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Amoroso M, Augustin S, Moosmang S, Gashaw I. Non-invasive biomarkers prognostic of decompensation events in NASH cirrhosis: a systematic literature review. J Mol Med (Berl) 2024; 102:841-858. [PMID: 38753041 PMCID: PMC11213726 DOI: 10.1007/s00109-024-02448-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 02/23/2024] [Accepted: 04/17/2024] [Indexed: 06/29/2024]
Abstract
Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it can lead to decompensation events such as ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma (HCC). In addition, an increased risk for cardiovascular events has been demonstrated in patients with NASH. Pharmacological treatments for NASH cirrhosis are not yet available, one of the reasons being the lack in surrogate endpoints available in clinical trials of NASH cirrhosis. The feasibility of non-invasive prognostic biomarkers makes them interesting candidates as possible surrogate endpoints if their change following treatment would result in better outcomes for patients in future clinical trials of NASH cirrhosis. In this systematic literature review, a summary of the available literature on the prognostic performance of non-invasive biomarkers in terms of cardiovascular events, liver-related events, and mortality is outlined. Due to the scarcity of data specific for NASH cirrhosis, this review includes studies on NAFLD whose evaluation focuses on cirrhosis. Our search strategy identified the following non-invasive biomarkers with prognostic value in studies of NASH patients: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), enhanced liver fibrosis (ELF™), BARD (BMI, AST/ALT (alanine aminotransferase) ratio, diabetes), Hepamet Fibrosis Score (HFS), liver enzymes (AST + ALT), alpha-fetoprotein, platelet count, neutrophil to lymphocyte ratio (NLR), Lysyl oxidase-like (LOXL) 2, miR-122, liver stiffness, MEFIB (liver stiffness measured with magnetic resonance elastography (MRE) + FIB-4), and PNPLA3 GG genotype. The aim of the present systematic literature review is to provide the reader with a summary of the non-invasive biomarkers with prognostic value in NASH cirrhosis and give an evaluation of their utility as treatment monitoring biomarkers in future clinical trials.
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Affiliation(s)
| | | | - Sven Moosmang
- Boehringer Ingelheim Pharma GmbH, Ingelheim, Germany
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Cao L, An Y, Liu H, Jiang J, Liu W, Zhou Y, Shi M, Dai W, Lv Y, Zhao Y, Lu Y, Chen L, Xia Y. Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis. BMC Med 2024; 22:101. [PMID: 38448943 PMCID: PMC10919055 DOI: 10.1186/s12916-024-03315-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 02/23/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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Affiliation(s)
- Limin Cao
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Yu An
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Huiyuan Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Jinguo Jiang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wenqi Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yuhan Zhou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Mengyuan Shi
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wei Dai
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanling Lv
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuhong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanhui Lu
- School of Nursing, Peking University, 38 Xueyuan Rd, Haidian District, Beijing, 100191, China.
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China.
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China.
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Yin H, Yan Z, Zhao F. Risk factors of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: Systematic review and meta-analysis. Technol Health Care 2024; 32:3943-3954. [PMID: 39269862 PMCID: PMC11613056 DOI: 10.3233/thc-231331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 04/21/2024] [Indexed: 09/15/2024]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is currently an important chronic liver disease threatening human life and health. OBJECTIVE To investigate the risk factors of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) by systematic review. METHODS We conducted a systematic review and meta-analysis. A systematic search of Chinese and English databases (PubMed, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang database, and VIP database) was performed until June 30, 2023. Studies were included to investigate the risk factors for HCC in patients with NAFLD. Quality evaluation was performed using the Newcastle-Ottawa Literature Quality Evaluation Scale, and then hazard ratios (HRs) for different influencing factors were combined. RESULTS We reviewed the results of 12 high-quality cohort studies involving 738,934 patients with NAFLD and 1,480 developed HCC. A meta-analysis based on a random-effects model showed that advanced age (HR = 1.81, 95% CI: 1.51-2.17), male gender (HR = 2.51, 95% CI: 1.67-3.78), hypertension (HR = 1.87, 95% CI: 1.05-3.33), and diabetes (HR = 2.27, 95% CI: 1.63-3.16) were risk factors for HCC in NAFLD, and the differences were statistically significant. However, there was no statistically significant effect of current smoking (HR = 1.45, 95% CI: 0.72-2.92) and dyslipidemia (HR = 1.03, 95% CI: 0.72-1.47) on HCC incidence in this study. CONCLUSION Age, sex, hypertension and diabetes are risk factors for HCC in NAFLD patients. Diabetic NAFLD patients have a 2.27-fold increased risk of HCC, and health education and intervention for elderly, male, NAFLD patients with diabetes and hypertension need to be strengthened to promote a reduction in the risk of HCC.
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Affiliation(s)
| | | | - Fangcheng Zhao
- Department of Infection, The Second Affiliated Hospital of Dalian Medical University, Liaoning, China
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Bhatt S S, Krishna Kumar J, Laya S, Thakur G, Nune M. Scaffold-mediated liver regeneration: A comprehensive exploration of current advances. J Tissue Eng 2024; 15:20417314241286092. [PMID: 39411269 PMCID: PMC11475092 DOI: 10.1177/20417314241286092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 09/08/2024] [Indexed: 10/19/2024] Open
Abstract
The liver coordinates over 500 biochemical processes crucial for maintaining homeostasis, detoxification, and metabolism. Its specialized cells, arranged in hexagonal lobules, enable it to function as a highly efficient metabolic engine. However, diseases such as cirrhosis, fatty liver disease, and hepatitis present significant global health challenges. Traditional drug development is expensive and often ineffective at predicting human responses, driving interest in advanced in vitro liver models utilizing 3D bioprinting and microfluidics. These models strive to mimic the liver's complex microenvironment, improving drug screening and disease research. Despite its resilience, the liver is vulnerable to chronic illnesses, injuries, and cancers, leading to millions of deaths annually. Organ shortages hinder liver transplantation, highlighting the need for alternative treatments. Tissue engineering, employing polymer-based scaffolds and 3D bioprinting, shows promise. This review examines these innovative strategies, including liver organoids and liver tissue-on-chip technologies, to address the challenges of liver diseases.
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Affiliation(s)
- Supriya Bhatt S
- Manipal Institute of Regenerative Medicine, Bengaluru, India
- Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Jayanthi Krishna Kumar
- Manipal Institute of Regenerative Medicine, Bengaluru, India
- Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shurthi Laya
- Manipal Institute of Regenerative Medicine, Bengaluru, India
- Manipal Academy of Higher Education, Manipal, Karnataka, India
- Department of Biomedical Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Goutam Thakur
- Department of Biomedical Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Manasa Nune
- Manipal Institute of Regenerative Medicine, Bengaluru, India
- Manipal Academy of Higher Education, Manipal, Karnataka, India
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Rodrigues PM, Afonso MB, Simão AL, Islam T, Gaspar MM, O'Rourke CJ, Lewinska M, Andersen JB, Arretxe E, Alonso C, Santos-Laso Á, Izquierdo-Sanchez L, Jimenez-Agüero R, Eizaguirre E, Bujanda L, Pareja MJ, Prip-Buus C, Banales JM, Rodrigues CMP, Castro RE. miR-21-5p promotes NASH-related hepatocarcinogenesis. Liver Int 2023; 43:2256-2274. [PMID: 37534739 DOI: 10.1111/liv.15682] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/03/2023] [Accepted: 07/17/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND AND AIMS The mechanisms governing the progression of non-alcoholic fatty liver disease (NAFLD) towards steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain elusive. Here, we evaluated the role of hsa-miRNA-21-5p in NASH-related hepatocarcinogenesis. METHODS Hepatic hsa-miR-21-5p expression was evaluated in two cohorts of patients with biopsy-proven NAFLD (n = 199) or HCC (n = 366 HCC and n = 11 NAFLD-HCC). Serum/liver metabolomic profiles were correlated with hsa-miR-21-5p in NAFLD obese patients. Wild-type (WT) and Mir21 KO mice were fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks to induce NASH and NASH-HCC, respectively. RESULTS In obese individuals, hsa-miR-21-5p expression increased with NAFLD severity and associated with a hepatic lipotoxic profile. CDAA-fed WT mice displayed increased hepatic mmu-miR-21-5p levels and progressively developed NASH and fibrosis, with livers presenting macroscopically discernible pre-neoplastic nodules, hyperplastic foci and deregulated cancer-related pathways. Mir21 KO mice exhibited peroxisome-proliferator-activated receptor α (PPARα) activation, augmented mitochondrial activity, reduced liver injury and NAS below the threshold for NASH diagnosis, with the pro-inflammatory/fibrogenic milieu reversing to baseline levels. In parallel, Mir21 KO mice displayed reduced number of pre-neoplastic nodules, hepatocyte proliferation and activation of oncogenic signalling, being protected from NASH-associated carcinogenesis. The hsa-miRNA-21-5p/PPARα pathway was similarly deregulated in patients with HCC- or NASH-related HCC, correlating with HCC markers and worse prognosis. CONCLUSIONS Hsa-miR-21-5p is a key inducer of whole-spectrum NAFLD progression, from simple steatosis to NASH and NASH-associated carcinogenesis. The inhibition of hsa-miR-21-5p, leading to a pro-metabolic profile, might constitute an appealing therapeutic approach to ameliorate NASH and prevent progression towards HCC.
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Affiliation(s)
- Pedro M Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Marta B Afonso
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - André L Simão
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Tawhidul Islam
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Maria M Gaspar
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Colm J O'Rourke
- Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Monika Lewinska
- Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jesper B Andersen
- Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Álvaro Santos-Laso
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Laura Izquierdo-Sanchez
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Raúl Jimenez-Agüero
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Emma Eizaguirre
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
| | | | - Carina Prip-Buus
- Université Paris Descartes UMR-S1016, Institut Cochin, Paris, France
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain
- IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Cecília M P Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Rui E Castro
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
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Moghtadaie A, Mahboobi H, Fatemizadeh S, Kamal MA. Emerging role of nanotechnology in treatment of non-alcoholic fatty liver disease (NAFLD). EXCLI JOURNAL 2023; 22:946-974. [PMID: 38023570 PMCID: PMC10630531 DOI: 10.17179/excli2023-6420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 08/29/2023] [Indexed: 12/01/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a prevailing health challenge that requires urgent innovative interventions. This review explores the role of nanotechnology as a promising potential in the treatment of NAFLD. It delineates the limitations of the current management strategies for NAFLD and highlights the new nanotechnology-based treatments including nanoemulsions, liposomes, micelles, polymeric nanoparticles, nanogels, inorganic nanoparticles, and zinc oxide nanoparticles. Despite the optimism surrounding the nanotechnological approach, the review underscores the need to address the limitations such as technical challenges, potential toxicity, and ethical considerations that impede the practical application of nanotechnology in NAFLD management. It advocates for collaborative efforts from researchers, clinicians, ethicists, and policymakers to achieve safe, effective, and equitable nanotechnology-based treatments for NAFLD. See also Figure 1(Fig. 1).
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Affiliation(s)
- Atie Moghtadaie
- Clinical Fellow in Gastroenterology and Hepatology, Digestive Disease Research Institute, Department of Gastroenterology and Hepatology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Mahboobi
- Clinical Fellow in Gastroenterology and Hepatology, Digestive Disease Research Institute, Department of Gastroenterology and Hepatology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Fatemizadeh
- Department of Gastroenterology and Hepatology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, China
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
- Enzymoics, 7 Peterlee place, Hebersham, NSW 2770; Novel Global Community Educational Foundation, Australia
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Netto AM, Kashiwagi NM, Minanni CA, Santos RD, Cesena FY. Adiposity, hepatic steatosis, and metabolic health transitions in people with obesity: Influences of age and sex. Nutr Metab Cardiovasc Dis 2023; 33:1149-1157. [PMID: 37095017 DOI: 10.1016/j.numecd.2023.03.020] [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: 12/12/2022] [Revised: 03/19/2023] [Accepted: 03/27/2023] [Indexed: 04/26/2023]
Abstract
BACKGROUND AND AIMS Metabolically healthy (MHO) and unhealthy obesity (MUO) may be transient conditions. This study aimed to quantify and identify predictive factors of metabolic transitions in obesity, exploring influences of age and sex. METHODS AND RESULTS We retrospectively evaluated adults with obesity who underwent routine health evaluation. In a cross-sectional analysis of 12,118 individuals (80% male, age 44.3 ± 9.9 years), 16.8% had MHO. In a longitudinal evaluation of 4483 participants, 45.2% of individuals with MHO at baseline had dysmetabolism after a median follow-up of 3.0 (IQR 1.8-5.2) years, whereas 13.3% MUO participants became metabolically healthy (MH). Development of hepatic steatosis (HS, ultrasound) was an independent predictor of MHO conversion to dysmetabolism (OR 2.36; 95% CI 1.43, 3.91; p < 0.001), while HS persistence was inversely associated with transition from MUO to MH status (OR 0.63; 95% CI 0.47, 0.83; p = 0.001). Female sex and older age were associated with a lower chance of MUO regression. A 5% increment in body mass index (BMI) over time increased the likelihood of metabolic deterioration by 33% (p = 0.002) in females and 16% (p = 0.018) in males with MHO. A 5% reduction in BMI was associated with a 39% and 66% higher chance of MUO resolution in females and males, respectively (both p < 0.001). CONCLUSION The findings support a pathophysiological role of ectopic fat depots in metabolic transitions in obesity and identify female sex as an aggravating factor for adiposity-induced dysmetabolism, which has implications for personalized medicine.
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Affiliation(s)
- Alvaro M Netto
- Faculdade Israelita de Ciências da Saúde Albert Einstein, Rua Comendador Elias Jafet, 755, São Paulo, SP, 05653-000, Brazil
| | - Nea M Kashiwagi
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil
| | - Carlos A Minanni
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil
| | - Raul D Santos
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil; Heart Institute (InCor), University of São Paulo Medical School Hospital, Av. Dr. Enéas Carvalho de Aguiar, 44, São Paulo, SP, 05403-900, Brazil
| | - Fernando Yue Cesena
- Hospital Israelita Albert Einstein, Av. Brasil, 1085, São Paulo, SP, 01431-000, Brazil.
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Venugopal S, Dhanoa RK, Selvamani TY, Shoukrie SI, Zahra A, Malla J, Selvaraj R, Hamouda RK, Mohammed L. Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients? A Systematic Review. Cureus 2023; 15:e36079. [PMID: 37065332 PMCID: PMC10101195 DOI: 10.7759/cureus.36079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 03/13/2023] [Indexed: 03/14/2023] Open
Abstract
Diabetes is associated with different types of cancers of which hepatocellular carcinoma (HCC) is one among them. In a study comparing patients with diabetes to those who do not have diabetes, it was evident that the risk of HCC is found to increase two-fold in diabetic than that in non-diabetic patients. It is clear that carcinogenesis is advanced due to diabetes in the liver by a variety of mechanisms. We searched PubMed and Google Scholar for articles from 2010 to 2021 that have an association between diabetes, nonalcoholic fatty liver disease (NAFLD), and HCC. For the development of HCC, diabetes is likely related at both the molecular and epidemiological levels. Both diabetes mellitus and hepatic malignancy have the worst impact on mankind socioeconomically. There is a significant relationship between diabetes and HCC independent of alcohol consumption and viral hepatitis. It is noteworthy that not only the elderly but also people of all age groups should monitor their hemoglobin A1C levels. Diet restriction and lifestyle modification can reduce the risk of complications like HCC; the increased physical activity itself can have a major influence on health and can manage comorbidities like diabetes, NAFLD, and HCC.
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Affiliation(s)
- Sathish Venugopal
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ravneet K Dhanoa
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Tharun Yadhav Selvamani
- General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Shoukrie I Shoukrie
- Orthopaedics and Traumatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Anam Zahra
- Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Jyothirmai Malla
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ramaneshwar Selvaraj
- Internal Medicine/Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- General Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ranim K Hamouda
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lubna Mohammed
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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9
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Rusu I, Pirlog R, Chiroi P, Nutu A, Puia VR, Fetti AC, Rusu DR, Berindan-Neagoe I, Al Hajjar N. The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC. Int J Mol Sci 2022; 23:12370. [PMID: 36293225 PMCID: PMC9603983 DOI: 10.3390/ijms232012370] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.
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Affiliation(s)
- Ioana Rusu
- Department of Pathology, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
| | - Radu Pirlog
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Paul Chiroi
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Andreea Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Vlad Radu Puia
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Alin Cornel Fetti
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Daniel Radu Rusu
- Department of Pathology, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Nadim Al Hajjar
- 3rd Department of General Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400186 Cluj-Napoca, Romania
- Department of Surgery, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
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Nagral A, Bangar M, Menezes S, Bhatia S, Butt N, Ghosh J, Manchanayake JH, Mahtab MA, Singh SP. Gender Differences in Nonalcoholic Fatty Liver Disease. Euroasian J Hepatogastroenterol 2022; 12:S19-S25. [PMID: 36466099 PMCID: PMC9681575 DOI: 10.5005/jp-journals-10018-1370] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2023] Open
Abstract
UNLABELLED Nonalcoholic fatty liver disease (NAFLD) has currently emerged as the most common liver disorder in both developed and developing countries. It has been observed that NAFLD exhibits sexual dimorphism, and there is limited understanding on the sex differences in adults with NAFLD. Nonalcoholic fatty liver disease shows marked differences in prevalence and severity with regards to gender. There are considerable biological disparities between males and females attributed to differences in the chromosomal makeup and sex hormone levels, distinct from the gender differences resulting from the sociocultural influences that lead to differences in lifestyle, which have a significant impact on the pathogenesis of this complex disorder. A multitude of factors contributes to the gender disparities seen and need to be researched in-depth to better understand the mechanisms behind them and the therapeutic measures that can be taken. In this article, we will review the gender disparities seen in NAFLD, as well as recent studies highlighting certain gender-specific factors contributing to its varying prevalence and severity. HOW TO CITE THIS ARTICLE Nagral A, Bangar M, Menezes S, et al. Gender Differences in Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S19-S25.
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Affiliation(s)
- Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India; Apollo Hospital, Navi Mumbai, Maharashtra, India
| | - Manisha Bangar
- Division of Gastroenterology and Hepatology, Century Hospitals, Hyderabad, Telangana, India
| | - Sherna Menezes
- Department of Gastroenterology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
| | - Shobna Bhatia
- Department of Gastroenterology, Sir HN Reliance Foundation Hospital, Mumbai, Maharashtra, India
| | - Nazish Butt
- Department of Gastroenterology, Jinnah Postgraduate Medical Center, Karachi, Pakistan
| | - Jhumur Ghosh
- Department of Hepatology, MH Samorita Hospital and Medical College, Dhaka, Bangladesh
| | | | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
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Chen XY, Wang C, Huang YZ, Zhang LL. Nonalcoholic fatty liver disease shows significant sex dimorphism. World J Clin Cases 2022; 10:1457-1472. [PMID: 35211584 PMCID: PMC8855265 DOI: 10.12998/wjcc.v10.i5.1457] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 12/02/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.
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Affiliation(s)
- Xing-Yu Chen
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Cong Wang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Yi-Zhou Huang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
| | - Li-Li Zhang
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 404100, China
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Motamed B, Kohansal Vajargah M, Kalantari S, Shafaghi A. HOMA-IR index in non-diabetic patient, a reliable method for early diagnosis of liver steatosis. CASPIAN JOURNAL OF INTERNAL MEDICINE 2022; 13:519-526. [PMID: 35974947 PMCID: PMC9348208 DOI: 10.22088/cjim.13.3.519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/01/2021] [Accepted: 03/17/2021] [Indexed: 11/22/2022]
Abstract
Background NAFLD is one of the most common liver diseases in the world. HOMA-IR as an indicator of insulin resistance is commonly used in clinical trials in NAFLD patients. The aim of this study was to evaluate the application of HOMA-IR index in the diagnosis of NAFLD. Methods This study was performed on 54 patients with NAFLD and 54 non-NAFLD patients that referred to Razi Hospital in Rasht during 2019-2020. FibroScan was used to diagnose NAFLD in the patient group and ultrasound was used to rule it out in the control group. Metabolic and hepatic parameters were measured for each patient. Data were entered into SPSS 22 software and the necessary analyses were performed. Results The mean age of the subjects in the study was 44.01±13.12 years and ranged from 18 to 75 years. 72.2% of people affected by NAFLD were men (p <0.001) .The optimal cut-off point for HOMA-IR in NAFLD was 1.65 with a sensitivity of 89.7% and a specificity of 76.9% in men and 1.90 with a sensitivity of 86.7% and a specificity of 82.9% in women. Overall, the optimal cut-off point for HOMA-IR in NAFLD was 1.75 with a sensitivity of 87.0% and a specificity of 81.5%. In addition, the results showed that there was no significant relationship between steatosis and hepatic fibrosis with HOMA-IR index. Conclusion The results showed that HOMA-IR can be used as a reliable criterion for early detection of NAFLD.
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Affiliation(s)
- Behrang Motamed
- Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mahsa Kohansal Vajargah
- Department of Internal Medicine, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Saeed Kalantari
- Razi Clinical Research Development Unit, Guilan University of Medical Sciences, Rasht, Iran
| | - Afshin Shafaghi
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
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Akuta N, Kawamura Y, Arase Y, Saitoh S, Fujiyama S, Sezaki H, Hosaka T, Kobayashi M, Kobayashi M, Suzuki Y, Suzuki F, Ikeda K, Kumada H. PNPLA3 genotype and fibrosis-4 index predict cardiovascular diseases of Japanese patients with histopathologically-confirmed NAFLD. BMC Gastroenterol 2021; 21:434. [PMID: 34798835 PMCID: PMC8603578 DOI: 10.1186/s12876-021-02020-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 11/08/2021] [Indexed: 01/01/2023] Open
Abstract
Background Reliable noninvasive predictors of the top three causes of death [cardiovascular diseases (CVDs), malignancies, and liver-related events in patients with non-alcoholic fatty liver disease (NAFLD)] have not yet been determined. Methods We retrospectively investigated the incidence of three complications [CVDs, malignancy (except for liver cancer), and liver-related events] in 477 Japanese patients with histo-pathologically confirmed NAFLD for a median follow-up of 5.9 years. In addition to histological findings, we also investigated noninvasive predictors. Results A score of ≥ 2.67 for the noninvasive diagnosis of stage 4 fibrosis based on the Fibrosis-4 (FIB-4) index indicated a high level area under the receiver operating characteristic (AUROC) curve (0.90), sensitivity (82.9%), specificity (86.4%), and negative predictive value [(NPV) of 98.5%]. The yearly incidence rates of CVDs, malignancies, and liver-related events were found to be 1.04%, 0.83%, and 0.30%, respectively. Multivariate analysis identified a FIB-4 index ≥ 2.67 score as a significant and independent, noninvasive predictor of these three complications. Furthermore, the cumulative incidence rates of CVDs were significantly different among the three genotypes of PNPLA3. PNPLA3 genotype CC, chronic kidney disease (CKD), and FIB-4 index ≥ 2.67 was could be attributed to these three significant CVD risk factors. The rates of CVDs were significantly different among the three subgroups based on the combination of risk factors. In malignancy (except for liver cancer), the incidence rate of colon cancer was 25.0%; in particular, the rate in females was 53.8%. Conclusions Our results highlighted the importance of the PNPLA3 genotype and FIB-4 index ≥ 2.67 on the incidence of complications in Japanese patients with NAFLD, especially the incidence of CVDs. Early diagnosis, based on the presence of one or more risk factors, and early treatment might improve the prognosis for NAFLD patients.
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Affiliation(s)
- Norio Akuta
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
| | - Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Shunichiro Fujiyama
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | | | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
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Akuta N, Kawamura Y, Suzuki F, Saitoh S, Arase Y, Muraishi N, Fujiyama S, Sezaki H, Hosaka T, Kobayashi M, Kobayashi M, Suzuki Y, Ikeda K, Kumada H. Dynamics of Circulating miR-122 Predict Liver Cancer and Mortality in Japanese Patients with Histopathologically Confirmed NAFLD and Severe Fibrosis Stage. Oncology 2021; 100:31-38. [PMID: 34788749 DOI: 10.1159/000519995] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 09/28/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD). METHODS This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years. RESULTS The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios <0.5 (serum miR-122 level at second biopsy to that at first biopsy) than those with ratios ≥0.5. The cumulative survival rates in cases with miR-122 ratios <0.5 tended to be lower than those with ratios ≥0.5. Of the 64 high-risk patients, 39 indicated stage 2 or greater (severe fibrosis stage) at the first liver biopsy and also showed similar results of cumulative liver cancer and survival rates. CONCLUSIONS Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores.
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Affiliation(s)
- Norio Akuta
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Nozomu Muraishi
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Shunichiro Fujiyama
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | | | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
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Lin BZ, Lin TJ, Lin CL, Liao LY, Chang TA, Lu BJ, Chen KY. Differentiation of clinical patterns and survival outcomes of hepatocellular carcinoma on hepatitis B and nonalcoholic fatty liver disease. J Chin Med Assoc 2021; 84:606-613. [PMID: 33871391 DOI: 10.1097/jcma.0000000000000530] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC in recent years. The aim of our study is to investigate and compare the clinical features of HCC in patients with NAFLD and HBV, including age, gender, cirrhosis, liver function tests, largest tumor size, and cancer stage at the time of diagnosis. The survival outcome was compared between the two groups and the significant predictors of mortality were also analyzed in all patients with HCC. METHODS Most patients with HCC were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January 2018 and December 2019. NAFLD was defined as nonviral hepatitis B (negative HBsAg and either positive anti-HBs or negative anti-HBc), nonviral hepatitis C (negative antihepatitis C virus [HCV]), nonalcoholic (alcohol consumption of <30 g/d for men and <20 g/d for women) liver disease, or present or past histological or ultrasonographic evidence of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis. RESULTS NAFLD-related HCC patients were significantly older (median age: 70.0 [61.0-79.0] years vs. 63.0 [56.0-72.0] years, p = 0.012) and heavier (median body mass index [BMI]: 26.6 [24.2-30] kg/m2 vs. 24.8 [22.0-27.1] kg/m2, p = 0.044) than those with HBV-related HCC. They were also more susceptible to diabetes mellitus (DM), and 60.9% (14 of 23) of them had this comorbidity compared with 29.5% (46 of 156) of those with HBV-related HCC (p = 0.003). Only 34.8% (8 of 23) and 71.2% (111 of 156) of patients with NAFLD- and HBV-related HCC were cirrhotic, respectively (p = 0.001). However, gender, tobacco use, international normalized ratio, albumin, creatinine, and cholesterol levels were not significantly different between the two groups. Tumor characteristics such as the Barcelona clinic liver cancer stage, largest tumor size, tumor number, extrahepatic metastasis, and treatment modalities had no significant difference between such groups.According to the Kaplan-Meier method analysis, the overall survival was not significantly different between these two patient groups (log-rank test, p = 0.101). To evaluate which patient group would lead to poor prognosis, we analyzed the survival of all patients through multivariate Cox proportional hazard regression after controlling other factors that may influence the hazard ratio. The analysis revealed that NAFLD and HBV infection as the cause of HCC are not risk factors of poor prognosis. CONCLUSION In conclusion, our study showed NAFLD-related HCC patients were older, heavier, and more had DM than HBV-related. In addition, more NAFLD-related HCC patients were noncirrhotic than HBV-related. The survival rate was similar between NAFLD and HBV-related HCC patients.
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Affiliation(s)
- Bou-Zenn Lin
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC
| | - Tsung-Jung Lin
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC
- University of Taipei, Taipei, Taiwan, ROC
| | - Chih-Lin Lin
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC
| | - Li-Ying Liao
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC
| | - Ting-An Chang
- Department of Pathology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC
| | - Buo-Jia Lu
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan, ROC
| | - Kuan-Yang Chen
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan, ROC
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Mantovani A, Petracca G, Beatrice G, Tilg H, Byrne CD, Targher G. Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals. Gut 2021; 70:962-969. [PMID: 32938692 DOI: 10.1136/gutjnl-2020-322572] [Citation(s) in RCA: 302] [Impact Index Per Article: 75.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 08/05/2020] [Accepted: 08/09/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Follow-up studies have shown that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident diabetes, but currently, it is uncertain whether this risk changes with increasing severity of NAFLD. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes. DESIGN We systematically searched PubMed, Scopus and Web of Science databases from January 2000 to June 2020 using predefined keywords to identify observational studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by imaging techniques or biopsy. Meta-analysis was performed using random-effects modelling. RESULTS 33 studies with 501 022 individuals (30.8% with NAFLD) and 27 953 cases of incident diabetes over a median of 5 years (IQR: 4.0-19 years) were included. Patients with NAFLD had a higher risk of incident diabetes than those without NAFLD (n=26 studies; random-effects HR 2.19, 95% CI 1.93 to 2.48; I2 =91.2%). Patients with more 'severe' NAFLD were also more likely to develop incident diabetes (n=9 studies; random-effects HR 2.69, 95% CI 2.08 to 3.49; I2 =69%). This risk markedly increased across the severity of liver fibrosis (n=5 studies; random-effects HR 3.42, 95% CI 2.29 to 5.11; I2=44.6%). All risks were independent of age, sex, adiposity measures and other common metabolic risk factors. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias. CONCLUSION This updated meta-analysis shows that NAFLD is associated with a ~2.2-fold increased risk of incident diabetes. This risk parallels the underlying severity of NAFLD.
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Affiliation(s)
- Alessandro Mantovani
- Endocrinology and Metabolism, University of Verona Department of Medicine, Verona, Italy
| | - Graziana Petracca
- Endocrinology and Metabolism, University of Verona Department of Medicine, Verona, Italy
| | - Giorgia Beatrice
- Endocrinology and Metabolism, University of Verona Department of Medicine, Verona, Italy
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, University of Innsbruck, Innsbruck, Austria
| | | | - Giovanni Targher
- Endocrinology and Metabolism, University of Verona Department of Medicine, Verona, Italy
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Wei L, Cheng X, Luo Y, Yang R, Lei Z, Jiang H, Chen L. Lean non-alcoholic fatty liver disease and risk of incident diabetes in a euglycaemic population undergoing health check-ups: A cohort study. DIABETES & METABOLISM 2021; 47:101200. [DOI: 10.1016/j.diabet.2020.08.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/11/2020] [Accepted: 08/17/2020] [Indexed: 12/15/2022]
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Abstract
PURPOSE OF REVIEW Aging-related comorbidities, including liver disease, represent the main drivers of morbidity and mortality in people with HIV (PWH). Nonalcoholic fatty liver disease (NAFLD) seems a frequent comorbidity in aging PWH nowadays. NAFLD results from a fat deposition into the liver parenchyma that may evolve to nonalcoholic steatohepatitis (NASH), a state of hepatocellular inflammation and injury in response to the accumulated fat leading to liver fibrosis and cirrhosis. We here review the current status of knowledge regarding this emerging comorbidity in PWH. RECENT FINDINGS Recent studies suggest that PWH are at higher risk for both NASH and NASH-related liver fibrosis. Several hypothesized pathogenic mechanisms may account for this finding, including increased metabolic comorbidities, hepatotoxic effect of lifelong antiretroviral therapy, and chronic HIV infection. In clinical practice, non-invasive diagnostic tests, such as serum biomarkers and elastography, may help identify patients with NASH-related fibrosis, thus improving risk stratification, and enhancing clinical management decisions, including early initiation of interventions such as lifestyle changes and potential pharmacologic interventions. Clinicians should remain informed of the frequency, significance, and diagnostic and management approach to NASH in PWH.
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Affiliation(s)
- Adriana Cervo
- Division of Infectious Diseases, Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
- Department of Health Promotion Sciences and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Palermo, Italy
| | - Mohamed Shengir
- Division of Experimental Medicine, McGill University, Montreal, Canada
| | - Keyur Patel
- Division of Gastroenterology, University Health Network Toronto, Toronto General Hospital, Toronto, Canada
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, Chronic Viral Illness Service Royal Victoria Hospital, McGill University Health Centre, 1001 Blvd. Décarie, Montreal, QC H4A 3J1, Canada.
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Risk of cardiovascular disease in patients with fatty liver disease as defined from the metabolic dysfunction associated fatty liver disease or nonalcoholic fatty liver disease point of view: a retrospective nationwide claims database study in Japan. J Gastroenterol 2021; 56:1022-1032. [PMID: 34601620 PMCID: PMC8531127 DOI: 10.1007/s00535-021-01828-6] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 09/15/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have important associations with cardiovascular disease (CVD). The main objective of this study was to compare the frequency of incidence rate of CVD in the NAFLD or MAFLD patients utilizing a large claims database. METHODS Using the JMDC database from April 2013 to March 2019, we retrospectively analyzed data for 1,542,688 and 2,452,949 people to estimate the relationship between CVD and NAFLD, MAFLD, respectively. RESULTS The incidence rates of CVD were 0.97 (95% CI 0.94-1.01) and 2.82 (95% CI 2.64-3.01) per 1000 person-years in the non-NAFLD and NAFLD groups, respectively, and 1.01 (95% CI 0.98-1.03) and 2.69 (95% CI 2.55-2.83) per 1000 person-years in the non-MAFLD and MAFLD groups, respectively. The overall prevalence of hypertriglyceridemia and diabetes mellitus (DM) was 13.1, and 4.2%, respectively, in the non-NAFLD group and 63.6, and 20.2%, respectively, in the NAFLD group. The overall prevalenceof hypertriglyceridemia and DM was 13.6 and 4.3%, respectively, in the non-MAFLD group and 64.1, and 20.6%, respectively, in the MAFLD group. HRs for CVD increased with hypertriglyceridemia and DM. CONCLUSIONS Results indicated that incident rate of CVD increased with NAFLD/MAFLD; the complication rate of DM and hypertriglyceridemia among NAFLD/MAFLD patients is high and may affect the development of CVD.
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Batisti J, Mehal WZ. Nonalcoholic Fatty Liver Disease in the Post Liver Transplant Patient. CURRENT TRANSPLANTATION REPORTS 2020. [DOI: 10.1007/s40472-020-00303-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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21
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Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis - epidemiology, risk factors, clinical implications and treatment. Clin Exp Hepatol 2020; 6:170-175. [PMID: 33145423 PMCID: PMC7592090 DOI: 10.5114/ceh.2020.99506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Accepted: 06/02/2020] [Indexed: 12/17/2022] Open
Abstract
In recent years, rapid growth of incidence of metabolic syndrome, obesity and diabetes has been noted worldwide. Concurrent non-alcoholic steatohepatitis (NASH) has become a dominant factor of hepatic cirrhosis and hepatocellular carcinoma (HCC). The most important risk factors of transition from NASH to HCC are the degree of liver fibrosis, diabetes, obesity, age and male gender. Body mass index (BMI) reduction and increase of physical activity limit the risk of occurrence of HCC. Also, treatment of diabetes with metformin and application of statins have potential anticancer effects. Patients with HCC due to NASH should be treated in line with BCLC staging. Distant results of HCC therapy in the course of non-alcoholic fatty liver disease (NAFLD) are similar to the results of cancer of different aetiologies. However, patients with the metabolic syndrome are at high perioperative risk, and thus require accurate preparation, especially cardiological, in order to avoid that risk.
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22
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Akuta N, Kawamura Y, Fujiyama S, Sezaki H, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Arase Y, Ikeda K, Kumada H. SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology. Intern Med 2020; 59:1931-1937. [PMID: 32448832 PMCID: PMC7492114 DOI: 10.2169/internalmedicine.4398-19] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Objective The aim of this study was to determine the long-term effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology. Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated. Patients Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin, an SGLT2i, and liver biopsies were obtained at the 3 points of pretreatment, 24 weeks, and ≥1 year (third liver biopsy) after the start of treatment. Six of seven patients were evaluated with third liver biopsy at the point of three or more years. The primary outcome was liver histopathological changes (defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage, compared to pretreatment). Results All 7 patients showed worsening of body mass index and waist circumference at the third liver biopsy compared to 24 weeks. However, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage improved at the third liver biopsy in 57%, 43%, 14%, and 29% of the patients, respectively, compared to pretreatment. One of the seven patients showed histopathological worsening at the third liver biopsy compared to pretreatment, but the improvement was maintained in the other six patients. Conclusion The long-term treatment of NAFLD complicated by T2DM using an SGLT2i is associated with long-term improvement in liver histopathology despite the worsening of clinical features.
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Affiliation(s)
- Norio Akuta
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Shunichiro Fujiyama
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | | | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Japan
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23
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de Campos PB, Oliveira CP, Stefano JT, Martins-Filho SN, Chagas AL, Herman P, D'Albuquerque LC, Alvares-da-Silva MR, Longatto-Filho A, Carrilho FJ, Alves VAF. Hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) - pathological evidence for a predominance of steatohepatitic inflammatory non-proliferative subtype. Histol Histopathol 2020; 35:729-740. [PMID: 31858523 DOI: 10.14670/hh-18-194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES This study evaluated clinical and pathological aspects of patients with hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) and related these factors to immunohistochemical markers representative of the proliferative class. METHODS We evaluated 35 HCC nodules from 21 patients diagnosed with NAFLD undergoing liver resection (n=12) or liver transplantation (n=8) or both (n=1). Demographic, clinical and biochemical data were compared to histological features and to immunohistochemical reactivity for K19 and Ki-67. RESULTS Cirrhosis was present in 58% of patients. Ages ranged from 50 to 77 years. Sixteen patients (76%) were male and had type 2 diabetes mellitus, 81% had arterial hypertension, and 90% had BMI above 25 kg/m². Alpha-fetoprotein levels were normal in 62% of patients. Twenty-five (70%) nodules were diagnosed as "steatohepatitic HCC". Only 32% of the nodules presented high levels of Ki-67 (>10%) and/or K19 (>5%), although 63% were poorly differentiated (G.3/G.4) according to Edmondson & Steiner grading system. K19 positivity (>5%) was associated with higher degree of intratumoral inflammation (G.2/G.3), and with fibrosis, both at the center of the tumor and at the tumor front, whereas Ki-67 positivity (>10%) was associated with ballooning of neoplastic cells and occurred in more than 70% in non-cirrhotic patients. CONCLUSION NAFLD-related HCC was found in non-cirrhotic patients in 42% of cases, alpha-fetoprotein level was normal in 63% and "steatohepatitic HCC" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially "an inflammatory, non-proliferative subtype of HCC".
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Affiliation(s)
| | - Claudia P Oliveira
- University of São Paulo Medical School, São Paulo, SP, Brasil.
- Laboratory of Clinical and Experimental Gastroenterology (LIM-07) Department of Gastroenterology and Hepatology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - José T Stefano
- Laboratory of Clinical and Experimental Gastroenterology (LIM-07) Department of Gastroenterology and Hepatology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - Sebastião N Martins-Filho
- Department of Pathology (LIM-14), Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - Aline L Chagas
- Department of Gastroenterology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - Paulo Herman
- Department of Gastroenterology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - Luiz C D'Albuquerque
- Department of Gastroenterology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - Mário R Alvares-da-Silva
- Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brasil
| | - Adhemar Longatto-Filho
- Department of Pathology (LIM-14), Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Flair J Carrilho
- University of São Paulo Medical School, São Paulo, SP, Brasil
- Laboratory of Clinical and Experimental Gastroenterology (LIM-07) Department of Gastroenterology and Hepatology, Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
| | - Venancio A F Alves
- University of São Paulo Medical School, São Paulo, SP, Brasil
- Department of Pathology (LIM-14), Hospital das Clínicas HCFMUSP, School of Medicine, University of São Paulo, São Paulo, SP, Brasil
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24
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Araki N, Takahashi H, Takamori A, Kitajima Y, Hyogo H, Sumida Y, Tanaka S, Anzai K, Aishima S, Chayama K, Fujimoto K, Eguchi Y. Decrease in fasting insulin secretory function correlates with significant liver fibrosis in Japanese non-alcoholic fatty liver disease patients. JGH OPEN 2020; 4:929-936. [PMID: 33102766 PMCID: PMC7578285 DOI: 10.1002/jgh3.12367] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 05/14/2020] [Indexed: 12/28/2022]
Abstract
Background and Aim Non‐alcoholic fatty liver disease (NAFLD) is typically associated with metabolic syndrome and diabetes, and insulin resistance is involved in its pathogenesis. However, the relationship between insulin secretion and NAFLD is unclear. We aimed to characterize the relationship between fasting insulin secretory function (ISF), evaluated using the homeostatic model assessment‐beta cell function (HOMA‐β) and the severity of fibrosis during NAFLD. Methods A‐β was calculated in 188 patients with biopsy‐confirmed NAFLD, and the correlations between Log HOMA‐β and clinical parameters, including hepatic fibrosis, were calculated. Results Log HOMA‐β was significantly lower in NAFLD patients with significant fibrosis (stages 2–4) than in those in the early stages (stages 0–1) (median [interquartile range]) (2.1 [1.9–2.4] vs 2.0 [1.8–2.2], P = 0.04). The prevalence of significant fibrosis decreased with increasing Log HOMA‐β: it was 59.2% in participants with low ISF (Log HOMA‐β < 1.85), 43.6% in those with intermediate ISF (1.85 ≤ Log HOMA‐β < 2.25), and 68.0% in those with high ISF (Log HOMA‐β ≥ 2.25). Patients with lower Log HOMA‐β had lower current body mass index (BMI), BMI at 20 years of age, and peak lifetime BMI than patients with intermediate or high Log HOMA‐β. Conclusions Fasting ISF decreased alongside the development of liver fibrosis in NAFLD, suggesting that an impaired β cell function has a characteristic finding of significant liver fibrosis in relatively nonobese Japanese patients.
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Affiliation(s)
- Norimasa Araki
- Department of Internal Medicine, Faculty of Medicine Saga University Saga Japan
| | - Hirokazu Takahashi
- Department of Internal Medicine, Faculty of Medicine Saga University Saga Japan
| | - Ayako Takamori
- Clinical Research Center Saga University Hospital Saga Japan
| | - Yoichiro Kitajima
- Department of Internal Medicine, Faculty of Medicine Saga University Saga Japan.,Liver Center Saga University Hospital Saga Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology and Hepatology JA Hiroshima General Hospital Hatsukaichi Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine Aichi Medical University Aichi Japan
| | - Saiyu Tanaka
- Center for Digestive and Liver Disease Nara City Hospital Nara Japan
| | - Keizo Anzai
- Department of Internal Medicine, Faculty of Medicine Saga University Saga Japan
| | - Shinichi Aishima
- Department of Pathology & Microbiology, Faculty of Medicine Saga University Saga Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism Graduate School of Biomedical and Health Sciences, Hiroshima University Hiroshima Japan
| | - Kazuma Fujimoto
- Faculty of Medicine International University of Health and Welfare Fukuoka Japan
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25
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Johnston MP, Patel J, Byrne CD. Diabetes is associated with increased risk of hepatocellular carcinoma in non-alcoholic steatohepatitis with cirrhosis-implications for surveillance and future pharmacotherapy. Hepatobiliary Surg Nutr 2020; 9:230-234. [PMID: 32355688 DOI: 10.21037/hbsn.2019.10.09] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Michael P Johnston
- Department of Hepatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Janisha Patel
- Department of Hepatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Christopher D Byrne
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.,National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
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26
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Lonardo A, Suzuki A. Sexual Dimorphism of NAFLD in Adults. Focus on Clinical Aspects and Implications for Practice and Translational Research. J Clin Med 2020; 9:1278. [PMID: 32354182 PMCID: PMC7288212 DOI: 10.3390/jcm9051278] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 04/23/2020] [Accepted: 04/24/2020] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) embraces the clinico-pathological consequences of hepatic lipotoxicity and is a major public health problem globally. Sexual dimorphism is a definite feature of most human diseases but, under this aspect, NAFLD lags behind other medical fields. Here, we aim at summarizing and critically discussing the most prominent sex differences and gaps in NAFLD in humans, with emphasis on those aspects which are relevant for clinical practice and translational research. Sexual dimorphism of NAFLD is covered with references to the following areas: disease prevalence and risk factors, pathophysiology, comorbidities, natural course and complications. Finally, we also discuss selected gender differences and whether sex-specific lifestyle changes should be adopted to contrast NAFLD in men and women.
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Affiliation(s)
- Amedeo Lonardo
- Operating Unit Metabolic Syndrome, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, 41126 Baggiovara MO, Italy
| | - Ayako Suzuki
- Division of Gastroenterology, Durham VA Medical Center and Duke University Medical Center, Durham, NC 27705, USA;
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27
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Lu WP, Tang HW, Yang ZY, Jiang K, Chen YL, Lu SC. A proposed modification for the Barcelona Clinic Liver Cancer staging system: Adding bile duct tumor thrombus status in patients with hepatocellular carcinoma. Am J Surg 2020; 220:965-971. [PMID: 32336518 DOI: 10.1016/j.amjsurg.2020.04.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 03/18/2020] [Accepted: 04/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The Barcelona Clinic Liver Cancer (BCLC) staging system is widely applied to stage hepatocellular carcinoma (HCC). However, it may be inaccurate when applied to East Asian HCC patients. In this study, a large Chinese HCC cohort was analyzed to evaluate possible modifications for the BCLC staging system. METHODS Between January 1995 and December 2009, 622 HCC patients who underwent hepatectomy were enrolled. Prognostic risk factors were analyzed using univariate and multivariate analyses. The ability of the modified system to predict survival was evaluated by determining the area under the receiver operating characteristic curve. RESULTS Patients without bile duct tumor thrombus (BDTT; 1-, 3- and 5-year overall survival, 80%, 60% and 48%, respectively) showed a substantial survival advantage over those with BDTT (1-, 3- and 5-year overall survival, 77%, 42% and 23%, respectively; χ2 = 6.280, P = 0.012). In BCLC stage 0-A patients, significant differences were identified between the BDTT group and the non-BDTT group, while no such differences were found in BCLC stage B patients. Based on this finding, BCLC stage 0-A BDTT patients were recategorized into stage B. The modified BCLC classification featured better performance in the prediction of overall survival than the original system (modified BCLC χ2 = 53.596, P < 0.001; original BCLC χ2 = 46.335, P < 0.001). The ability to predict mortality was also slightly higher using the modified BCLC system. CONCLUSIONS Modification of the BCLC system to include BDTT status might further enhance its prognostic ability.
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Affiliation(s)
- Wen-Ping Lu
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China.
| | - Hao-Wen Tang
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China.
| | - Zhan-Yu Yang
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Kai Jiang
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yong-Liang Chen
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shi-Chun Lu
- Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
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28
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Berkan-Kawińska A, Piekarska A. Hepatocellular carcinoma in non-alcohol fatty liver disease - changing trends and specific challenges. Curr Med Res Opin 2020; 36:235-243. [PMID: 31631714 DOI: 10.1080/03007995.2019.1683817] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background and Aims: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. The etiology of this disease is known in 90% of the patients, and it is viral in most of the cases. According to recent predictions, nearly half of the world population will be suffering from obesity by 2030. Consequently, non-alcoholic fatty liver disease (NAFLD) may play a growing role in HCC epidemiology. In this review, we sought to explore the relationship between liver steatosis and HCC.Methods: A narrative review was conducted using the PubMed MeSH search. The eligible papers were identified using a standard PubMed search with relevant key terms and various synonyms.Results: According to the results, patients with NAFLD-HCC tended to be older than those with hepatitis C virus (HCV)-HCC, and they were more often obese and had concomitant diseases, such as diabetes. On the other hand, the synthetic liver function was better preserved in NAFLD-HCC patients, who also obtained lower scores on the Model for End-stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP). However, it has to be noted that HCC in patients with non-alcoholic steatohepatitis (NASH) may develop without underlying cirrhosis. Although NASH-HCC is usually smaller and well-differentiated compared to HCV-HCC, the prognosis is similar in both groups. Efficient HCC screening in NASH cirrhosis poses a challenge because it is difficult to perform ultrasound examination in obese patients and alfa-fetoprotein level is no longer considered reliable.Conclusions: The constantly increasing prevalence of NAFLD in the general population can contribute to a growing role of NAFLD/NASH in HCC epidemiology. Moreover, some particular challenges specific for patients with liver steatosis may impede proper HCC diagnosis, treatment and follow-up.
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Affiliation(s)
| | - Anna Piekarska
- Infectious Diseases and Hepatology Department, Medical University of Lodz, Lodz, Poland
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29
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Akuta N, Kawamura Y, Arase Y, Saitoh S, Fujiyama S, Sezaki H, Hosaka T, Kobayashi M, Kobayashi M, Suzuki Y, Suzuki F, Ikeda K, Kumada H. Circulating MicroRNA-122 and Fibrosis Stage Predict Mortality of Japanese Patients With Histopathologically Confirmed NAFLD. Hepatol Commun 2019; 4:66-76. [PMID: 31909356 PMCID: PMC6939501 DOI: 10.1002/hep4.1445] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/11/2019] [Indexed: 12/16/2022] Open
Abstract
The impact of circulating microRNA‐122 (miR‐122) on mortality in patients with histopathologically confirmed nonalcoholic fatty liver disease (NAFLD) remains unclear. We analyzed the overall survival rates in 441 Japanese patients with histopathologically confirmed NAFLD after a median follow‐up period of 4.7 years. We also determined the clinicopathologic, genetic, and epigenetic parameters, including serum miR‐122 levels, for prediction of mortality. Of the 441 study patients, 21 (4.8%) died during the follow‐up period. The cumulative survival rates were 95.4% and 90.6% at the end of 5 and 10 years, respectively. Multivariate analysis identified history of liver cancer (presence; hazard ratio [HR], 4.94; 95% confidence interval [CI], 1.84‐13.3), serum miR‐122 (<1.00 fold change; HR, 4.35; 95% CI, 0.06‐0.83), and fibrosis‐4 index (FIB‐4 index) (≥1.30; HR, 15.7; 95% CI, 2.01‐122) as significant risk factors of mortality. Cumulative survival rates varied significantly among patients with none/one risk factor, two risk factors, and three risk factors; particularly, the survival rate of patients with three risk factors was significantly lower than those with two risk factors and none/one risk factor. Two or more risk factors were identified in 17 of 21 (81.0%) death cases. Conclusion: The importance of serum miR‐122 and FIB‐4 index as risk factors for mortality in Japanese patients with histopathologically confirmed NAFLD is shown. Early diagnosis based on the presence of more than one risk factor and early treatment might improve the prognosis.
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Affiliation(s)
- Norio Akuta
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Yusuke Kawamura
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Yasuji Arase
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Satoshi Saitoh
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Shunichiro Fujiyama
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Hitomi Sezaki
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Tetsuya Hosaka
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Masahiro Kobayashi
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | | | - Yoshiyuki Suzuki
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Fumitaka Suzuki
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Kenji Ikeda
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
| | - Hiromitsu Kumada
- Department of Hepatology Toranomon Hospital and Okinaka Memorial Institute for Medical Research Tokyo Japan
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