI: 10.1016/j.bbrc.2023.05.038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/04/2023] [Accepted: 05/13/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are both highly prevalent worldwide. Studies have confirmed the association between them, but the underlying pathophysiological mechanisms are not clear yet. This study aims to identify the genetic and molecular mechanisms influencing both diseases through a bioinformatics approach. RESULTS Fifty-four overlapping differentially expressed genes associated with NAFLD and CKD were obtained by analysis of microarray datasets GSE63067 and GSE66494 downloaded from Gene Expression Omnibus. Next, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Nine hub genes were screened using protein-protein interaction network and Cytoscape software, including TLR2, ICAM1, RELB, BIRC3, HIF1A, RIPK2, CASP7, IFNGR1 and MAP2K4. The receiver operating characteristic curve results showed that all hub genes have good diagnostic values for patients with NAFLD and CKD. The mRNA expression of nine hub genes was detected in NAFLD and CKD animal models, and it was found that the expression of TLR2 and CASP7 was significantly increased in both disease models. CONCLUSIONS TLR2 and CASP7 can be used as biomarkers for both diseases. Our study provided new insights for identifying potential biomarkers and valuable therapeutic leads in NAFLD and CKD.
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Affiliation(s)
- Ziwen Wang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yumei Huang
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Mengpei Zhu
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Jiali Cao
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Zhifan Xiong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Copur S, Yavuz F, Kanbay M. Thyroid hormone Beta receptor agonists for treatment of kidney disease: A promising agent? Eur J Clin Invest 2023; 53:e13939. [PMID: 36537819 DOI: 10.1111/eci.13939] [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: 11/13/2022] [Revised: 12/14/2022] [Accepted: 12/15/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND Chronic kidney disease is a common disorder affecting a significant portion of the adult population with high mortality and morbidity. Obesity and hyperlipidemia are prevalent in chronic kidney disease, and they may trigger fat accumulation in renal parenchyma and eventually fatty kidney. Chronic kidney disease and fatty kidney are also strongly associated with nonalcoholic fatty liver disease. Because they both lead to detrimental effects on organ function, they both need to be treated effectively to improve the outcome. AIM In this narrative review, we have hypothesized that thyroid hormone beta receptor agonists, a novel drug group, may potentially be beneficial in the management of chronic kidney disease due to its promising outcomes among patients with nonalcoholic fatty liver disease, a condition sharing multiple common underlying pathophysiological mechanisms. RESULTS AND CONCLUSION Thyroid hormone beta receptors are abundantly expressed in liver and kidney tissues, while both nonalcoholic fatty liver disease and chronic kidney disease share various similar pathophysiological mechanisms and triggers. Therefore, thyroid hormone beta receptor agonists may become a promising tool in the management of patients with chronic kidney disease.
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Affiliation(s)
- Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Furkan Yavuz
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey
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19
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Association of MAFLD with end-stage kidney disease: a prospective study of 337,783 UK Biobank participants. Hepatol Int 2023; 17:595-605. [PMID: 36809487 DOI: 10.1007/s12072-023-10486-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 01/12/2023] [Indexed: 02/23/2023]
Abstract
INTRODUCTION Metabolic dysfunction-associated fatty liver (MAFLD) has been found to be associated with the prevalence of chronic kidney disease (CKD). However, it is unknown whether MAFLD is associated with CKD development and the incidence of end-stage kidney disease (ESKD). We aimed to clarify the association between MAFLD and incident ESKD in the prospective UK Biobank cohort. METHODS We analyzed the data of 337,783 UK Biobank participants and relative risks for the ESKD were calculated by using the Cox regression analysis. RESULTS Among 337,783 participants over a median duration of 12.8 years follow-up, a total of 618 ESKD cases were diagnosed. Participants with MAFLD were twice likely to develop ESKD (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.68-2.46, p < 0.001). The association of MAFLD with ESKD risk remained significant in both non-CKD and CKD participants. Our results also showed that there were graded associations between liver fibrosis scores and the risk of ESKD in MAFLD cases. Compared to non-MAFLD individuals, the adjusted HRs for incident ESKD in MAFLD patients with increasing levels of NAFLD fibrosis score were 1.23 (95% CI 0.96-1.58), 2.45 (1.98-3.03) and 7.67 (5.48-10.73), respectively. Furthermore, the risking alleles of PNPLA3 rs738409, TM6SF2 rs58542926, GCKR rs1260326 and MBOAT7 rs641738 amplified the MAFLD effect on ESKD risk. In conclusion, MAFLD is associated with incident ESKD. CONCLUSION MAFLD may help identify the subjects at high risk of ESKD development and MAFLD interventions should be encouraged to slow down CKD progression.
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Nah EH, Shin SK, Cho S, Park H, Kim S, Kwon E, Cho HI. Chronic kidney disease in nonalcoholic fatty liver disease at primary healthcare centers in Korea. PLoS One 2022; 17:e0279367. [PMID: 36538567 PMCID: PMC9767345 DOI: 10.1371/journal.pone.0279367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The prevalence rates of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are expected to increase with the rising trends in diabetes and obesity associated with aging populations. Considering the impacts of coexistent NAFLD and CKD on morbidity and mortality rates, screening strategies for groups at high-risk of CKD are needed in community-dwelling individuals with NAFLD. The aims of this study were to determine the prevalence and distribution of CKD in NAFLD, as well as the risk factors for CKD and the correlation with liver fibrosis in asymptomatic individuals with NAFLD at primary healthcare centers in Korea. METHODS This retrospective cross-sectional study used data from 13 health-promotion centers in 10 Korean cities. Liver steatosis and stiffness were assessed using ultrasonography and magnetic resonance elastography (MRE), respectively. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2, and urine albumin-to-creatinine ratio or proteinuria. CKD was categorized into four stages: no CKD, mild, moderate, and severe. Comparisons according to the CKD stages in NAFLD were performed using Student's t-test or the chi-square test. Multivariable logistic regression analyses were performed to identify the risk factors for CKD and the correlation with liver fibrosis in NAFLD. RESULTS The prevalence of CKD was 12.4% in NAFLD. Albuminuria (16.2%) and proteinuria (8.0%) were more prevalent in NAFLD. NAFLD (odd ratio = 1.27, 95% CI = 1.09-1.48, P = 0.003) was independently associated with CKD of at least mild stage. However, there was no significant association between CKD of at least moderate stage and NAFLD after adjusting for age and a metabolically unhealthy status. CKD was associated with significant liver fibrosis as measured by MRE in NAFLD. CONCLUSION The presence of NAFLD and liver fibrosis were independent risk factors for CKD, but NAFLD was not an independent risk factor for the later stages of CKD.
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Affiliation(s)
- Eun-Hee Nah
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
- * E-mail: ,
| | - Sug Kyun Shin
- Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Seon Cho
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Hyeran Park
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Suyoung Kim
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Eunjoo Kwon
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Han-Ik Cho
- MEDIcheck LAB, Korea Association of Health Promotion, Seoul, Korea
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21
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Han E, Kim MK, Im SS, Jang BK, Kim HS. Non-alcoholic fatty liver disease and sarcopenia is associated with the risk of albuminuria independent of insulin resistance, and obesity. J Diabetes Complications 2022; 36:108253. [PMID: 35817677 DOI: 10.1016/j.jdiacomp.2022.108253] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 06/21/2022] [Accepted: 06/28/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Although non-alcoholic fatty liver disease (NAFLD) is associated with metabolic disorders, its influence on albuminuria has not been determined. The aim of this study was to identify the relationship between NAFLD and albuminuria in the general Korean population. METHODS Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) of 2008-2011 were analyzed (n = 1795). Albuminuria was defined as an albumin-to-creatinine ratio of ≥30 mg/g in random spot urine samples. NAFLD was defined as a fatty liver index (FLI) ≥60 or NAFLD liver fat score (LFS) > -0.64. RESULTS A total of 289 (16.1 %) subjects were classified as having albuminuria. Subjects with NAFLD exhibited a higher rate of albuminuria than subjects without NAFLD (crude odds ratios [ORs] = 2.60-2.95, all P < 0.001). Regardless of hypertension, insulin resistance, or obesity, the risk for albuminuria was higher in the NAFLD group than in the group without NAFLD (measured by either FLI or LFS; all P < 0.001). When subjects with NAFLD had sarcopenia, the risk of albuminuria further increased (OR = 4.33-4.64, all P < 0.001). Multiple logistic regression analyses also demonstrated that NAFLD was independently associated with albuminuria (OR = 2.58, 95 % confidence interval [CI] = 1.66-4.02, P < 0.001 for FLI, OR = 1.87, 95 % CI = 1.28-2.75, P = 0.001 for LFS). CONCLUSIONS NAFLD was associated with an increased risk of albuminuria in the general Korean population. This association was independent of hypertension, insulin resistance, chronic kidney disease, diabetes and obesity, and stronger in subjects with sarcopenia.
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Affiliation(s)
- Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Mi Kyung Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Seung-Soon Im
- Department of Physiology, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Hye Soon Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
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22
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Sharma S, Stine JG, Verbeek T, Bezinover D. Management of Patients With Non-alcoholic Steatohepatitis Undergoing Liver Transplantation: Considerations for the Anesthesiologist. J Cardiothorac Vasc Anesth 2022; 36:2616-2627. [PMID: 34391652 DOI: 10.1053/j.jvca.2021.07.020] [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: 04/21/2021] [Revised: 06/24/2021] [Accepted: 07/09/2021] [Indexed: 11/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA.
| | - Jonathan G Stine
- Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA; Department of Medicine and Public Health Sciences, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Cancer Institute, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA
| | - Thomas Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA
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23
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Sharma N, Sircar A, Anders HJ, Gaikwad AB. Crosstalk between kidney and liver in non-alcoholic fatty liver disease: mechanisms and therapeutic approaches. Arch Physiol Biochem 2022; 128:1024-1038. [PMID: 32223569 DOI: 10.1080/13813455.2020.1745851] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver and kidney are vital organs that maintain homeostasis and injury to either of them triggers pathogenic pathways affecting the other. For example, non-alcoholic fatty liver disease (NAFLD) promotes the progression of chronic kidney disease (CKD), vice versa acute kidney injury (AKI) endorses the induction and progression of liver dysfunction. Progress in clinical and basic research suggest a role of excessive fructose intake, insulin resistance, inflammatory cytokines production, activation of the renin-angiotensin system, redox imbalance, and their impact on epigenetic regulation of gene expression in this context. Recent developments in experimental and clinical research have identified several biochemical and molecular pathways for AKI-liver interaction, including altered liver enzymes profile, metabolic acidosis, oxidative stress, activation of inflammatory and regulated cell death pathways. This review focuses on the current preclinical and clinical findings on kidney-liver crosstalk in NAFLD-CKD and AKI-liver dysfunction settings and highlights potential molecular mechanisms and therapeutic targets.
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Affiliation(s)
- Nisha Sharma
- Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, Rajasthan, India
| | - Anannya Sircar
- Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, Rajasthan, India
| | - Hans-Joachim Anders
- Division of Nephrology, Department of Internal Medicine IV, University Hospital of the Ludwig Maximilians University Munich, Munich, Germany
| | - Anil Bhanudas Gaikwad
- Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, Rajasthan, India
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Mikolasevic I, Domislovic V, Ruzic A, Hauser G, Rahelic D, Klobucar-Majanovic S, Krznaric Z, Dobrila-Dintinjana R, Grgurevic I, Skenderevic N, Lukic A, Targher G. Elastographic parameters of liver steatosis and fibrosis predict independently the risk of incident chronic kidney disease and acute myocardial infarction in patients with type 2 diabetes mellitus. J Diabetes Complications 2022; 36:108226. [PMID: 35803839 DOI: 10.1016/j.jdiacomp.2022.108226] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 05/11/2022] [Accepted: 05/30/2022] [Indexed: 11/15/2022]
Abstract
AIMS The aim of this prospective study was to examine the relationship between controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) with the risk of developing a composite endpoint inclusive of incident acute myocardial infarction (AMI), cerebrovascular insult (CVI) or chronic kidney disease (CKD) in people with type 2 diabetes mellitus (T2DM). METHODS This study included 238 T2DM outpatients without chronic liver diseases. RESULTS The patient population was followed for a median period of 7.6 years. Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the aforementioned composite outcome (P < 0.001 by the log-rank test), as well as CKD (P < 0.001) or AMI alone (P = 0.014) among those with elevated CAP values (≥238 dB/m) at baseline. Similarly, Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the composite outcome (P < 0.001), as well as CKD (P < 0.001), or AMI alone (P < 0.001) among those with elevated LSM values (≥7.0/6.2 kPa). In multivariable regression analyses, the presence of elevated CAP (adjusted-hazard ratio 2.34, 95% CI 1.32-4.15) and elevated LSM (adjusted-hazard ratio 2.84, 95% CI 1.92-4.21), independently of each other, were associated with a higher risk of developing the composite outcome, as well as incident AMI or CKD alone after adjusting for traditional cardiovascular risk factors and diabetes-related variables. CONCLUSIONS Our study shows that the elastographic parameters of liver steatosis and fibrosis independently predict the long-term risk of developing chronic vascular complications in T2DM patients.
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Affiliation(s)
- I Mikolasevic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia; Faculty of Medicine, Rijeka, Croatia.
| | - V Domislovic
- Department for Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia
| | - A Ruzic
- Faculty of Medicine, Rijeka, Croatia; Clinic for Cardiology, University Hospital Center Rijeka, Rijeka, Croatia
| | - G Hauser
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia; Faculty of Medicine, Rijeka, Croatia; Faculty of Health Studies, Rijeka, Croatia
| | - D Rahelic
- Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia; University of Zagreb Faculty of Medicine, Zagreb, Croatia; University of Osijek Faculty of Medicine, Osijek, Croatia
| | - S Klobucar-Majanovic
- Faculty of Medicine, Rijeka, Croatia; Department for Diabetes, Endocrinology and Metabolic Diseases, UHC Rijeka, Croatia
| | - Z Krznaric
- Department for Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia; University of Zagreb Faculty of Medicine, Zagreb, Croatia
| | - R Dobrila-Dintinjana
- Faculty of Medicine, Rijeka, Croatia; Department of Oncology, UHC Rijeka, Croatia
| | - I Grgurevic
- University of Zagreb Faculty of Medicine, Zagreb, Croatia; Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb, Croatia
| | - N Skenderevic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia
| | - A Lukic
- Department of Gastroenterology, University Hospital Center Rijeka, Rijeka, Croatia
| | - G Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Italy
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25
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Tapper EB, Fleming C, Rendon A, Fernandes J, Johansen P, Augusto M, Nair S. The Burden of Nonalcoholic Steatohepatitis: A Systematic Review of Epidemiology Studies. GASTRO HEP ADVANCES 2022; 1:1049-1087. [PMID: 39131247 PMCID: PMC11307414 DOI: 10.1016/j.gastha.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/30/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Nonalcoholic steatohepatitis (NASH) is associated with increased mortality and risk of complications but is often asymptomatic and under-recognized. A systematic review of NASH epidemiology was conducted to provide information on the burden of NASH and highlight important evidence gaps for future research. Methods Medline, EMBASE, and Cochrane Library databases were searched for English-language publications published from 2010 to January 2022 that reported on natural history, risk factors, comorbidities, and complications of a NASH population or subpopulation. Results Overall, 173 publications were included. NASH was shown to have a variable disease course and high prevalence of comorbid disease. Although many patients progressed to cirrhosis and end-stage liver disease, disease regression or resolution was reported in up to half of patients in some studies. Reported risk factors for disease progression or resolution included levels of (or changes in) serum fibrosis markers, liver enzymes, and platelets. The presence of NASH increased the risk of liver cirrhosis and other serious diseases such as hepatocellular carcinoma, colorectal cancer, chronic kidney disease, and cardiovascular disease. In 2017, NASH was responsible for ∼118,000 cirrhosis deaths globally, and an increasing proportion of patients are receiving liver transplantation for NASH in Europe and the United States. Consolidation of data was hampered by heterogeneity across the studies in terms of patient populations, follow-up time, and outcomes measured. Conclusion NASH is associated with significant morbidity and mortality, an increased risk of comorbidities, and imposes an increasing burden among liver transplantation recipients. Longer studies with harmonized study criteria are required to better understand the impact of NASH on patient outcomes.
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Affiliation(s)
- Elliot B. Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Adriana Rendon
- Global Medical Affairs, Novo Nordisk A/S, Søborg, Denmark
| | - João Fernandes
- Payer Evidence Generation, Novo Nordisk A/S, Søborg, Denmark
| | - Pierre Johansen
- Novo Nordisk Denmark A/S, Region North & West Europe, Ørestad, Denmark
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Han AL, Lee HK. Association of the Metabolic Dysfunction-Associated Fatty Liver Disease with Serum Uric Acid-to-Creatinine Ratio. Metab Syndr Relat Disord 2022; 20:370-376. [PMID: 35796698 DOI: 10.1089/met.2022.0013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: No study has examined whether serum uric acid/creatinine (sUA/Cr) is associated with the newly defined metabolic-associated fatty liver disease (MAFLDs). Furthermore, studies on other factors influencing their relationship have not been conducted. Aim: To investigate the relationship between sUA/Cr and newly defined MAFLD, and to identify any factors that affect this relationship. Methods: We retrospectively reviewed the data of patients who underwent abdominal computed tomography (CT) at the Hospital Health Promotion Center. Participants were divided into the healthy (no evidence of liver disease; n = 707), MAFLD+non-heavy drinking (steatosis diagnosed by CT and drinking <140 and 70 grams/week for men and women, respectively; n = 291), and MAFLD+heavy drinking (fatty liver diagnosed by CT and drinking >140 and 70 grams/week for men and women, respectively; n = 61) groups. The relationship between sUA/Cr and MAFLD among the three groups were compared using multivariate logistic regression. Results: After adjusting for age, it was observed that when the sUA/Cr ratio increased by 1, the risk of MAFLD increased by 1.205 times the risk in the normal group. After adjusting for age, an increase by 1 in the sUA/Cr ratio increased the probability of non-heavy drinking+MAFLD and heavy drinking+MAFLD by 1.302 and 1.556 times, respectively, compared with healthy individuals. For those who smoked, the probability of heavy drinking+MAFLD was 9.901 times higher compared with healthy individuals. Conclusion: The newly defined MAFLD is related to sUA/Cr. The amount of alcohol consumption and smoking influenced the association between sUA/Cr and MAFLD.
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Affiliation(s)
- A Lum Han
- Department of Family Medicine, Wonkwang University Hospital, Iksan, Republic of Korea
| | - Hee Kyung Lee
- Department of Family Medicine, Wonkwang University Hospital, Iksan, Republic of Korea
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27
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Seo DH, Suh YJ, Cho Y, Ahn SH, Seo S, Hong S, Lee YH, Choi YJ, Lee E, Kim SH. Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease. Diabetes Metab J 2022; 46:630-639. [PMID: 35081304 PMCID: PMC9353562 DOI: 10.4093/dmj.2021.0130] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 10/24/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM. METHODS In this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS At baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3±3.6 years, 472 (14.8%) patients developed incident CKD: 220 (15.1%) in the non-NAFLD group, 231 (14.1%) in the NAFLD without advanced fibrosis group and 28 (31.1%) in the NAFLD with advanced fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared to the non-NAFLD group (P=0.435). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; P=0.009). CONCLUSION Advanced liver fibrosis in patients with NAFLD is independently associated with an increased risk of incident CKD in patients with T2DM.
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Affiliation(s)
- Da Hea Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
| | - Young Ju Suh
- Department of Biomedical Sciences, Inha University College of Medicine, Incheon, Korea
| | - Yongin Cho
- 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
| | - Seongha Seo
- 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
| | - Yong-ho Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | | | - Eunjig Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - So Hun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea
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Han E. Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease. Diabetes Metab J 2022; 46:564-566. [PMID: 35929174 PMCID: PMC9353564 DOI: 10.4093/dmj.2022.0203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Affiliation(s)
- Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
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29
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Duell PB, Welty FK, Miller M, Chait A, Hammond G, Ahmad Z, Cohen DE, Horton JD, Pressman GS, Toth PP. Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol 2022; 42:e168-e185. [PMID: 35418240 DOI: 10.1161/atv.0000000000000153] [Citation(s) in RCA: 325] [Impact Index Per Article: 108.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.
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30
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Jung CY, Ryu GW, Kim HW, Ahn SH, Kim SU, Kim BS. Advanced liver fibrosis measured by transient elastography predicts chronic kidney disease development in individuals with non-alcoholic fatty liver disease. Diabetologia 2022; 65:518-527. [PMID: 34932136 DOI: 10.1007/s00125-021-05627-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/05/2021] [Indexed: 12/19/2022]
Abstract
AIMS/HYPOTHESIS Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are progressive chronic conditions that share important cardiometabolic risk factors and pathogenic mechanisms. We investigated the association between liver fibrosis measured by transient elastography (TE) and the risk of incident CKD in individuals with NAFLD. METHODS A total of 5983 participants with NAFLD (defined as controlled attenuation parameter >222 dB/m) but without CKD who underwent TE between March 2012 and August 2018 were selected. The primary outcome was incident CKD, defined as the occurrence of eGFR <60 ml min-1 [1.73 m]-2 or proteinuria (≥1+ on dipstick test) on two consecutive measurements during follow-up. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. RESULTS The mean age was 51.8 years and 3756 (62.8%) participants were male. During 17,801 person-years of follow-up (mean follow-up of 3.0 years), 62 participants (1.0%) developed incident CKD. When stratified into TE-defined fibrosis stages (F0-F4), multivariable Cox models revealed that risk of incident CKD was 5.40-fold (95% CI 2.46, 11.84; p < 0.001) higher in the F3/F4 group (≥9.5 kPa) than in the F0 group (<5.5 kPa). During 17,577 person-years of follow-up (mean follow-up of 3.0 years), 201 participants (3.4%) experienced the secondary outcome, for which the F3/F4 group had a 3.22-fold higher risk (95% CI 1.96, 5.28; p < 0.001) than the F0 group. CONCLUSIONS/INTERPRETATION In this large cohort of individuals with NAFLD but without baseline CKD, advanced liver fibrosis measured by TE was significantly associated with a higher risk of incident CKD.
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Affiliation(s)
- Chan-Young Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Geun Woo Ryu
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University, College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University, College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
| | - Beom Seok Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
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31
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Tao Z, Li Y, Cheng B, Zhou T, Gao Y. Influence of Nonalcoholic Fatty Liver Disease on the Occurrence and Severity of Chronic Kidney Disease. J Clin Transl Hepatol 2022; 10:164-173. [PMID: 35233386 PMCID: PMC8845149 DOI: 10.14218/jcth.2021.00171] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/10/2021] [Accepted: 08/25/2021] [Indexed: 12/04/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is reported to affect 20-30% of adults and is accompanied by various metabolic comorbidities, where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases. Chronic kidney disease (CKD), which has a high incidence rate, high morbidity and mortality rates, and high medical costs, has been linked to NAFLD. CKD is associated with some metabolism-related risk factors that overlap with metabolic comorbidities of NAFLD. Therefore, to investigate the potential factors that influence CKD occurrence, the association between NAFLD and CKD should be clarified. Some studies have confirmed that NAFLD influences the occurrence and severity of CKD, whereas some studies have indicated that there is no correlation. In this review, the results of a few studies have been discussed, the potential risk factors for CKD in NAFLD are explored, and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.
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Affiliation(s)
| | | | | | | | - Yanjing Gao
- Correspondence to: Yanjing Gao, Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. ORCID: https://orcid.org/0000-0001-8153-3754. Tel: +86-18560086087, E-mail:
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Martínez-Montoro JI, Kuchay MS, Balaguer-Román A, Martínez-Sánchez MA, Frutos MD, Fernández-García JC, Ramos-Molina B. Gut microbiota and related metabolites in the pathogenesis of nonalcoholic steatohepatitis and its resolution after bariatric surgery. Obes Rev 2022; 23:e13367. [PMID: 34729904 DOI: 10.1111/obr.13367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/06/2021] [Accepted: 09/06/2021] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the rising prevalence of obesity, leading to major health and socioeconomic consequences. To date, the most effective therapeutic approach for NAFLD is weight loss. Accordingly, bariatric surgery (BS), which produces marked reductions in body weight, is associated with significant histopathological improvements in advanced stages of NAFLD, such as nonalcoholic steatohepatitis (NASH) and liver fibrosis. BS is also associated with substantial taxonomical and functional alterations in gut microbiota, which are believed to play a significant role in metabolic improvement after BS. Interestingly, gut microbiota and related metabolites may be implicated in the pathogenesis of NAFLD through diverse mechanisms, including specific microbiome signatures, short chain fatty acid production or the modulation of one-carbon metabolism. Moreover, emerging evidence highlights the potential association between gut microbiota changes after BS and NASH resolution. In this review, we summarize the current knowledge on the relationship between NAFLD severity and gut microbiota, as well as the role of the gut microbiome and related metabolites in NAFLD improvement after BS.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain
| | - Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta - The Medicity Hospital, Gurugram, Haryana, India
| | - Andrés Balaguer-Román
- Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain.,Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
| | | | - María Dolores Frutos
- Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - José Carlos Fernández-García
- Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain
| | - Bruno Ramos-Molina
- Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
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Muthiah MD, Cheng Han N, Sanyal AJ. A clinical overview of non-alcoholic fatty liver disease: A guide to diagnosis, the clinical features, and complications-What the non-specialist needs to know. Diabetes Obes Metab 2022; 24 Suppl 2:3-14. [PMID: 34387409 DOI: 10.1111/dom.14521] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 07/31/2021] [Accepted: 08/04/2021] [Indexed: 11/29/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has a rapidly rising prevalence worldwide and is the most common cause of liver disease in developed countries. In this article, we discuss the spectrum of disease of NAFLD with a focus on the earlier spectrum of the disease that is commonly encountered by non-specialists, as well as the hepatic and extra-hepatic associations of the disease. We discuss in detail the two common presentations of NAFLD, incidentally detected hepatic steatosis and asymptomatic raised liver enzymes, and provide an algorithm for management and continued to follow up for these patients. Considerations for the management of cardiovascular comorbidities in these patients are also discussed. Finally, we cover the topic of screening for NAFLD in high-risk populations.
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Affiliation(s)
- Mark D Muthiah
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Ng Cheng Han
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
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Giri S, Kasturi S, Darak H. Albumin for AKI in cirrhosis - Sham therapy or effective? Liver Int 2022; 42:258-259. [PMID: 34817914 DOI: 10.1111/liv.15114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 11/19/2021] [Indexed: 02/13/2023]
Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Sunil Kasturi
- Gastrocare, Liver and Digestive Disease Center, Bhopal, India
| | - Harish Darak
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
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35
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Zarghamravanbakhsh P, Frenkel M, Poretsky L. Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD). Metabol Open 2021; 12:100149. [PMID: 34870138 PMCID: PMC8626571 DOI: 10.1016/j.metop.2021.100149] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/10/2021] [Accepted: 11/10/2021] [Indexed: 12/11/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that was first described in 1980. It has been prevalent and on the rise for many years and is associated with other metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). NAFLD can be best described as a metabolic dysfunction that stems from insulin resistance-induced hepatic lipogenesis. This lipogenesis increases oxidative stress and hepatic inflammation and is often potentiated by genetic and gut microbiome dysfunction. As NAFLD progresses from simple steatosis to non-alcoholic steatohepatitis (NASH) and to cirrhosis and hepatocellular carcinoma (HCC), the odds of complications including cardiovascular disease (CVD), chronic kidney disease (CKD), and overall mortality increase. The aim of this review is to describe the metabolic causes and consequences of NAFLD while examining the risks that each stage of NAFLD poses. In this review, the etiology of "lean" NAFLD, the impact of obesity, T2DM, genetics, and microbiome dysbiosis on NAFLD progression are all explored. This review will also discuss the core issue behind the progression of NAFLD: insulin resistance (IR). Upon describing the causes and consequences of NAFLD, the effectiveness of diet modification, lifestyle changes, and glucagon-like peptide 1 receptor (GLP-1) agonists to retard NAFLD progression and stem the rate of complications is examined.
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Affiliation(s)
- Paria Zarghamravanbakhsh
- Division of Endocrinology, Department of Medicine, Lenox Hill Hospital, Northwell Health, 110 East 59th St #8B, New York, NY, 10022, USA
| | - Michael Frenkel
- The Gerald J. Friedman Diabetes Institute, Northwell Health, 110 East 59th St #8B, New York, NY, 10022, USA
| | - Leonid Poretsky
- Division of Endocrinology, Department of Medicine, Lenox Hill Hospital, Northwell Health, 110 East 59th St #8B, New York, NY, 10022, USA
- The Gerald J. Friedman Diabetes Institute, Northwell Health, 110 East 59th St #8B, New York, NY, 10022, USA
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Wu Y, Chen Z, Fuda H, Tsukui T, Wu X, Shen N, Saito N, Chiba H, Hui SP. Oxidative Stress Linked Organ Lipid Hydroperoxidation and Dysregulation in Mouse Model of Nonalcoholic Steatohepatitis: Revealed by Lipidomic Profiling of Liver and Kidney. Antioxidants (Basel) 2021; 10:1602. [PMID: 34679736 PMCID: PMC8533338 DOI: 10.3390/antiox10101602] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/05/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is a prevalent disease related to lipid metabolism disorder and oxidative stress. Lipid hydroperoxidation is known to be a critical driving force of various disorders and diseases. However, the combination of both intact and hydroperoxidized lipids in NASH has not yet been studied. In this work, the liver and kidney samples from NASH-model mice were comprehensively investigated by using the LC/MS-based lipidomic analysis. As a result, triglycerides showed the amount accumulation and the profile alteration for the intact lipids in the NASH group, while phosphatidylethanolamines, lysophosphatidylethanolamines, plasmalogens, and cardiolipins largely depleted, suggesting biomembrane damage and mitochondria dysfunction. Notably, the lipid hydroperoxide species of triglyceride and phosphatidylcholine exhibited a significant elevation in both the liver and the kidney of the NASH group and showed considerable diagnostic ability. Furthermore, the relationship was revealed between the lipid metabolism disturbance and the lipid hydroperoxide accumulation, which played a key role in the vicious circle of NASH. The present study suggested that the omics approach to the lipid hydroperoxide profile might be the potential diagnostic marker of NASH and other oxidative stress-related diseases, as well as the evaluative treatment index of antioxidants.
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Affiliation(s)
- Yue Wu
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
| | - Zhen Chen
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
| | - Hirotoshi Fuda
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
| | - Takayuki Tsukui
- Department of Nutrition, Sapporo University of Health Sciences, Nakanuma Nishi-4-2-1-15, Higashi-Ku, Sapporo 007-0894, Japan; (T.T.); (H.C.)
| | - Xunzhi Wu
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
| | - Nianqiu Shen
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
| | - Natsuki Saito
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
| | - Hitoshi Chiba
- Department of Nutrition, Sapporo University of Health Sciences, Nakanuma Nishi-4-2-1-15, Higashi-Ku, Sapporo 007-0894, Japan; (T.T.); (H.C.)
| | - Shu-Ping Hui
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-Ku, Sapporo 060-0812, Japan; (Y.W.); (Z.C.); (H.F.); (X.W.); (N.S.); (N.S.)
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Zuo G, Xuan L, Xin Z, Xu Y, Lu J, Chen Y, Dai M, Zhang D, Wang W, Li M, Bi Y, Ning G, Xu M. New Nonalcoholic Fatty Liver Disease and Fibrosis Progression Associate With the Risk of Incident Chronic Kidney Disease. J Clin Endocrinol Metab 2021; 106:e3957-e3968. [PMID: 34125886 DOI: 10.1210/clinem/dgab425] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Indexed: 02/07/2023]
Abstract
CONTEXT Little is known about the link between nonalcoholic fatty liver disease (NAFLD) evolution and incident chronic kidney disease (CKD). OBJECTIVE We aim to assess the associations of NALFD status changes and NAFLD fibrosis progression with the risk of incident CKD. METHODS We conducted a community-based prospective study that included participants aged 40 years or older and free of CKD at baseline in 2010, with follow-up evaluations after a mean of 4.4 years. NAFLD was diagnosed by ultrasonography and NAFLD fibrosis score (NFS) was used to evaluate fibrosis stage and progression. CKD was defined by estimated glomerular filtration rate or urine albumin-to-creatinine ratio. All the measurements were performed at baseline and follow-up examination. RESULTS Among 4042 participants with 4 NAFLD status change groups, incident NAFLD was associated with an increased risk of incident CKD (odds ratio [OR] = 1.44; 95% CI, 1.003-2.06; P = 0.048) compared with non-NAFLD after adjustments for the confounders, including evolution of diabetes, hypertension, and obesity, in addition to the baseline levels. However, the risk of incident CKD was not significantly different between NAFLD resolution and persistent NAFLD. Among 534 participants in the persistent NAFLD group, fibrosis progression from low NFS to intermediate or high NFS was associated with a significantly increased risk of incident CKD compared with stable fibrosis in low NFS (OR = 2.82; 95% CI, 1.22-6.56; P = 0.016). CONCLUSION NAFLD development and fibrosis progression are associated with increased risk of incident CKD.
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Affiliation(s)
- Guangmin Zuo
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liping Xuan
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhuojun Xin
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Meng Dai
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Di Zhang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Heda R, Yazawa M, Shi M, Bhaskaran M, Aloor FZ, Thuluvath PJ, Satapathy SK. Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect. World J Gastroenterol 2021; 27:1864-1882. [PMID: 34007127 PMCID: PMC8108029 DOI: 10.3748/wjg.v27.i17.1864] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/07/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
With the growing prevalence of obesity and diabetes in the United States and across the world, a rise in the overall incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is expected. The risk factors for NAFLD are also associated with the development of chronic kidney disease (CKD). We review the epidemiology, risk factors, genetics, implications of gut dysbiosis, and specific pathogenic mechanisms linking NAFLD to CKD. Mechanisms such as ectopic lipid accumulation, cellular signaling abnormalities, and the interplay between fructose consumption and uric acid accumulation have led to the emergence of potential therapeutic implications for this patient population. Transplant evaluation in the setting of both NAFLD and CKD is also reviewed. Potential strategies for surveillance and management include the monitoring of comorbidities, the use of non-invasive fibrosis scoring systems, and the measurement of laboratory markers. Lastly, we discuss the management of patients with NAFLD and CKD, from preventative measures to experimental interventions.
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Affiliation(s)
- Rajiv Heda
- Department of Internal Medicine, Tulane University School of Medicine, New Orleans, LA 70112, United States
| | - Masahiko Yazawa
- Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan
| | - Michelle Shi
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, United States
| | - Madhu Bhaskaran
- Department of Nephrology, Northwell Health/Zucker School of Medicine at Hosftra, Manhasset, NY 11030, United States
| | - Fuad Zain Aloor
- Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030, United States
| | - Paul J Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, MD 21202, United States
| | - Sanjaya K Satapathy
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, United States
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Arora A, Kumar A, Prasad N, Duseja A, Acharya SK, Agarwal SK, Aggarwal R, Anand AC, Bhalla AK, Choudhary NS, Chawla YK, Dhiman RK, Dixit VK, Gopalakrishnan N, Gupta A, Hegde UN, Jasuja S, Jha V, Kher V, Kumar A, Madan K, Maiwall R, Mathur RP, Nayak SL, Pandey G, Pandey R, Puri P, Rai RR, Raju SB, Rana DS, Rao PN, Rathi M, Saraswat VA, Saxena S, Shalimar, Sharma P, Singh SP, Singal AK, Soin AS, Taneja S, Varughese S. INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease. J Clin Exp Hepatol 2021; 11:354-386. [PMID: 33994718 PMCID: PMC8103529 DOI: 10.1016/j.jceh.2020.09.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 09/27/2020] [Indexed: 01/10/2023] Open
Abstract
Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.
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Affiliation(s)
- Anil Arora
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
| | - Subrat K. Acharya
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Sanjay K. Agarwal
- Department of Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, Delhi, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Anil K. Bhalla
- Department of Nephrology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta -The Medicity, CH Baktawar Singh Rd, Sector 38, Gurugram, 122001, Haryana, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India
| | | | - Ashwani Gupta
- Department of Nephrology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Umapati N. Hegde
- Department of Nephrology, Muljibhai Patel Urological Hospital, Dr VV Desai Road, Nadiad, 387001, Gujarat, India
| | - Sanjiv Jasuja
- Department of Nephrology, Indraprastha Apollo Hospital, Mathura Road, Sarita Vihar, New Delhi, 110076, India
| | - Vivek Jha
- The George Institute for Global Health, Elegance Tower, 311-312, Third Floor, Jasola Vihar, New Delhi, 110025, Delhi, India
| | - Vijay Kher
- Nephrology, Medanta Kidney & Urology Institute, Medanta -The Medicity, CH Baktawar Singh Rd, Sector 38, Gurugram, 122001, Haryana, India
| | - Ajay Kumar
- Institute for Digestive & Liver Diseases, BLK Hospital, Pusa Road, Radha Soami Satsang, Rajendra Place, New Delhi, 110005, Delhi, India
| | - Kaushal Madan
- Max Smart Super Specialty Hospital, Saket, New Delhi, 110017, Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver & Biliary Sciences, D1, Vasant Kunj, New Delhi, 110070, Delhi, India
| | - Rajendra P. Mathur
- Department of Nephrology, Institute of Liver & Biliary Sciences, D1, Vasant Kunj, New Delhi, 110070, Delhi, India
| | - Suman L. Nayak
- Dharamshila Narayana Superspeciality Hospital, New Delhi, 110096, Delhi, India
| | - Gaurav Pandey
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Rajendra Pandey
- Department of Nephrology, Institute of Post Graduate Medical Education & Research, 244, Acharya Jagadish Chandra Bose Road, Bhowanipore, Kolkata, 700020, West Bengal, India
| | - Pankaj Puri
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Ramesh R. Rai
- Rai Specialty Center, H-6, Jan Path, Near DANA-PANI Restaurant, Kishan Nagar, Shyam Nagar, Jaipur, 302019, Rajasthan, India
| | - Sree B. Raju
- Department of Nephrology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, 500082, Telangana, India
| | - Devinder S. Rana
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, 110060, Delhi, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, 500082, Telangana, India
| | - Manish Rathi
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India
| | - Sanjiv Saxena
- Institute of Renal Sciences, PSRI Hospital, Press Enclave Marg, J Pocket, Phase II, Sheikh Sarai, New Delhi, 110017, Delhi, India
| | - Shalimar
- Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Shivaram P. Singh
- Department of Gastroenterology, S.C.B. Medical College, Cuttack 753007, Odisha, India
| | - Ashwani K. Singal
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD 57105, USA
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta -The Medicity, CH Baktawar Singh Rd, Sector 38, Gurugram, 122001, Haryana, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
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Sjöstedt N, Neuhoff S, Brouwer KL. Physiologically-Based Pharmacokinetic Model of Morphine and Morphine-3-Glucuronide in Nonalcoholic Steatohepatitis. Clin Pharmacol Ther 2021; 109:676-687. [PMID: 32897538 PMCID: PMC7902445 DOI: 10.1002/cpt.2037] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/19/2020] [Indexed: 01/17/2023]
Abstract
Nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, is increasing in prevalence. NASH-related alterations in hepatic protein expression (e.g., transporters) and in overall physiology may affect drug exposure by altering drug disposition and elimination. The aim of this study was to build a physiologically-based pharmacokinetic (PBPK) model to predict drug exposure in NASH by incorporating NASH-related changes in hepatic transporters. Morphine and morphine-3-glucuronide (M3G) were used as model compounds. A PBPK model of morphine with permeability-limited hepatic disposition was extended to include M3G disposition and enterohepatic recycling (EHR). The model captured the area under the plasma concentration-time curve (AUC) of morphine and M3G after intravenous morphine administration within 0.82-fold and 1.94-fold of observed values from 3 independent clinical studies for healthy adult subjects (6, 10, and 14 individuals). When NASH-related changes in multidrug resistance-associated protein 2 (MRP2) and MRP3 were incorporated into the model, the predicted M3G mean AUC in NASH was 1.34-fold higher compared to healthy subjects, which is slightly lower than the observed value (1.63-fold). Exploratory simulations on other physiological changes occurring in NASH (e.g., moderate decreases in glomerular filtration rate and portal vein blood flow) revealed that the effect of transporter changes was most prominent. Additionally, NASH-related transporter changes resulted in decreased morphine EHR, which could be important for drugs with extensive EHR. This study is an important first step to predict drug disposition in complex diseases such as NASH using PBPK modeling.
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Affiliation(s)
- Noora Sjöstedt
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC (N.S., K.L.R.B.); Certara UK Ltd, Simcyp-Division, Sheffield, UK (S.N.)
| | - Sibylle Neuhoff
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC (N.S., K.L.R.B.); Certara UK Ltd, Simcyp-Division, Sheffield, UK (S.N.)
| | - Kim L.R. Brouwer
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC (N.S., K.L.R.B.); Certara UK Ltd, Simcyp-Division, Sheffield, UK (S.N.)
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Balakrishnan M, Patel P, Dunn-Valadez S, Dao C, Khan V, Ali H, El-Serag L, Hernaez R, Sisson A, Thrift AP, Liu Y, El-Serag HB, Kanwal F. Women Have a Lower Risk of Nonalcoholic Fatty Liver Disease but a Higher Risk of Progression vs Men: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2021; 19:61-71.e15. [PMID: 32360810 PMCID: PMC8796200 DOI: 10.1016/j.cgh.2020.04.067] [Citation(s) in RCA: 178] [Impact Index Per Article: 44.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/16/2020] [Accepted: 04/04/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis. METHODS Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome. RESULTS Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD analysis, 5428 for the NASH analysis, and 6444 for the advanced fibrosis analysis. Women had a 19% lower risk of NAFLD than men in the general population (pooled risk ratio [RR], 0.81; 95% CI, 0.68-0.97; I2 = 97.5%). Women had a similar risk of NASH (RR, 1.00; 95% CI, 0.88-1.14; I2 = 85.1%), and a 37% higher risk of advanced fibrosis (RR, 1.37; 95% CI, 1.12-1.68; I2 = 74.0%) than men. Age modified the effect of sex on NAFLD severity. Risks of NASH (RR, 1.17; 95% CI, 1.01-1.36) and advanced fibrosis (RR, 1.56; 95% CI, 1.36-1.80; I2 = 0) were substantially higher in women in study populations with average ages of 50 years and older; sex differences in NASH and advanced fibrosis were attenuated in younger populations. CONCLUSIONS In a systematic review and meta-analysis, we found women to have a lower risk of NAFLD than men. However, once NAFLD is established, women have a higher risk of advanced fibrosis than men, especially after age 50 years.
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Affiliation(s)
| | - Parth Patel
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Sydney Dunn-Valadez
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Cecilia Dao
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Vinshi Khan
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Hiba Ali
- Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Laith El-Serag
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Ruben Hernaez
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Amy Sisson
- Houston Academy of Medicine Texas Medical Center Library, Houston, Texas, USA
| | - Aaron P. Thrift
- Section of Epidemiology & Population, Baylor College of Medicine Department of Medicine, Houston, Texas, USA,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Yan Liu
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA,Department of Internal Medicine, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Hashem B. El-Serag
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA,Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA,Department of Internal Medicine, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Fasiha Kanwal
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Baylor College of Medicine, Houston, Texas, USA,Department of Internal Medicine, Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
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Mertens J, Van Gaal LF, Francque SM, De Block C. NAFLD in type 1 diabetes: overrated or underappreciated? Ther Adv Endocrinol Metab 2021; 12:20420188211055557. [PMID: 34840719 PMCID: PMC8613893 DOI: 10.1177/20420188211055557] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 10/04/2021] [Indexed: 12/18/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries, affecting 25-30% of the general population and up to 65% in those with obesity and/or type 2 diabetes. Accumulation of visceral adipose tissue and insulin resistance (IR) contributes to NAFLD. NAFLD is not an innocent entity as it not only may cause nonalcoholic steatohepatitis and cirrhosis but also contribute to cardiovascular morbidity and mortality. More and more people with type 1 diabetes (T1D) are becoming overweight and present with features of IR, but the prevalence and impact of NAFLD in this population are still unclear. The utility of noninvasive screening tools for NAFLD in T1D is being explored. Recent data indicate that based upon ultrasonographic criteria NAFLD is present in 27% (ranging between 19% and 31%) of adults with T1D. Magnetic resonance imaging data indicate a prevalence rate of 8.6% (ranging between 2.1% and 18.6%). There are, however, multiple factors affecting these data, ranging from study design and referral bias to discrepancies in between diagnostic modalities. Individuals with T1D have a 7-fold higher risk of cardiovascular disease (CVD) and cardiovascular mortality is the most prominent cause of death in T1D. Patients with T1D and NALFD are also more prone to develop CVD, but the independent contribution of NAFLD to cardiovascular events has to be determined in this population. Furthermore, limited data in T1D also point towards a 2 to 3 times higher risk for microvascular complications in those with NAFLD. In this article, we will discuss epidemiological and diagnostic challenges of NAFLD in T1D, explore the link between IR and NAFLD and chronic complications, and examine the independent contribution of NAFLD to the presence of macro-, and microvascular complications.
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Affiliation(s)
- Jonathan Mertens
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Luc F. Van Gaal
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Sven M. Francque
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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Eguchi Y, Wong G, Lee IH, Akhtar O, Lopes R, Sumida Y. Hepatocellular carcinoma and other complications of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Japan: A structured review of published works. Hepatol Res 2021; 51:19-30. [PMID: 33091191 DOI: 10.1111/hepr.13583] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/27/2020] [Accepted: 09/08/2020] [Indexed: 02/08/2023]
Abstract
AIMS Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. METHODS An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria. RESULTS Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%-20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients. CONCLUSION Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.
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Affiliation(s)
- Yuichiro Eguchi
- Liver Center, Saga University Hospital, Saga, Japan.,Department of Internal Medicine, Saga University, Japan
| | | | - I-Heng Lee
- Gilead Sciences Inc, Foster City, CA, USA
| | | | | | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Japan
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Ould Setti M, Voutilainen A, Tuomainen TP. Renal hyperfiltration, fatty liver index, and the hazards of all-cause and cardiovascular mortality in Finnish men. Epidemiol Health 2020; 43:e2021001. [PMID: 33445827 PMCID: PMC7952838 DOI: 10.4178/epih.e2021001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 12/18/2020] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Renal hyperfiltration (RHF) and fatty liver are separately associated with adverse health outcomes. In this study, we investigated the mortality hazard of coexisting RHF and fatty liver. METHODS Middle-aged men from the Kuopio Ischaemic Disease Risk Factor Study (n=1,552) were followed up for a median of 29 years. Associations among RHF, fatty liver index (FLI) score, age, body mass index, smoking status, alcohol consumption, and hypertension status were assessed using logistic regression. Cox proportional hazards models were used to determine the hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality with respect to RHF and fatty liver. RESULTS Of the men, 5% had RHF (n=73), whereas a majority had fatty liver (n=848). RHF was associated specifically with smoking, and fatty liver was associated specifically with overweight. The all-cause mortality hazard was highest (HR, 1.96; 95% confidence interval [CI], 1.27 to 3.01) among men with RHF and fatty liver (n=33). Among men with RHF but normal FLI (n=40), the HR of all-cause mortality was 1.67 (95% CI, 1.15 to 2.42). Among men with fatty liver but a normal estimated glomerular filtration rate (n=527), the HR of all-cause mortality was 1.35 (95% CI, 1.09 to 1.66). CVD mortality hazard was associated with RHF, but not fatty liver. We detected no interaction effect between RHF and fatty liver for all-cause (synergy index, 0.74; 95% CI, 0.21 to 2.67) or CVD (synergy index, 0.94; 95% CI, 0.34 to 2.60) mortality. CONCLUSIONS RHF and fatty liver are independently associated with all-cause and CVD mortality
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Affiliation(s)
- Mounir Ould Setti
- Department of Public Health, University of Eastern Finland, Kuopio, Finland
| | - Ari Voutilainen
- Department of Public Health, University of Eastern Finland, Kuopio, Finland
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Tomeno W, Imajo K, Takayanagi T, Ebisawa Y, Seita K, Takimoto T, Honda K, Kobayashi T, Nogami A, Kato T, Honda Y, Kessoku T, Ogawa Y, Kirikoshi H, Sakamoto Y, Yoneda M, Saito S, Nakajima A. Complications of Non-Alcoholic Fatty Liver Disease in Extrahepatic Organs. Diagnostics (Basel) 2020; 10:E912. [PMID: 33171865 PMCID: PMC7695175 DOI: 10.3390/diagnostics10110912] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the largest cause of death among patients with NAFLD is cardiovascular disease followed by extrahepatic malignancies, whereas liver-related mortality is only the third cause of death. Extrahepatic complications of NAFLD include chronic kidney disease, extrahepatic malignancies (such as colorectal cancer), psychological dysfunction, gastroesophageal reflux disease, obstructive sleep apnea syndrome, periodontitis, hypothyroidism, growth hormone deficiency, and polycystic ovarian syndrome. The objective of this narrative review was to summarize recent evidences about extrahepatic complications of NAFLD, with focus on the prevalent/incident risk of such diseases in patients with NAFLD. To date, an appropriate screening method for extrahepatic complications has not yet been determined. Collaborative care with respective experts seems to be necessary for patient management because extrahepatic complications can occur across multiple organs. Further studies are needed to reveal risk profiles at baseline and to determine an appropriate screening method for extrahepatic diseases.
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Affiliation(s)
- Wataru Tomeno
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Takuya Takayanagi
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Yu Ebisawa
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Kosuke Seita
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Tsuneyuki Takimoto
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Kanami Honda
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Asako Nogami
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Takayuki Kato
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Yasushi Honda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Takaomi Kessoku
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Yuji Ogawa
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Hiroyuki Kirikoshi
- Department of Clinical Laboratory, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan;
| | - Yasunari Sakamoto
- Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashikaigancho, Atami-shi, Shizuoka 413-0012, Japan; (W.T.); (T.T.); (Y.E.); (K.S.); (T.T.); (K.H.); (T.K.); (Y.S.)
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; (K.I.); (T.K.); (A.N.); (Y.H.); (T.K.); (Y.O.); (M.Y.); (S.S.)
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Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep 2020; 2:100192. [PMID: 33163950 PMCID: PMC7607500 DOI: 10.1016/j.jhepr.2020.100192] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 08/06/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, de novo malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.
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Key Words
- CKD, chronic kidney disease
- CNI, calcineurin inhibitors
- DM, diabetes mellitus
- DPP-4, dipeptidyl peptidase-4
- ELTR, European Liver Transplant Registry
- ESLD, end-stage liver disease
- GLP1 RAs, glucagon-like peptide-1 receptor agonists
- Graft survival
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- Hypertension
- IRR, incidence rate ratio
- Immunosuppressant
- LT, liver transplant
- MAFLD, metabolic dysfunction-associated fatty liver disease
- Metabolic complication
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- New-onset diabetes after transplantation
- Non-alcoholic fatty liver disease
- Non-alcoholic steatohepatitis
- OR, odds ratio
- Obesity
- Patient survival
- SGLT2, sodium-glucose co-transporter-2
- Solid organ transplantation
- UNOS, United Network for Organ Sharing
- mTORi, mammalian target of rapamycin inhibitors
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
- Corresponding author. Address: Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital. Tel.: +39 0498212892; fax: + 390498217848.
| | - Chiara Becchetti
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital Padua, University of Padua, Padua, Italy
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Schulz M, Tacke F. Identifying High-Risk NASH Patients: What We Know so Far. ACTA ACUST UNITED AC 2020; 12:125-138. [PMID: 32982495 PMCID: PMC7493213 DOI: 10.2147/hmer.s265473] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/24/2020] [Indexed: 12/12/2022]
Abstract
Steatosis is a condition of hepatic fat overload that is associated with overweight and the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease with a global impact on healthcare. A proportion of NAFLD patients develops nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis or hepatocellular carcinoma (HCC). Identifying patients at risk for potentially life-threatening complications is crucial in their prevention, surveillance and treatment. In addition to hepatic disease progression (cirrhosis, portal hypertension, HCC), NAFLD patients are also at risk of cardiovascular and metabolic diseases as well as extrahepatic malignancies. Liver fibrosis is related to morbidity and mortality in NASH patients, and biomarkers, imaging techniques (ultrasound, elastography, MRI) as well as liver biopsy help in diagnosing fibrosis. In this review, we discuss the tools for identifying patients at risk and their reasonable application in clinical routine in order to stratify prevention and treatment of this emerging disease.
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Affiliation(s)
- Marten Schulz
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) Und Campus Charité Mitte (CCM), Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) Und Campus Charité Mitte (CCM), Berlin, Germany
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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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Kaps L, Labenz C, Galle PR, Weinmann-Menke J, Kostev K, Schattenberg JM. Non-alcoholic fatty liver disease increases the risk of incident chronic kidney disease. United European Gastroenterol J 2020; 8:942-948. [PMID: 32698692 DOI: 10.1177/2050640620944098] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease. Its role in the development of extrahepatic co-morbidities is under investigation. The impact of NAFLD on the development of chronic kidney disease (CKD) is incompletely understood. The aim of this study was to explore the potential contribution of NAFLD on CKD in Germany. METHODS The Disease Analyzer Database covering 7.49 million cases in Germany was explored for patients diagnosed with NAFLD between 2000 and 2015 and was matched 1:1 to a cohort without NAFLD. Matching criteria included age, sex, physician, index year and co-diagnoses associated with CKD. The primary outcomes of this study were incidences of CKD and end-stage renal disease. RESULTS A total of 48,057 patients with NAFLD were matched to 48,057 patients without NAFLD. Within 10 years of the index date, 17.1% of patients with NAFLD and 11.6% of patients without NAFLD were diagnosed with CKD (p < 0.001). On Cox regression analysis, NAFLD was significantly associated with the incidence of CKD (hazard ratio (HR) = 1.58, p < 0.001). This association remained significant across different age groups and subgroups such as patients with diabetes mellitus or arterial hypertension. There was no association between NAFLD and emerging dialysis therapy (HR = 1.25, p = 0.245). CONCLUSIONS In this large database analysis in Germany, NAFLD constitutes an independent risk factor for CKD. Patients living with NAFLD should be monitored for a change in kidney function, facilitating therapeutic measures for kidney disease at an early stage.
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Affiliation(s)
- Leonard Kaps
- I. Department of Medicine, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.,Metabolic Liver Research Programme, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Christian Labenz
- I. Department of Medicine, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.,Metabolic Liver Research Programme, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R Galle
- I. Department of Medicine, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.,Metabolic Liver Research Programme, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | - Julia Weinmann-Menke
- I. Department of Medicine, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
| | | | - Jörn M Schattenberg
- I. Department of Medicine, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.,Metabolic Liver Research Programme, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany
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Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone? Int J Mol Sci 2020; 21:ijms21144939. [PMID: 32668632 PMCID: PMC7404115 DOI: 10.3390/ijms21144939] [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: 04/01/2020] [Revised: 06/30/2020] [Accepted: 06/30/2020] [Indexed: 12/17/2022] Open
Abstract
Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.
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