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Barb D, Kalavalapalli S, Godinez Leiva E, Bril F, Huot-Marchand P, Dzen L, Rosenberg JT, Junien JL, Broqua P, Rocha AO, Lomonaco R, Abitbol JL, Cooreman MP, Cusi K. Pan-PPAR agonist lanifibranor improves insulin resistance and hepatic steatosis in patients with T2D and MASLD. J Hepatol 2025; 82:979-991. [PMID: 39824443 DOI: 10.1016/j.jhep.2024.12.045] [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: 06/24/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/20/2025]
Abstract
BACKGROUND & AIMS Lanifibranor is a pan-PPAR agonist that improves glucose/lipid metabolism and reverses steatohepatitis and fibrosis in adults with metabolic dysfunction-associated steatohepatitis (MASH). We tested its effect on insulin resistance (IR) at the level of different target tissues in relation to changes in intrahepatic triglyceride (IHTG) content. METHODS In this single-center phase II study, 38 patients with type 2 diabetes and MASLD were randomized 1:1 to receive lanifibranor 800 mg or placebo for 24 weeks. The primary endpoint was the change in IHTG (1H-MRS). The main prespecified secondary endpoint was the change in hepatic, muscle and adipose tissue insulin sensitivity using the gold-standard euglycemic hyperinsulinemic clamp technique to measure glucose turnover. Other secondary endpoints included changes in cardiometabolic parameters (i.e., HbA1c, lipid profile, adiponectin). RESULTS Lanifibranor significantly lowered IHTG compared to placebo (full analysis set [FAS] -44% vs. -12%, respectively; least squares mean difference -31%, 95% CI -51 to -12%; in completers -50% vs. -16%; both p <0.01). More patients in the lanifibranor group (vs. the placebo group) achieved a ≥30% IHTG reduction (FAS 65% vs. 22%; completers 79% vs. 29%; both p <0.01) and steatosis resolution (FAS 25% vs. 0%; p <0.05). Lanifibranor significantly improved hepatic and peripheral IR (i.e. fasting endogenous [primarily hepatic] glucose production, hepatic IR, and insulin-stimulated muscle glucose disposal or Rd). Secondary metabolic endpoints also improved (fasting glucose, insulin, HOMA-IR, HbA1c, HDL-C), and adiponectin increased 2.4-fold (all p <0.001). Lanifibranor caused modest weight gain (+2.7%). Adverse events were mild (gastrointestinal side effects, hemoglobin decrease) and drug-related treatment-emergent adverse events leading to study discontinuation were balanced between groups. CONCLUSIONS Lanifibranor significantly improves hepatic, muscle and adipose tissue IR. Lanifibranor treatment was safe and effective in reducing hepatic steatosis and cardiometabolic risk factors associated with metabolic dysfunction. IMPACT AND IMPLICATIONS No prior studies have evaluated the effect of lanifibranor on insulin sensitivity at the level of muscle, liver and adipose tissue and its relationship to changes in intrahepatic triglyceride (IHTG) content in insulin-resistant individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. We observed a significant decrease in IHTG after 24 weeks of treatment (by ∼50%, p <0.001 vs. placebo) that was associated with a major improvement in hepatic and peripheral (Rd) insulin sensitivity, restoration of adipose tissue function and improvement in cardiometabolic risk factors. This study has important clinical implications because it offers proof-of-concept that targeting the key underlying metabolic defects in MASLD (i.e. insulin resistance, lipotoxicity and hyperglycemia) can restore cardiometabolic health. It offers a compelling rationale for lanifibranor treatment in individuals with MASLD, either alone or in combination with weight loss and other treatment strategies. CLINICALTRIALS GOV IDENTIFIER NCT03459079.
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Affiliation(s)
- Diana Barb
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | - Srilaxmi Kalavalapalli
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | - Eddison Godinez Leiva
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | - Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Lucile Dzen
- Inventiva Pharma, Daix, France, and New York, NY, USA
| | - Jens T Rosenberg
- Advanced Magnetic Resonance Imaging and Spectroscopy Facility, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
| | | | - Pierre Broqua
- Inventiva Pharma, Daix, France, and New York, NY, USA
| | - Andrea Ortiz Rocha
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | | | | | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA.
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Chen HF, Chang YY, Chen P, Shen XH, Chang CH, Hsu WL. Risks of liver cirrhosis, hepatocellular carcinoma, hepatic-related complications, and mortality in patients with type 2 diabetes in Taiwan. World J Diabetes 2025; 16:104576. [DOI: 10.4239/wjd.v16.i5.104576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/25/2025] [Accepted: 03/21/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Hepatitis B and C and alcoholic liver disease are the principal causes of hepatic-related morbidity and mortality. However, evidence of the associations between diabetes without the above risk factors and hepatic-related study endpoints is not well understood. In addition, the effects of associated metabolic dysfunction and exercise on hepatic outcomes are still not clear.
AIM To investigate the incidence and relative hazards of cirrhosis of the liver, hepatocellular carcinoma (HCC), hepatic-related complications and mortality in patients with type 2 diabetes (T2D) who were nonalcoholic and serologically negative for hepatitis B and C in Taiwan.
METHODS A total of 33184 T2D patients and 648746 nondiabetic subjects selected from Taiwan’s adult preventive health care service were linked to various National Health Insurance databases, cancer registry, and death registry to identify cirrhosis of the liver, HCC, hepatic-related complications, and mortality. The Poisson assumption and Cox proportional hazard regression model were used to estimate the incidences and relative hazards of all hepatic-related study endpoints, respectively. We also compared the risk of hepatic outcomes stratified by age, sex, associated metabolic dysfunctions, and regular exercise between T2D patients and nondiabetic subjects.
RESULTS Compared with nondiabetic subjects, T2D patients had a significantly greater incidence (6.32 vs 17.20 per 10000 person-years) and greater risk of cirrhosis of the liver [adjusted hazard ratio (aHR) 1.45; 95%CI: 1.30-1.62]. The aHRs for HCC, hepatic complications, and mortality were 1.81, 1.87, and 2.08, respectively. An older age, male sex, obesity, hypertension, and dyslipidemia further increased the risks of all hepatic-related study endpoints, and regular exercise decreased the risk, irrespective of diabetes status.
CONCLUSION Patients with T2D are at increased risk of cirrhosis of the liver, HCC, hepatic-related complications, and mortality, and associated metabolic dysfunctions provide additional hazard. Coordinated interprofessional care for high-risk T2D patients and diabetes education, with an emphasis on the importance of physical activity, are crucial for minimizing hepatic outcomes.
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Affiliation(s)
- Hua-Fen Chen
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
- Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
| | - Yung-Yueh Chang
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City 100, Taiwan
| | - Peter Chen
- Department of Gastroenterology, Choninn Hospital, Choninn Medical Group, New Taipei City 220, Taiwan
| | - Xiao-Han Shen
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
- Master Program of Big Data in Medical Healthcare Industry, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
- Data Science Center, Fu Jen Catholic University, New Taipei City 242, Taiwan
| | - Chin-Huan Chang
- Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan
| | - Wan-Lun Hsu
- Master Program of Big Data in Medical Healthcare Industry, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan
- Data Science Center, Fu Jen Catholic University, New Taipei City 242, Taiwan
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Yi H, Zhang Y, Zhou Z, Sun W, Wang Y, Tao W, Yu H, Yao L, Li J, Li L. Diagnostic performance of noninvasive tests for identifying advanced fibrosis in metabolic dysfunction-associated fatty liver disease with mixed etiologies. Endocr Pract 2025:S1530-891X(25)00140-5. [PMID: 40334939 DOI: 10.1016/j.eprac.2025.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 04/10/2025] [Accepted: 04/28/2025] [Indexed: 05/09/2025]
Abstract
OBJECTIVES To assess the performance of fibrosis-4 index (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS) and aspartate aminotransferase to platelet ratio index (APRI) for advanced fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) subgroups categorized by concomitant liver conditions. METHODS We conducted a multicentered study comprising inpatients with type 2 diabetes mellitus (T2DM) and MAFLD. Participants were categorized into two groups: MAFLD with pure metabolic etiologies (MAFLD-P) and MAFLD with mixed etiologies (MAFLD-M). Diagnostic performance of FIB-4, NFS and APRI was assessed by area under receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS This study comprised a total of 1475 participants, with a mean (SD) age of 58.4 (13) years and 835 (56.6%) males. FIB-4 and APRI had higher AUCs for advanced fibrosis in the MAFLD-M group than in the MAFLD-P group (MAFLD-M vs MAFLD-P: FIB-4 0.680 vs 0.591, p = 0.0442; APRI 0.723 vs 0.631, p = 0.0363). No significant difference was observed in the AUC of NFS between the two subgroups (MAFLD-M 0.572 vs MAFLD-P 0.617; p = 0.3237). Besides, the sensitivity of FIB-4 (69.6% vs 54.0%; p = 0.019) and APRI (43.5% vs 26.1%; p = 0.005) was higher in the MAFLD-M group. However, no significant difference in sensitivity of NFS and specificity of FIB-4, NFS and APRI was observed between subgroups. CONCLUSIONS In this diagnostic study of the T2DM population, FIB-4 and APRI showed better performance for identifying advanced fibrosis in MAFLD with mixed etiologies.
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Affiliation(s)
- He Yi
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China
| | - Yan Zhang
- Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212000, China
| | - Ziwei Zhou
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China
| | - Weixia Sun
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China
| | - Yifan Wang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China
| | - Wenxuan Tao
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China
| | - Hekai Yu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China
| | - Liqin Yao
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, 214200, China.
| | - Jia Li
- Department of Ultrasound, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China; Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Southeast University, Nanjing, 210009, China.
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Younossi ZM, Razavi H, Sherman M, Allen AM, Anstee QM, Cusi K, Friedman SL, Lawitz E, Lazarus JV, Schuppan D, Romero-Gómez M, Schattenberg JM, Vos MB, Wong VWS, Ratziu V, Hompesch M, Sanyal AJ, Loomba R. Addressing the High and Rising Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH): From the Growing Prevalence to Payors' Perspective. Aliment Pharmacol Ther 2025; 61:1467-1478. [PMID: 39967239 DOI: 10.1111/apt.70020] [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: 10/31/2024] [Revised: 12/10/2024] [Accepted: 01/29/2025] [Indexed: 02/20/2025]
Abstract
BACKGROUND The continuum of metabolic syndrome encompasses a spectrum of dysfunctions impacting obesity-linked insulin resistance, glucose homeostasis, lipid metabolism and pro-inflammatory immune responses. The global prevalence of metabolic diseases, including diabetes, chronic liver disease, cardiometabolic disease and kidney disease, has surged in recent decades, contributing significantly to population mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a leading cause of liver disease worldwide. MASLD poses a significant global health challenge with its rising prevalence, placing a substantial burden on healthcare systems, impacts patient well-being and incurs significant economic costs. Addressing MASLD requires a comprehensive understanding of its interconnected factors, including its prevalence, healthcare burden and economic implications. Lack of awareness, imprecise non-invasive diagnostic methods and ineffective preventive interventions are core components of the MASLD-related problem. AIM The aim of this article was to summarise the global burden of MASLD from the payer's perspective. METHODS We carried out a review of the global comprehensive burden of MASLD. These topics led to discussions and insights by an expert panel during the 7th Metabolic Continuum Roundtable meeting, which took place in November 2023. This meeting focused on the burden, patient-reported outcomes and health economics, from payor and societal perspectives, and aimed to identify opportunities for improving patient care, optimise resource allocation and mitigate the overall impact on individuals and society related to MASLD. During the roundtable, an emphasis emerged on the need for greater awareness and strategic deployment of diagnostic, therapeutic and preventative measures to address MASLD effectively. CONCLUSION The global burden of MASLD is high and growing. Prioritising the prevention of metabolic dysregulation and timely therapeutic interventions can yield a holistic strategy to combat MASLD, its progression and potentially lower disease costs. TRIAL REGISTRATION NCT06309992.
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Affiliation(s)
- Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia, USA
- The Global NASH Council, Washington, DC, USA
| | - Homie Razavi
- Center for Disease Analysis Foundation, Lafayette, Colorado, USA
| | - Michael Sherman
- RA Capital Management, L.P., Boston, Massachusetts, USA
- Department of Population Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Alina M Allen
- Division of Gastroenterology and Hepatology, Mayo Clinic Minnesota, Rochester, Minnesota, USA
| | - Quentin M Anstee
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
- Newcastle NIHR Biomedical Research Center, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes & Metabolism, University of Florida, Gainesville, Florida, USA
| | - Scott L Friedman
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Eric Lawitz
- Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Texas, USA
| | - Jeffrey V Lazarus
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
- City University of New York Graduate School of Public Health and Health Policy (CUNY SPH), New York, New York, USA
| | - Detlef Schuppan
- Mainz University, Mainz, Germany
- Germany & Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Manuel Romero-Gómez
- Department of Medicine, UCM Digestive Diseases, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), CIBEREHD, ISCIII, University of Seville, Seville, Spain
| | - Jörn M Schattenberg
- Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Miriam B Vos
- Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Vincent Wai-Sun Wong
- State Key Laboratory of Digestive Disease, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Vlad Ratziu
- Sorbonne Université and Pitié-Salpêtrière Hospital Paris, Paris, France
| | | | - Arun J Sanyal
- Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Rohit Loomba
- Division of Gastroenterology and Hepatology at UC San Diego, MASLD Research Center California, La Jolla, California, USA
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Cui Y, Qu Z, Li L, Hu W. Gender difference in the association between serum uric acid and metabolic dysfunction-associated steatotic liver disease in patients with newly diagnosed type 2 diabetes. BMC Gastroenterol 2025; 25:322. [PMID: 40307757 PMCID: PMC12042553 DOI: 10.1186/s12876-025-03917-9] [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: 01/10/2025] [Accepted: 04/18/2025] [Indexed: 05/02/2025] Open
Abstract
PURPOSE To investigate the relationship between serum uric acid (SUA) levels and metabolic dysfunction-associated steatotic liver disease (MASLD) in newly diagnosed type 2 diabetic patients. METHODS We performed this retrospective research among 1087 inpatients with new-onset type 2 diabetes millitus (T2DM). Data were analyzed according to gender. Then, the populations were stratified according to their body mass index (BMI) levels in men and women, respectively. The physical and biochemical indicators were measured and recorded. The relationship between SUA and MASLD was estimated using logistic regression analysis, and the unadjusted and adjusted odds ratios (ORs) were calculated. RESULTS After adjusting for age, BMI, and other components of the metabolic syndrome, SUA was independently associated with MASLD only in men, but not in women. In addition, for men, the SUA levels were independently associated with MASLD in both non-overweight/obesity and overweight/obesity group. However, for women, the SUA levels were independently related to MASLD in non-overweight/obesity group. There was no association between SUA and MASLD in women with overweight/obesity. CONCLUSION In newly diagnosed type 2 diabetic patients, elevated SUA is an independent predictor for the risk of MASLD in males. In females, the relationship between SUA and MASLD may depend on BMI, with significance only in non-overweight/obese individuals.
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Affiliation(s)
- Yuliang Cui
- Department of Endocrinology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, 253000, China
| | - Zhenzhen Qu
- Department of Endocrinology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, 253000, China
| | - Lingling Li
- Department of Health Management, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, 253000, China
| | - Wenmei Hu
- Department of Endocrinology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, 253000, China.
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Li M, Yu B, Zhang X, Pan J, Tang L, Zhang Y, Wang R, Zeng H, Yang S. Association between alcohol consumption and hepatic fibrosis in Chinese adult males with metabolic dysfunction-associated steatotic liver disease. Front Med (Lausanne) 2025; 12:1572853. [PMID: 40357286 PMCID: PMC12066787 DOI: 10.3389/fmed.2025.1572853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 04/10/2025] [Indexed: 05/15/2025] Open
Abstract
Background The impact of moderate drinking on the risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) remains controversial worldwide. Notably, China, with the fastest-growing incidence of NAFLD and the highest number of alcohol-attributable deaths globally, has relatively few studies addressing this issue. This study aimed to explore the association between alcohol consumption and liver fibrosis in Chinese men with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We recruited 4,683 male employees diagnosed with MASLD from southwest China, including 4,287 with pure MASLD and 396 with metabolic and alcohol-related liver disease (MetALD) who consumed increased alcohol (30-60 g/d). Advanced fibrosis was defined as a fibrosis-4 index (FIB-4) ≥ 2.67, and FIB-4 ≥ 1.30 indicated an intermediate/high probability of hepatic fibrosis. Logistic regression models were used to assess the association between alcohol consumption and hepatic fibrosis, and analyze the modification effect of body mass index (BMI) and waist-to-hip ratio (WHR) on the association. Propensity score matching method was used to test the robustness of the regression results. Results Compared with non-drinkers, both moderate (OR = 3.02, 95% CI: 1.16-10.31) and increased alcohol consumption (OR = 4.64, 95% CI: 1.60-16.82) were significantly associated with an increased risk of advanced fibrosis in males with MASLD. Additionally, moderate (OR = 1.33, 95% CI: 1.07-1.66) and increased drinking (OR = 1.74, 95% CI: 1.28-2.34) were associated with intermediate/high probability of hepatic fibrosis, with similar results from logistic regression analysis in propensity score-matched cases. Trend analysis revealed the risk of hepatic fibrosis increased with increasing alcohol intake (FIB-4 ≥ 1.30, p for trend < 0.001; FIB-4 ≥ 2.67, p for trend = 0.007). Further subgroup analysis showed that the association between moderate drinking and intermediate/high probability of hepatic fibrosis was predominantly observed in males with BMI ≥ 23 kg/m2 (OR = 1.35, 95% CI: 1.08-1.69) and those with WHR ≥ 0.9 (OR = 1.40, 95% CI: 1.11-1.78). Conclusion In China, moderate alcohol intake may heighten the risk of hepatic fibrosis in males with MASLD who are overweight/obese or have abdominal obesity. Moreover, males with MetALD may have a higher risk of fibrosis compared to those with pure MASLD.
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Affiliation(s)
- Mao Li
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Bin Yu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoli Zhang
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Jia Pan
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Lei Tang
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Yi Zhang
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Ruixin Wang
- North Sichuan Medical College, Nanchong, Sichuan, China
| | - Honglian Zeng
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Shujuan Yang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
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Thallapureddy K, Twitchell D, Ott K, Pedicone LD, Owo C, Kumar N, Gelfond J, Shankar N, Goros M, Kwok D, Liles A, Ozguc F, Kazi I, Nguyen H, Lawitz E, Tsai E, Rodas F, Landaverde CE, Poordad F. The accuracy of FibroScan, FIB-4, and nonalcoholic fatty liver disease fibrosis score in predicting biopsy-defined fibrosis and steatosis across all fibrosis stages in patients with metabolic dysfunction associated steatotic liver disease. Medicine (Baltimore) 2025; 104:e42016. [PMID: 40295262 PMCID: PMC12040034 DOI: 10.1097/md.0000000000042016] [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: 06/24/2024] [Revised: 03/05/2025] [Accepted: 03/14/2025] [Indexed: 04/30/2025] Open
Abstract
Liver biopsy is the gold standard for quantifying steatosis and fibrosis. It is unclear how noninvasive tests (NITs) accurately correlate to liver biopsy. The aim of this study was to characterize patients with metabolic-associated steatotic liver disease who underwent liver biopsy in South Texas and had at least 1 contemporaneous NIT result available to determine the accuracy of NITs as compared to liver biopsy in accurately staging fibrosis and steatosis. The study included 460 patients with liver biopsy and at least 1 NIT. Data captured was based on standard of care and was non-interventional in nature. Performance characteristics of the NITs were analyzed based on the degree of fibrosis defined by liver biopsy. The majority of patients were female (66.4%), middle-aged (51 years), and Hispanic/Latino (73.3%). In patients with F3/F4 fibrosis, FibroScan accurately identified only 45.9% with advanced fibrosis. Even when using society recommended results from fibrosis-4 combined with FibroScan, concordance with liver biopsy was only reported in 68.9% of patients. Patients with biopsy-defined advanced steatosis (S3) were identified as having advanced steatosis by FibroScan controlled attenuation parameter score in 89.7% of patients; however, controlled attenuation parameter score overly predicted advanced steatosis in 81.4% with biopsy-defined S1/S2 steatosis. NITs should be used as first line to assess steatosis and fibrosis; however, the optimal combination of these tests has not been elucidated and properly compared to liver biopsy to assess true diagnostic accuracy. Until the optimal set of NITs are found, any diagnostic or clinical inconsistencies should be resolved with liver biopsy to avoid staging errors, particularly underestimating fibrosis in those with advanced disease.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - Iqra Kazi
- UT Health San Antonio, San Antonio, TX
| | - Harry Nguyen
- UT Health San Antonio, San Antonio, TX
- Texas Liver Institute, San Antonio, TX
| | - Eric Lawitz
- UT Health San Antonio, San Antonio, TX
- Texas Liver Institute, San Antonio, TX
| | - Eugenia Tsai
- UT Health San Antonio, San Antonio, TX
- Texas Liver Institute, San Antonio, TX
| | - Fabian Rodas
- UT Health San Antonio, San Antonio, TX
- Texas Liver Institute, San Antonio, TX
| | | | - Fred Poordad
- UT Health San Antonio, San Antonio, TX
- Texas Liver Institute, San Antonio, TX
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Huang L, Luo Y, Zhang L, Wu M, Hu L. Machine learning-based disease risk stratification and prediction of metabolic dysfunction-associated fatty liver disease using vibration-controlled transient elastography: Result from NHANES 2021-2023. BMC Gastroenterol 2025; 25:255. [PMID: 40229697 PMCID: PMC11998142 DOI: 10.1186/s12876-025-03850-x] [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: 01/22/2025] [Accepted: 04/03/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease and represents a significant public health issue. Nevertheless, current risk stratification methods remain inadequate. The study aimed to use machine learning in the identification of significant features and the development of a predictive model to determine its usefulness in discrimination of MAFLD's risk stratification (low, moderate, and high) in adults. METHODS The data of the 2021-2023 NHANES database were analyzed. Vibration-controlled transient elastography measurements, including controlled attenuation parameter for the evaluation of steatosis and liver stiffness for the evaluation of fibrosis, were used for risk stratification. The participants were grouped into low-risk, moderate-risk, and high-risk groups based on specific criteria. Feature selection was conducted through Least Absolute Shrinkage and Selection Operator (LASSO) regression and random forest classification. RESULTS A total of 4,227 participants were included in the study. There were 16 significant predictors identified by LASSO regression, among which the top 10 predictors were demographic (age, gender, race, hypertension history), clinical (body mass index, waist circumference, hemoglobin, glycohemoglobin, lymphocyte count), and education level. The area under the receiver operating characteristic curve (AUC) of the random forest model in the validation set was 0.80, and the individual AUC was 0.83, 0.66 and 0.79 for the low-, moderate-, and high-risk groups, respectively. CONCLUSION Our machine learning model has excellent performance in stratification of risk for MAFLD with readily available clinical and demographic parameters. This model could be employed as a valuable screening tool to refer high-risk patients for further hepatological evaluation.
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Affiliation(s)
- Liqiong Huang
- Department of Ultrasound, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Sichuan Province, No. 18 Wanxiang North Road, High Tech Zone, Chengdu, China
| | - Yu Luo
- Department of Ultrasound, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Sichuan Province, No. 18 Wanxiang North Road, High Tech Zone, Chengdu, China
| | - Li Zhang
- Department of Ultrasound, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Sichuan Province, No. 18 Wanxiang North Road, High Tech Zone, Chengdu, China
| | - Mengqi Wu
- Department of Ultrasound, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Sichuan Province, No. 18 Wanxiang North Road, High Tech Zone, Chengdu, China
| | - Lirong Hu
- Department of Ultrasound, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Sichuan Province, No. 18 Wanxiang North Road, High Tech Zone, Chengdu, China.
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Sun Z, Zhang J, Duan J, Wang Q, Yun Z, Lin J, Yang Y, Zuo W, Wang Z, Xiong X, Yao K. Cross-sectional study on the association between the fibrosis-4 index and co-occurring myocardial infarction in Chinese patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2025; 16:1551472. [PMID: 40144298 PMCID: PMC11936788 DOI: 10.3389/fendo.2025.1551472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Background Previous studies indicated that the Fibrosis-4 Index (FIB-4), an evaluation metric for liver fibrosis, is associated with adverse outcomes in coronary artery disease. However, the correlation between FIB-4 and myocardial infarction (MI) in Chinese patients with Type 2 Diabetes Mellitus (T2DM) has not been well-defined. Thus, this study aims to elucidate the association between FIB-4 and MI in Chinese T2DM patients. Methods Cross-sectional data were collected from T2DM patients at two hospitals in China, designated as the discovery and validation centers. The exposure variable, FIB-4 index, was derived from patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. This index was stratified into four distinct clusters via k-means clustering analysis. The primary outcome was defined as the incidence of co-occurring MI. Logistic and restricted cubic spline regression was conducted to assess the association between the FIB-4 index and MI in Chinese T2DM patients. Results In the discovery phase, data were analyzed from 2,980 T2DM patients, including 1,114 females (37.38%), with 58 years average age (SD: 10.4). Among them, 190 were also MI patients. Based on the fully adjusted logistic regression analysis, the odds ratio (OR) for the second cluster was 1.00 (95% CI, 0.60-1.40); for the third cluster, it was 1.94 (95% CI, 1.32-2.57), and for the poorest controlled cluster it was 16.18 (95% CI, 14.97-17.39) in comparison to the best-controlled cluster of FIB-4. Restricted cubic spline regression revealed a linear relationship between the FIB-4 index and MI risk. Subgroup analysis demonstrated that this association was significant in elderly adults, females with high BMI, and those with comorbidities such as hypertension, coronary artery disease, and chronic heart failure. These findings yield consistent results in the validation set (n = 224). Conclusions Among Chinese patients with T2DM, elevated FIB-4 levels have been independently associated with MI, particularly among females and individuals with concomitant hypertension. Consequently, the FIB-4 index is anticipated to serve as a promising tool for early detection and risk stratification in this population.
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Affiliation(s)
- Ziyi Sun
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Jin Zhang
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Jinlong Duan
- Department of Andrology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qingqing Wang
- Department of Internal Medicine, Eye Hospital China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhangjun Yun
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jianguo Lin
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuhan Yang
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - WenXi Zuo
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zeqi Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Xingjiang Xiong
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Kuiwu Yao
- Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Academic Administration Office, China Academy of Chinese Medical Sciences, Beijing, China
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Buchanan RM, Reinson T, Bilson J, Woodland H, Nwoguh C, Cooper K, Harris S, Malone K, Byrne CD. Screening to identify people with type 2 diabetes at risk of liver cancer in primary care: a randomised controlled trial protocol. BMJ Open 2025; 15:e088043. [PMID: 40050060 PMCID: PMC11887308 DOI: 10.1136/bmjopen-2024-088043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 02/07/2025] [Indexed: 03/09/2025] Open
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is expected to become the third most common cause of cancer death worldwide by 2030. The increase in HCC is in large part due to the rising prevalence of risk factors such as type 2 diabetes mellitus (T2DM). Up to 1 in 20 people living with T2DM have liver cirrhosis, and they have a 1% to 2% incidence of HCC per year. Patients with cirrhosis enter surveillance for HCC to identify early-stage, curable tumours. A diagnosis of T2DM does not mandate testing to identify patients with cirrhosis, with testing restricted to those with additional risks. There has never been a trial and nested cost-effectiveness evaluation comparing screening all patients with T2DM for cirrhosis against usual care. METHODS AND ANALYSIS The study will use a multi-centre, unblinded individual randomised controlled trial design. The aim will be to determine the effectiveness and cost-effectiveness of screening all adults with T2DM to identify those at high risk of HCC. The recruitment strategy has been supported by patient and public involvement (PPI). Participants will be identified via an automated search of primary care records and invited to participate via text. 320 participants will be randomised for screening. The screening will include measurement of bio-markers for liver fibrosis (ELF and Fib-4) and vibration-controlled transient elastography. Another 320 participants will be randomised to standard care. Demographic and medical history data will be collected at baseline from all participants. Outcome data will be collected remotely from healthcare records. The primary outcome is the proportion of participants in each arm who are referred to HCC surveillance following testing for liver disease within 12 months of randomisation. The results will be used to calculate the incremental cost-effectiveness ratio of screening via a Markov model. ETHICS AND DISSEMINATION The results of this study will be presented directly to National Health Service England. Additional dissemination via conference proceedings and publication will be supported by our PPI team. Ethical approval was granted by the West of Scotland Research Ethics Service on 2 August 2023, REC reference 23/WS/0102. TRIAL REGISTRATION NUMBER ISRCTN17017677.
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Affiliation(s)
- Ryan M Buchanan
- University of Southampton Faculty of Medicine, Southampton, UK
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Tina Reinson
- Clinical and Experimental Sciences Division, University of Southampton Faculty of Medicine, Southampton, UK
| | - Josh Bilson
- University of Southampton Faculty of Medicine, Southampton, UK
| | - Hazel Woodland
- Salisbury District Hospital NHS Foundation Trust, Salisbury, UK
| | - Chinonso Nwoguh
- University of Southampton Faculty of Medicine, Southampton, UK
| | - Keith Cooper
- Southampton Health Technology Assessment Centre, University of Southampton, Southampton, UK
| | - Scott Harris
- University of Southampton Faculty of Medicine, Southampton, UK
| | | | - Christopher D Byrne
- University of Southampton Faculty of Medicine, Southampton, UK
- NIHR Southampton Biomedical Research Centre, Southampton, UK
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11
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Xiang F, Mao HX, Xu Y, Ge XX. Potential association of neutrophil-albumin ratio with non-alcoholic fatty liver disease: A cross-sectional study based on NHANES. Shijie Huaren Xiaohua Zazhi 2025; 33:122-130. [DOI: 10.11569/wcjd.v33.i2.122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/30/2024] [Accepted: 02/20/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem in the world. Exploring objective biomarkers for the prevention, monitoring, and clinical evaluation of NAFLD is of guiding significance for clinical targeted prevention and treatment. There is a complex interaction between inflammation and NAFLD. Exploring NAFLD-related inflammatory markers is helpful for elucidating its pathogenic mechanism.
AIM To explore the potential association between the inflamma-tory marker neutrophil to albumin ratio (NAR) and NAFLD based on the National Health and Nutrition Examination Survey (NHANES) database.
METHODS The participant data set of the NHANES database from 2017 to 2018 was selected. They were divided into NAFLD group and non-NAFLD group according to the occurrence of NAFLD or not. The clinical data of the two groups were compared. Logistic regression analysis was used to analyze the relationship between NAR and NAFLD, and restricted cubic spline (RCS) and threshold effect analysis were performed to explore the potential turning point.
RESULTS A total of 4526 participants were enrolled, including 1503 patients with NAFLD. The NAR level in the NAFLD group was significantly higher than that of the non-NAFLD group (P < 0.05). There were also significant differences in gender, age, body mass index, smoking status, hypertension, antihypertensive drugs, diabetes, hypoglycemic agents, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, uric acid, triglyceride, and total cholesterol between the two groups (P < 0.05 for), and these variables were therefore included in the adjusted model analyses. In model 1 without any adjustment, NAR levels were associated with the risk of NAFLD (OR = 2.154). In the model 2 (OR = 1.375), model 3 (OR = 1.693), and model 4 (OR = 1.817) adjusting for some variables, their independent association still existed. RCS curve analysis showed that there was a nonlinear relationship between NAR and NAFLD (Pfor overall < 0.001, Pfor nonlinear < 0.001). Threshold effect analysis showed that the inflection point of NAR influencing NAFLD risk was 1.436, and when NAR was lower than 1.436, the risk of NAFLD occurrence increased by 3.304 times for each additional unit of NAR (OR = 3.304; 95% confidence interval: 2.649-4.122; P < 0.001). However, this study did not found the potential value of NAR in distinguishing non-alcoholic steatohepatitis.
CONCLUSION The levels of NAR show an independent association with NAFLD. When NAR is lower than 1.436, the risk of NAFLD increases with the increase of NAR level.
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Affiliation(s)
- Fen Xiang
- Department of Surgery, Longquan People's Hospital, Lishui 323700, Zhejiang Province, China
| | - Hua-Xin Mao
- Department of Surgery, Longquan People's Hospital, Lishui 323700, Zhejiang Province, China
| | - Yu Xu
- Department of Surgery, Longquan People's Hospital, Lishui 323700, Zhejiang Province, China
| | - Xin-Xing Ge
- Department of Surgery, Longquan People's Hospital, Lishui 323700, Zhejiang Province, China
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Åsberg A, Lian IA, Løfblad L, Mikkelsen G. Personalized risk assessment of advanced liver fibrosis in patients with MASLD. J Hepatol 2025:S0168-8278(25)00093-5. [PMID: 39983835 DOI: 10.1016/j.jhep.2025.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/03/2025] [Accepted: 02/03/2025] [Indexed: 02/23/2025]
Affiliation(s)
- Arne Åsberg
- Department of Clinical Chemistry, St. Olav's Hospital, POB 3250 Torgarden, 7006 Trondheim, Norway.
| | - Ingrid Alsos Lian
- Department of Clinical Chemistry, St. Olav's Hospital, POB 3250 Torgarden, 7006 Trondheim, Norway and Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, POB 8900, 7491 Trondheim, Norway
| | - Lena Løfblad
- Department of Clinical Chemistry, St. Olav's Hospital, POB 3250 Torgarden, 7006 Trondheim, Norway and Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, POB 8900, 7491 Trondheim, Norway
| | - Gustav Mikkelsen
- Department of Clinical Chemistry, St. Olav's Hospital, POB 3250 Torgarden, 7006 Trondheim, Norway and Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, POB 8900, 7491 Trondheim, Norway
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Mahmoud MR, Ibrahim S, Shahien MM, Alshammari AD, Alenazi FS, Alreshidi F, Aljadani A, Abdel Khalik A, Elhaj AH, Khalifa AM, Alreshidi HF, El-Horany HES, Said KB, Abdallah MH, Metwaly AA. Comparison Between the Impact of Diabetes Mellitus on Liver Diseases and Vice Versa Among Saudi and Egyptian Patients. Healthcare (Basel) 2025; 13:376. [PMID: 39997251 PMCID: PMC11855539 DOI: 10.3390/healthcare13040376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/28/2025] [Accepted: 02/06/2025] [Indexed: 02/26/2025] Open
Abstract
Background: The risk of dying from chronic liver diseases (CLDs) is two to three times higher for patients with diabetes (DM). Nonalcoholic fatty liver disease (NAFLD) is the primary cause of this increased risk, which has an etiology unrelated to alcohol or viruses. Previous research reported that diabetes and CLD are related, since they influence each other. Aim: Estimation of the impact of diabetes (DM) on liver diseases (LD), and of the impact of liver diseases on DM among Egyptian and Saudi patients. It is a descriptive and prospective analytical study design. The investigation was carried out in Saudi Arabia and Egypt at gastroenterology outpatient clinics. Methods: Prospective data were collected through face-to-face patient interviews during clinic visits between June 2021 and June 2023. The interviews covered the patients' basic characteristics and information on DM and LD. Certain laboratory tests were conducted on these patients, such as liver function, glucose level, lipid profile, INR, and prothrombin time. Results: The total of 2748 participants in this study included 1242 diabetic patients of both genders from Saudi Arabia and 1506 from Egypt. Most Saudis had between 10 and 20 years' duration of DM (35.5%), with HbA1c (7-10%) values of 47.8%, while the Egyptian patients had >20 years' duration of DM (39.8%), with HbA1c (7-10%) values of 49.8%. Regarding the impact of DM on the development of liver diseases, about 35.5% (Saudis) vs. 23.5% (Egyptians) had liver diseases due to DM, a significant difference (p-value = 0.011). Liver enzymes were increased in many of the Egyptian and Saudi patients (41.4% vs. 33%), while the presence of fatty liver (28.2% vs. 35.7%) and hepatocellular carcinoma (13.7% vs. 6.1%) were also significantly different (p-value = 0.047). While the impact of liver diseases on DM was observed more among Egyptian (59%) than among Saudi (46.4%) patients because of liver cirrhosis (HCV or HBV), known to be a reason for diabetes in Egyptians (27.9%) vs. Saudis (8.0%), a higher incidence of fatty liver leading to DM was observed in Saudis than in Egyptians (15.9% vs. 11.6%) (p-value = 0.000. Obesity was more prevalent among Saudi patients (63.8%) than among Egyptian patients (48.6%) (p-value = 0.019). Fewer Egyptians (about 65%) suffered from dyslipidemia than Saudis (about 80%). Higher INR and longer prothrombin times were observed in Egyptians (29.9% and 29.1%, respectively) than in Saudis (20.3% and 18.8%, respectively), with a significant difference between the two nations (p-value < 0.050). Conclusions: We may conclude that diabetes in most patients has a negative impact on the development of liver diseases (particularly fatty liver in Saudi patients). In addition, most liver diseases (liver cirrhosis) have a negative influence on the development of DM (more so in Egyptian patients). There is a link between DM and liver disease. In particular, liver cirrhosis and diabetes were found to influence each other. Therefore, correct medication, adherence to treatment, lifestyle modifications, successful cirrhosis control (in patients with liver diseases), and diabetic control (in diabetic patients) could lead to effective management of both diseases. The negative fallouts in the two cases were prompted by obesity, morbid eating, and poor quality of life.
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Affiliation(s)
- Madiha R. Mahmoud
- Department of Pharmacology, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia;
| | - Somia Ibrahim
- Department of Pediatrics, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia; (S.I.); (M.M.S.)
| | - Mona M. Shahien
- Department of Pediatrics, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia; (S.I.); (M.M.S.)
| | - Amal Daher Alshammari
- Department of Family and Community Medicine, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia; (A.D.A.); (F.A.); (A.H.E.); (H.F.A.)
| | - Fahaad S. Alenazi
- Department of Pharmacology, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia;
| | - Fayez Alreshidi
- Department of Family and Community Medicine, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia; (A.D.A.); (F.A.); (A.H.E.); (H.F.A.)
| | - Ahmed Aljadani
- Department of Psychiatry, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia;
| | - Ashraf Abdel Khalik
- Department of Intensive Care Unit, TBRI, Ministry of Higher Education and Scientific Research, Giza 12411, Egypt; (A.A.K.); (A.A.M.)
| | - Abeer H. Elhaj
- Department of Family and Community Medicine, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia; (A.D.A.); (F.A.); (A.H.E.); (H.F.A.)
| | - Amany M. Khalifa
- Medical Parasitology, Pathology Department, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia;
- Medical Parasitology Department, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt
| | - Hend Faleh Alreshidi
- Department of Family and Community Medicine, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia; (A.D.A.); (F.A.); (A.H.E.); (H.F.A.)
| | - Hemat El-Sayed El-Horany
- Department of Biochemistry, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia;
- Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Kamaleldin B. Said
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il 81422, Saudi Arabia;
- Genomics, Bioinformatics and Systems Biology, Carleton University, 1125 Colonel-By Drive, Ottawa, ON K1S 5B6, Canada
| | - Marwa H. Abdallah
- Department of Pharmaceutics, College of Pharmacy, University of Ha’il, Ha’il 81422, Saudi Arabia
| | - Amna A. Metwaly
- Department of Intensive Care Unit, TBRI, Ministry of Higher Education and Scientific Research, Giza 12411, Egypt; (A.A.K.); (A.A.M.)
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Lindfors A, Strandberg R, Hagström H. Screening for advanced liver fibrosis due to metabolic dysfunction-associated steatotic liver disease alongside retina scanning in people with type 2 diabetes: a cross-sectional study. Lancet Gastroenterol Hepatol 2025; 10:125-137. [PMID: 39675369 DOI: 10.1016/s2468-1253(24)00313-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND International guidelines suggest screening for advanced fibrosis due to metabolic dysfunction-associated steatotic liver disease in people with type 2 diabetes, but how to implement these guidelines in clinical care remains unclear. We hypothesise that examination with VCTE could be implemented simultaneously with retina scanning with a high acceptance rate in people with type 2 diabetes. METHODS In this cross-sectional study, we offered VCTE to people with type 2 diabetes referred to routine retina scanning in a large retina scanning facility in Stockholm, Sweden. We excluded people with type 1 diabetes, currently pregnant, with known liver disease, reporting high alcohol consumption, who did not speak Swedish, or younger than 18 years. Between Nov 6, 2020, and June 20, 2023, we conducted surveys with included participants and collected data from medical records on diabetes retinopathy, sex, and VCTE measurements. Increased liver stiffness was defined as at least 8·0 kPa, and possible advanced fibrosis as more than 12·0 kPa. Presence of metabolic dysfunction-associated steatotic liver disease was defined as a controlled attenuation parameter (CAP) value of 280 dB/m or higher. Participants with a liver stiffness measurement of at least 8·0 kPa or those with unreliable measurements were subsequently referred for a secondary evaluation at a liver specialist, including a follow-up liver stiffness measurement with VCTE. The primary outcome was the proportion of eligible people approached for screening who accepted. Secondary outcomes were the prevalence of elevated liver stiffness (≥8·0 kPa or >12·0 kPa), presence of metabolic dysfunction-associated steatotic liver disease, and the proportion of elevated liver stiffness readings at the first VCTE examination that were not elevated in the secondary evaluation with a liver specialist. Secondary outcomes were assessed in all participants who accepted screening, except false positives, which were assessed only in participants who had a second examination. FINDINGS 1301 participants were eligible to undergo assessment with VCTE, which was accepted by 1005 (77·2%). 973 (96·8%) participants had complete measurements, of whom 504 (51·8%) had CAP values of 280 dB/m or higher, indicating metabolic dysfunction-associated steatotic liver disease. Of 977 participants with reliable liver stiffness measurements, 154 (15·8%) had values of at least 8·0 kPa, suggestive of liver fibrosis, and 49 (5·0%) had values higher than 12·0 kPa, indicating possible advanced fibrosis. However, upon reassessment with a second VCTE after referral, 56 (45·2%) of 124 individuals had values less than 8·0 kPa. 74 (7·4%) of 1005 participants had a final liver stiffness of at least 8·0 kPa; 29 (2·9%) had values greater than 12·0 kPa. INTERPRETATION Simultaneous examination with VCTE alongside retina scanning had a high acceptance rate among people with type 2 diabetes and could be a strategy for case-finding of people with fibrosis due to metabolic dysfunction-associated steatotic liver disease. However, a high proportion of participants in our study with elevated liver stiffness measurement at the screening visit did not have an elevated liver stiffness measurement at secondary evaluation, suggesting false-positive findings were common. FUNDING Gilead Sciences, Pfizer, Region Stockholm, Åke Wiberg Foundation, and Bengt Ihre Foundation.
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Affiliation(s)
- Andrea Lindfors
- Division of Hepatology, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - Hannes Hagström
- Division of Hepatology, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
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Armstrong MJ, Okanoue T, Sundby Palle M, Sejling AS, Tawfik M, Roden M. Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials. Diabetes Obes Metab 2025; 27:710-718. [PMID: 39609879 DOI: 10.1111/dom.16065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 10/24/2024] [Accepted: 10/31/2024] [Indexed: 11/30/2024]
Abstract
AIMS Weight loss mediated by glucagon-like peptide-1 (GLP-1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP-1 analogue semaglutide. MATERIALS AND METHODS This was a post hoc analysis of data from three 48-72-week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy-confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre-type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations. RESULTS The overall mean weight change was -11.1 kg (-11.7%) and -0.7 kg (-0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (-10.2 kg; -10.8%), pre-type 2 diabetes (-9.8 kg; -10.2%) and no diabetes (-11.6 kg; -13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change. CONCLUSIONS People with MASLD/MASH had similar semaglutide-mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters.
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Affiliation(s)
- Matthew J Armstrong
- Liver Unit, Queen Elizabeth University Hospital, Birmingham, UK
- National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan
| | | | | | | | - Michael Roden
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
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Pose E, Piano S, Thiele M, Fabrellas N, Tsochatzis EA, Ginès P. Moving diagnosis of liver fibrosis into the community. J Hepatol 2025:S0168-8278(25)00063-7. [PMID: 39892822 DOI: 10.1016/j.jhep.2025.01.026] [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: 03/15/2024] [Revised: 01/15/2025] [Accepted: 01/23/2025] [Indexed: 02/04/2025]
Abstract
Chronic liver disease (CLD) is a leading cause of death worldwide, with alcohol consumption and metabolic risk factors accounting for the majority of cases of CLD in many developed countries. Currently, specific strategies for the early diagnosis of CLD are lacking and consequently most cases are diagnosed at an advanced stage, which is associated with negative consequences for disease management and prognosis. Screening for CLD is based on either detection of chronic viral hepatitis B and C, or detection of liver fibrosis in patients with steatotic liver disease related to alcohol or metabolic dysfunction. Non-invasive tools, including serological and imaging-based tests, can be used to detect liver fibrosis. Clinical practice guidelines recommend screening for liver fibrosis using algorithms that combine different non-invasive tests, with widely available but low accuracy tests, such as FIB-4, recommended as a first screening step in the primary care setting, and other tests with lower availability but higher accuracy, such as transient elastography or the enhanced liver fibrosis test, recommended as a second step. There are different pathways for early detection of patients with CLD from primary to specialised care, with primary care providers being key for early detection, management and referral of patients. In addition, interventions targeting metabolic risk factors and alcohol consumption should be carried out in collaboration between specialists and primary care. In this review, we describe liver fibrosis from the community perspective, highlighting gaps in knowledge on how to define the optimal combination of tests, target population, the ideal pathway of care for CLD, and how to increase implementation of programmes for early diagnosis of liver diseases in clinical practice.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Italy
| | - Maja Thiele
- FLASH Center for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark; Department for Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Núria Fabrellas
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain; Faculty of Nursing, University of Barcelona, Barcelona, Spain
| | - Emmanuel A Tsochatzis
- Sheila Sherlock Liver Unit, Royal Free Hospital, London, UK; UCL Institute of Liver and Digestive Health, University College London, UK
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Madrid, Spain; School of Medicine and Health Sciences. University of Barcelona. Barcelona. Catalonia, Spain.
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Strajhar P, Berzigotti A, Nilius H, Nagler M, Dufour JF. Estimating the prevalence of adults at risk for advanced hepatic fibrosis using FIB-4 in a Swiss tertiary care hospital. PLoS One 2025; 20:e0317629. [PMID: 39854322 PMCID: PMC11759403 DOI: 10.1371/journal.pone.0317629] [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: 10/21/2024] [Accepted: 12/31/2024] [Indexed: 01/26/2025] Open
Abstract
BACKGROUND & AIMS Chronic liver diseases pose a serious public health issue. Identifying patients at risk for advanced liver fibrosis is crucial for early intervention. The Fibrosis-4 score (FIB-4), a simple non-invasive test, classifies patients into three risk groups for advanced fibrosis. This study aimed to estimate the prevalence of patients at risk for advanced hepatic fibrosis at a Swiss tertiary care hospital by calculating the FIB-4 score in routine blood analysis. METHODS A retrospective study was conducted using data from 36,360 patients who visited outpatient clinics at eight main clinics of the University Hospital Bern in Switzerland. The data collection period ran from January 1st to December 31st, 2022. Patients attending the hepatology outpatient clinic were excluded. We then calculated the overall and clinic-specific prevalence of patients falling into the high risk category for advanced fibrosis according to FIB-4. RESULTS Among the 36,360 patients, 26,245 (72.2%) had a low risk of advanced fibrosis (FIB-4 <1.3), whereas 3913 (10.8%) and 2597 (7.1%) patients were flagged to have a high risk of advanced fibrosis (FIB-4 >2.67 and FIB-4 >3.25 respectively). Geriatrics and Cardiology had the highest proportions of patients at risk for advanced fibrosis over all clinics. CONCLUSIONS This study demonstrates a high prevalence of high FIB-4 score in a Swiss tertiary care hospital. The implementation of the automatically generated FIB-4 score in daily practice, not only in primary care, but also within tertiary care hospitals, could be crucial for early identification of outpatients at high risk of advanced liver fibrosis requiring further hepatological investigations.
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Affiliation(s)
- Petra Strajhar
- Master of Public Health, University Basel, University Bern & University Zurich, Zurich, Switzerland
| | - Annalisa Berzigotti
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Henning Nilius
- Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Michael Nagler
- Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Khan F, Dsouza S, Khamis AH, Abdul F, Farooqi MH, Sulaiman F, Mulla F, Al Awadi F, Hassanein M, Bayoumi R. Noninvasive Assessment of the Severity of Liver Fibrosis in MASLD Patients with Long-Standing Type 2 Diabetes. J Gen Intern Med 2025:10.1007/s11606-025-09348-2. [PMID: 39841343 DOI: 10.1007/s11606-025-09348-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 12/30/2024] [Indexed: 01/23/2025]
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), which have a reciprocal relationship compounded by obesity, are highly prevalent in the Middle East affecting morbidity, mortality, and healthcare costs. OBJECTIVE This study aimed to assess the severity of MASLD and liver fibrosis among adult Emirati patients with long-standing T2DM. DESIGN AND PARTICIPANTS This cross-sectional study used noninvasive methods to assess the severity of MASLD and fibrosis progression in an adult cohort of Emirati patients (N = 546) with a mean T2DM duration of 16 years. MAIN MEASURES Fatty liver infiltration was assessed by hepatic steatosis index (HSI), while fibrosis was assessed by the fibrosis-4 (FIB-4) index and aspartate aminotransferase/platelet ratio index (APRI). Of those, 108 patients were randomly subjected to ultrasound-based FibroScan® to assess controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). KEY RESULTS All patients had fatty liver with ~ 83% being categorized as having severe steatosis. Serum-based fibrosis biomarker panels detected significant liver fibrosis in ~ 2.5% of these patients. The APRI appeared to be more restrictive in detecting moderate fibrosis (1.5%) than the FIB-4 index (25.5%). CAP significantly correlated with the LSM, indicating that the two methods contributed to the same underlying pathophysiology. Liver steatosis was more severe in female patients, who were older and had a higher body mass index (BMI) than those with moderate or no significant fibrosis. They also had higher serum liver enzymes and were more likely to have age-related changes in kidney function. Interestingly, severity of both steatosis and fibrosis remained unaffected by age and duration of T2D except for fibrosis severity detected by FibroScan®. CONCLUSIONS This study highlights the critical need for routine screening of MASLD among Emirati patients with long-standing T2DM, given the high point prevalence of severe steatosis (~ 83%), predominantly among women in this population.
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Affiliation(s)
- Farooq Khan
- Hepatology, King's College Hospital London, Dubai, United Arab Emirates
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Stafny Dsouza
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Amar Hassan Khamis
- Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Fatima Abdul
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | | | - Fatima Sulaiman
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Fahad Mulla
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Fatheya Al Awadi
- Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates
| | - Mohammed Hassanein
- Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates
| | - Riad Bayoumi
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
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Kitsunai H, Shinozaki Y, Furusawa S, Kitao N, Ito M, Kurihara H, Oba-Yamamoto C, Takeuchi J, Nakamura A, Takiyama Y, Nomoto H. The Effects of Oral Semaglutide on Hepatic Fibrosis in Subjects with Type 2 Diabetes in Real-World Clinical Practice: A Post Hoc Analysis of the Sapporo-Oral SEMA Study. Pharmaceuticals (Basel) 2025; 18:129. [PMID: 39861190 PMCID: PMC11769496 DOI: 10.3390/ph18010129] [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: 12/20/2024] [Revised: 01/09/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated. METHODS A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired t-test or the Wilcoxon signed-rank test. RESULTS Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, p < 0.001) and FIB-4 index (from 1.04 to 0.96, p < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index. CONCLUSIONS The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes.
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Affiliation(s)
- Hiroya Kitsunai
- Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan; (H.K.); (Y.S.); (Y.T.)
| | - Yuka Shinozaki
- Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan; (H.K.); (Y.S.); (Y.T.)
| | - Sho Furusawa
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Hokkaido, Japan; (S.F.); (A.N.)
| | - Naoyuki Kitao
- Aoki Clinic, Internal Medicine, Sapporo 003-0023, Hokkaido, Japan;
| | - Miki Ito
- Kurihara Clinic, Internal Medicine, Sapporo 004-0053, Hokkaido, Japan; (M.I.); (H.K.)
| | - Hiroyoshi Kurihara
- Kurihara Clinic, Internal Medicine, Sapporo 004-0053, Hokkaido, Japan; (M.I.); (H.K.)
| | - Chiho Oba-Yamamoto
- Sapporo Thyroid and Diabetes Clinic, Internal Medicine, Sapporo 060-0807, Hokkaido, Japan; (C.O.-Y.); (J.T.)
| | - Jun Takeuchi
- Sapporo Thyroid and Diabetes Clinic, Internal Medicine, Sapporo 060-0807, Hokkaido, Japan; (C.O.-Y.); (J.T.)
| | - Akinobu Nakamura
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Hokkaido, Japan; (S.F.); (A.N.)
| | - Yumi Takiyama
- Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan; (H.K.); (Y.S.); (Y.T.)
| | - Hiroshi Nomoto
- Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan; (H.K.); (Y.S.); (Y.T.)
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Hokkaido, Japan; (S.F.); (A.N.)
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20
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He MY, Du XJ, Liu YM. Association between neutrophil-albumin ratio and ultrasound-defined metabolic dysfunction-associated fatty liver disease in U.S. adults: evidence from NHANES 2017-2018. BMC Gastroenterol 2025; 25:20. [PMID: 39833665 PMCID: PMC11744826 DOI: 10.1186/s12876-025-03612-9] [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: 07/05/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly prevalent, and systemic inflammation markers may play a role in its pathogenesis. This study aimed to investigate the relationship between neutrophil-albumin ratio (NAR) and MAFLD. METHODS This population-based study was performed using data from NHANES 2017-2018 and included 4526 individuals with a median age of 44 years old, and the males account for 46.13% (n = 2088). Ultrasound-defined MAFLD was diagnosed using a controlled attenuation parameter (CAP) threshold of ≥ 285 dB/m. Differences in baseline characteristics between patients with CAP ≥ 285 dB/m and < 285 dB/m were analyzed. A generalized additive model (GAM) and restricted cubic splines (RCS) were applied to explore the nonlinear relationship between NAR and CAP, followed by generalized linear models (GLMs). Threshold effect analysis was performed to identify the inflection point in the nonlinear relationship. CAP-related variables were ranked using XG Boost and random forest algorithms, and predictive models were developed and evaluated. RESULTS The study population included 1,503 patients with CAP ≥ 285 dB/m. NAR was significantly elevated in subjects with CAP ≥ 285 dB/m (P < 0.001), and nonlinear relationships between NAR and CAP were observed. NAR was positively associated with CAP in three GLMs, and this relationship remained after adjusting for confounding factors or dividing NAR into tertiles. Additionally, when NAR < 1.436, a one-unit rise in NAR was linked to a 3.304-fold increase in the risk of NAFLD (OR = 3.304, 95% CI: 2.649-4.122). The NAR-based random forest model showed the best predictive performance with AUC values of 0.978 (training) and 0.813 (validation). CONCLUSION NAR is positively associated with CAP, and the NAR-based random forest model is optimal for predicting MAFLD risk, highlighting the importance of NAR in predicting MAFLD.
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Affiliation(s)
- Ming-Yu He
- Ultrasonography Department, Longyan First Hospital, Longyan, 364300, Fujian, China
| | - Xin-Jie Du
- Thyroid and Breast Surgery Department, Longyan First Hospital, Longyan, 364300, Fujian, China
| | - Yi-Ming Liu
- Gastroenterology Department, Longyan First Hospital, No. 105 Jiuyi North Road, Xinluo District, Longyan, 364300, Fujian, China.
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Wang JK, Zhang D, Wang JF, Lu WL, Wang JY, Liang SF, Liu R, Jiang JX, Li HT, Yang X. Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes. World J Diabetes 2025; 16:99526. [PMID: 39817226 PMCID: PMC11718457 DOI: 10.4239/wjd.v16.i1.99526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/04/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND At present, the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent, to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes, the report is as follows. AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus (T2DM). METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis. Metabolic indicators were collected preoperatively, as well as at 3 and 6 months postoperative. The metabolic indicators analyzed included body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), 2-hour blood glucose (PBG), glycated hemoglobin (HbA1c), fasting C-peptide, 2-hour C-peptide (PCP), fasting insulin (Fins), 2-hour insulin (Pins), insulin resistance index (HOMA-IR), β Cellular function index (HOMA-β), alanine aminotransferase, aspartate aminotransferase, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein, and uric acid (UA) levels. RESULTS SBP, DBP, PBG, HbA1c, LDL-C, and TG were all significantly lower 3 months postoperative vs preoperative values; body weight, BMI, SBP, DBP, FBG, PBG, HbA1c, TC, TG, UA, and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months; and PCP, Fins, Pins, and HOMA-β were all significantly higher 6 months postoperative vs at 3 months (all P < 0.05). CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.
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Affiliation(s)
- Ji-Kui Wang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Di Zhang
- Department of Health Management Center, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Jin-Feng Wang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Wan-Lin Lu
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Jing-Yuan Wang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Shi-Feng Liang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Ran Liu
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Jing-Xin Jiang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Hong-Tao Li
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Xuan Yang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
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Takamiya Y, Imanaga C, Abe I, Kobayashi K, Ike A, Kawamura A, Urata H. Long-term renoprotective effect of luseogliflozin in type 2 diabetes patients: CHikushi Anti-diabetes mellitus Trial-Lusefi (CHAT-Lu). Drug Discov Ther 2025; 18:336-342. [PMID: 39756883 DOI: 10.5582/ddt.2024.01086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
Several sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to have beneficial effects on renal function in patients with type 2 diabetes. However, the long-term effects of luseogliflozin, an SGLT2 inhibitor, remain uncertain in real-world settings. This multicenter, open-label, prospective observational study evaluated the long-term effects of luseogliflozin on renal function in Japanese patients with type 2 diabetes. Fifty-four outpatients initiated on luseogliflozin at Fukuoka University Chikushi Hospital or associated clinics were enrolled from April 2018 to December 2019, with 46 patients included in the final analysis set. The primary outcome was the change in estimated glomerular filtration rate (eGFR) from baseline to 104 weeks, and secondary outcomes included the change in eGFR at week 52 and changes in body weight and blood and urinary parameters at 52 and 104 weeks. The mean duration of diabetes was 8.1 years. Baseline eGFR was 75.8 ± 17.4 mL/min/1.73m2, and no decline in eGFR was observed from baseline to 104 weeks. Decline in eGFR was suppressed in the two groups stratified by baseline eGFR (< 60 and ≥ 60 mL/min/1.73m2). No changes were noted in urinary albumin excretion rate. Blood glucose, body weight, blood pressure, liver function, and uric acid levels showed significant improvements. There were four adverse events, but no serious adverse events closely related to luseogliflozin treatment. In type 2 diabetes patients, 2-year treatment with luseogliflozin provided beneficial metabolic effects and improved the rate of decline in eGFR, suggesting a renal protective effect.
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Affiliation(s)
- Yosuke Takamiya
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Chiyori Imanaga
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Ichiro Abe
- Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Kunihisa Kobayashi
- Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Amane Ike
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Akira Kawamura
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Hidenori Urata
- Department of Cardiovascular Diseases, Fukuoka University Chikushi Hospital, Fukuoka, Japan
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Miura D, Suenaga H, Hiwatashi R, Mabu S. Liver fibrosis stage classification in stacked microvascular images based on deep learning. BMC Med Imaging 2025; 25:8. [PMID: 39773130 PMCID: PMC11706143 DOI: 10.1186/s12880-024-01531-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Monitoring fibrosis in patients with chronic liver disease (CLD) is an important management strategy. We have already reported a novel stacked microvascular imaging (SMVI) technique and an examiner scoring evaluation method to improve fibrosis assessment accuracy and demonstrate its high sensitivity. In the present study, we analyzed the effectiveness and objectivity of SMVI in diagnosing the liver fibrosis stage based on artificial intelligence (AI). METHODS This single-center, cross-sectional study included 517 patients with CLD who underwent ultrasonography and liver stiffness testing between August 2019 and October 2022. A convolutional neural network model was constructed to evaluate the degree of liver fibrosis from stacked microvascular images generated by accumulating high-sensitivity Doppler (i.e., high-definition color) images from these patients. In contrast, as a method of judgment by the human eye, we focused on three hallmarks of intrahepatic microvessel morphological changes in the stacked microvascular images: narrowing, caliber irregularity, and tortuosity. The degree of liver fibrosis was classified into five stages according to etiology based on liver stiffness measurement: F0-1Low (< 5.0 kPa), F0-1High (≥ 5.0 kPa), F2, F3, and F4. RESULTS The AI classification accuracy was 53.8% for a 5-class classification, 66.3% for a 3-class classification (F0-1Low vs. F0-1High vs. F2-4), and 83.8% for a 2-class classification (F0-1 vs. F2-4). The diagnostic accuracy for ≥ F2 was 81.6% in the examiner's score assessment, compared with 83.8% in AI assessment, indicating that AI achieved higher diagnostic accuracy. Similarly, AI demonstrated higher sensitivity and specificity of 84.2% and 83.5%, respectively. Comparing human judgement with AI judgement, the AI analysis was a superior model with a higher F1 score in the 2-class classification. CONCLUSIONS In detecting significant fibrosis (≥ F2) using the SMVI method, AI-based assessments are more accurate than human judgement; moreover, AI-based SMVI analysis eliminating human subjectivity bias and determining patients with objective fibrosis development is considered an important improvement.
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Affiliation(s)
- Daisuke Miura
- Department of Ultrasound and Clinical Laboratory, Fukuoka Tokushukai Hospital, Fukuoka, 816-0864, Japan
- Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, 755-8508, Japan
| | - Hiromi Suenaga
- Department of Laboratory Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, 755-8508, Japan.
| | - Rino Hiwatashi
- Department of Ultrasound and Clinical Laboratory, Fukuoka Tokushukai Hospital, Fukuoka, 816-0864, Japan
| | - Shingo Mabu
- Department of Information Science and Engineering, Graduate School of Sciences and Technology for Innovation, Yamaguchi University, Yamaguchi, 755-8611, Japan
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Liang Z, Huang R, Zhang L. Correlation between hepatic steatosis severity diagnosed by ultrasound and metabolic indexes in elderly patients with MAFLD. Front Med (Lausanne) 2025; 11:1467773. [PMID: 39839645 PMCID: PMC11747716 DOI: 10.3389/fmed.2024.1467773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 12/23/2024] [Indexed: 01/23/2025] Open
Abstract
Objective To explore the connection between metabolic parameters and the severity of hepatic steatosis determined through ultrasound in elderly individuals with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods 4,663 senior individuals who were 65 years of age or older were included in this research. They were examined physically at the Ninghai Street Community Health Service Center in Yantai City between June 7, 2021, and October 15, 2021. There were two categories of individuals identified: the MAFLD group (n = 2,985) and the non-MAFLD group (n = 1,678). Based on liver ultrasonography results, individuals in the MAFLD group were further separated into three groups: mild (n = 2,104), moderate (n = 766), and severe (n = 115). To identify indicators of risk for the severity of hepatic steatosis, metabolic data was contrasted between the groups employing logistic regression. Results In comparison to the non-MAFLD group, the MAFLD group showed significantly elevated levels of body mass index (BMI), blood pressure, gender, age, lipid profile, alanine transaminase (ALT), and fasting blood glucose (FBG; p < 0.05). Among individuals with MAFLD, there was a positive correlation between BMI, FBG, ALT, and aspartate transaminase (AST) levels and the severity of hepatic steatosis (p < 0.05). Logistic regression analysis indicated that BMI, female gender, FBG, ALT, triglycerides (TG), and serum uric acid (SUA) constituted risk factors for increased severity of hepatic steatosis in MAFLD. Conclusion The severity of hepatic steatosis in elderly MAFLD patients is significantly correlated with female gender, BMI, ALT, FBG, TG, and SUA.
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Affiliation(s)
| | | | - Lingyun Zhang
- General Practice Department, Binzhou Medical University, Yantai, Shandong, China
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Bilal A, Pratley R. Diabetes and cardiovascular disease in older adults. Ann N Y Acad Sci 2025; 1543:42-67. [PMID: 39666834 DOI: 10.1111/nyas.15259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
An aging population combined with a rapidly increasing prevalence of diabetes foreshadows a global epidemic of cardiovascular and kidney disease that threatens to halt improvements in life and health-span and will have particularly severe consequences in older adults. The management of diabetes has been transformed with the recent development of newer anti-hyperglycemic agents that have demonstrated superior efficacy. However, the utility of these drugs extends beyond glycemic control to benefits for managing obesity, cardiovascular disease (CVD), chronic kidney disease, and heart failure. Numerous cardiovascular and kidney outcomes trials of these drugs have played an instrumental role in shaping current guidelines for the management of diabetes and CVD. Older adults with diabetes are diverse in terms of their comorbidities, diabetic complications, and cognitive and functional status. Therefore, there is an unmet need for personalized management of diabetes and CVD in this population. In this review, we provide an overview of the epidemiological burden and management of diabetes and CVD in older adults. We then focus on randomized cardiovascular and kidney outcome trials with anti-hyperglycemic agents to propose an evidence-based approach to the management of diabetes in older adults with high risk of cardiovascular and kidney disease.
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Affiliation(s)
- Anika Bilal
- AdventHealth Translational Research Institute, Orlando, Florida, USA
| | - Richard Pratley
- AdventHealth Translational Research Institute, Orlando, Florida, USA
- AdventHealth Diabetes Institute, Orlando, Florida, USA
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Yaribeygi H, Kashian K, Moghaddam KI, Karim SR, Bagheri N, Karav S, Jamialahmadi T, Rizzo M, Sahebkar A. Hepatic effects of GLP-1 mimetics in diabetic milieu: A mechanistic review of involved pathways. J Diabetes Complications 2025; 39:108928. [PMID: 39644538 DOI: 10.1016/j.jdiacomp.2024.108928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 11/25/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
Patients with diabetic are at a higher risk of developing hepatic disorders compared to non-diabetic individuals. This increased risk can be attributed to the diabetic environment, which triggers and exacerbates harmful pathways involved in both diabetic complications and hepatic disorders. Therefore, it is important to consider the use of antidiabetic agents that offer benefits beyond glycemic control and have positive effects on liver tissues. Glucagon-like peptide-1 (GLP-1) mimetics are a novel class of antidiabetic medications known for their potent blood sugar-lowering effects. Emerging evidence suggests that these drugs also have favorable effects on the liver. However, the precise effects and underlying mechanisms are not yet fully understood. In this review, we aim to provide a mechanistic perspective on the liver benefits of GLP-1 mimetics and outline the mediating mechanisms involved.
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Affiliation(s)
- Habib Yaribeygi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
| | - Kiana Kashian
- Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
| | | | | | - Narges Bagheri
- Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale 17100, Turkey
| | - Tannaz Jamialahmadi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Manfredi Rizzo
- School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Italy; Department of Biochemistry, Mohamed Bin Rashid University, Dubai, United Arab Emirates
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Chen L, Wu L, Zhang L, Sun B, Wu W, Lei Y, Zhu L, Sun T, Liang B, Zhao H, Zheng C. Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study. Int J Surg 2025; 111:828-838. [PMID: 38935094 PMCID: PMC11745749 DOI: 10.1097/js9.0000000000001872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown antitumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. MATERIALS AND METHODS This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and nonmetformin groups while competing risk regression was performed to assess cancer-specific death. RESULTS Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with a mean age of 59.6 (10.3) years received metformin, and 164 patients (139 male patients and 25 female patients) with a mean age of 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P <0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P <0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P <0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P =0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. CONCLUSION Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.
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Affiliation(s)
- Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Linxia Wu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Lijie Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, People’s Republic of China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Wenlong Wu
- Department of Interventional Radiology, Chegu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Yu Lei
- Department of Interventional Radiology, Chegu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Chegu Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Huangxuan Zhao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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ElSayed NA, McCoy RG, Aleppo G, Bajaj M, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Cusi K, Echouffo-Tcheugui JB, Ekhlaspour L, Fleming TK, Garg R, Khunti K, Lal R, Levin SR, Lingvay I, Matfin G, Napoli N, Pandya N, Parish SJ, Pekas EJ, Pilla SJ, Pirih FQ, Polsky S, Segal AR, Jeffrie Seley J, Stanton RC, Verduzco-Gutierrez M, Younossi ZM, Bannuru RR. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S59-S85. [PMID: 39651988 PMCID: PMC11635044 DOI: 10.2337/dc25-s004] [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: 12/14/2024]
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Ali SMJ, Lai M. Metabolic Dysfunction-Associated Steatotic Liver Disease. Ann Intern Med 2025; 178:ITC1-ITC16. [PMID: 39805112 DOI: 10.7326/annals-24-02933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in the United States. It is characterized by steatosis in the liver and is potentially reversible. Risk factors include obesity, type 2 mellitus, and other metabolic disorders. Metabolic dysfunction-associated steatohepatitis (MASH), a more severe form of MASLD, puts patients at risk for cirrhosis, liver decompensation, and liver cancer. Diet, exercise, and weight loss are the cornerstones of management. Although only 1 medication has been approved for treatment of MASH, other pharmacotherapies and surgeries that aid weight loss and optimize metabolic risk factors can be used. Early diagnosis and intervention are important to prevent progression to cirrhosis and its complications, including cancer.
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Affiliation(s)
- Sajjadh M J Ali
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (S.M.J.A., M.L.)
| | - Michelle Lai
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (S.M.J.A., M.L.)
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Pramukti H, Yunihastuti E, Gani RA, Rinaldi I, Hasan I, Maria S. Non-alcoholic fatty liver disease among people living with HIV on long-term antiretroviral therapy in Indonesia: Prevalence and related factors. SAGE Open Med 2024; 12:20503121241292678. [PMID: 39713267 PMCID: PMC11660071 DOI: 10.1177/20503121241292678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 10/03/2024] [Indexed: 12/24/2024] Open
Abstract
Background/objectives As people with human immunodeficiency virus experience longer life expectancy, other causes of morbidity and mortality are being increasingly identified. The incidence of non-alcoholic fatty liver disease has recently been on the rise in Indonesia. People with human immunodeficiency virus on antiretroviral therapy are also at an increased risk of having non-alcoholic fatty liver disease. The study aimed to define the prevalence and factors associated with non-alcoholic fatty liver disease in people with human immunodeficiency virus on stable antiretroviral therapy. Methods A cross-sectional study of people with human immunodeficiency virus, on antiretroviral therapy, age younger than 18 years old, and without hepatitis co-infection was conducted at the human immunodeficiency virus Integrated Clinic Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Non-alcoholic fatty liver disease was diagnosed using transient elastography with associated controlled attenuation parameter examination (diagnostic cutoff: 238 db/m). A logistic regression test with Poisson regression was used to evaluate factors associated with non-alcoholic fatty liver disease. Results One hundred and five people with human immunodeficiency virus were included, with a median age of 39 years and 65.7% were men. The prevalence of non-alcoholic fatty liver disease was 52.4%. Factors related to non-alcoholic fatty liver disease were hypertension (aPR: 1.49, 95% CI: 1.03-2.14, p = 0.033) and triglyceride levels (aPR: 1.001, 95% CI: 1.000-1.002, p = 0.024). No human immunodeficiency virus-specific variables were associated with non-alcoholic fatty liver disease. Conclusions More than half of Indonesian people with human immunodeficiency virus on antiretroviral therapy in this study were found to have non-alcoholic fatty liver disease. Hypertension and increased triglyceride levels were related to non-alcoholic fatty liver disease. Screening for non-alcoholic fatty liver disease should be implemented as a means of early intervention and to prevent complications.
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Affiliation(s)
- Hikmat Pramukti
- Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Evy Yunihastuti
- Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Rino A Gani
- Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Ikhwan Rinaldi
- Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Irsan Hasan
- Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Suzy Maria
- Faculty of Medicine, Department of Internal Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia
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Householder S, Loza AJ, Gupta V, Doolittle BR. Using Panel Management to Identify Adult Patients With High-Risk Metabolic Dysfunction-Associated Steatotic Liver Disease/Metabolic Dysfunction-Associated Steatohepatitis Fibrosis in a Primary Care Clinic: A Pilot Study. Perm J 2024; 28:38-47. [PMID: 39444281 PMCID: PMC11648331 DOI: 10.7812/tpp/24.094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
BACKGROUND As rates of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) rise, national organizations have released new guidance for primary care-driven detection of patients with advanced fibrosis who are most likely to have clinically relevant morbidity. Yet time constraints, workflow, and practitioner awareness limit integration of risk identification into clinical care. MATERIALS AND METHODS At the authors' primary care clinic, they implemented a panel management strategy that utilized the electronic health record to identify patients older than 35 years of age at risk for MASLD fibrosis with abnormal Fibrosis-4 (Fib-4) scores. Using a proactive model, these patients were offered elastography-based screening and follow-up appointments focused on metabolic health, with referrals to subspecialty care when indicated. RESULTS Of 855 patients older than 35 years of age, 384 were identified as having risk factors for MASLD/MASH. Of these, 53 had abnormal Fib-4 scores with no prior work-up; 29 patients consented to a shear wave elastography; 16 underwent shear wave elastography; and 6 had moderate or high results concerning for at-risk fibrosis. Twenty patients attended MASLD-focused appointments. Reluctance to pursue testing was driven by skepticism surrounding preventative medicine, perceived cost, and desire to focus on other medical problems, some of which were life-limiting. CONCLUSION Panel management represents a scalable strategy to quickly identify patients in primary care most likely to experience complications from MASLD/MASH and provides a targeted intervention to direct further management. Limitations include access to care, medical complexity, and patient acceptance.
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Affiliation(s)
- Sarah Householder
- Departments of Internal Medicine and Pediatrics, Yale New Haven Hospital, New Haven, CT, USA
| | - Andrew J Loza
- Department of Emergency Medicine, Yale New Haven Hospital, New Haven, CT, USA
| | - Vikas Gupta
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Benjamin R Doolittle
- Department of Internal Medicine, Internal Medicine and Pediatrics, Yale New Haven Hospital, New Haven, CT, USA
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Yu H, Su X, Tao W, Sun W, Zhang X, Han Q, Zhao Z, Zhang Y, Chen X, Liu X, Jia D, Fang L, Li L. Prevalence and characteristics of liver steatosis and fibrosis in type 2 diabetes mellitus (T2DM) patients: a cross-sectional study in populations of eastern China. BMJ Open 2024; 14:e087550. [PMID: 39672583 PMCID: PMC11647396 DOI: 10.1136/bmjopen-2024-087550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 11/22/2024] [Indexed: 12/15/2024] Open
Abstract
OBJECTIVES To describe the prevalence, clinical characteristics and risk factors of liver steatosis and fibrosis in type 2 diabetes mellitus (T2DM) patients in eastern China. DESIGN A cross-sectional, multicentre study based on an ongoing cohort study. SETTING 16 clinics in eastern China, including primary clinics to tertiary hospitals. PARTICIPANTS 1816 patients with T2DM diagnosis who met the inclusion criteria were recruited into the study. INTERVENTION Participants underwent elastography examination. MAIN OUTCOME MEASURES Descriptive analysis was performed to calculate the prevalence and characteristics of liver steatosis and fibrosis. The correlated factors were analysed using single- and multivariate logistic regression analysis. RESULTS The prevalence of liver steatosis in T2DM patients is 69.7%, with 46% moderate to severe steatosis. 34.6% and 6.7% of the patients were detected with liver fibrosis and cirrhosis. Steatosis patients were younger, had higher body mass index (BMI), higher levels of insulin resistance and more severe lipid metabolism disorders. Similar trends of differences were observed in patients with fibrosis. Female gender (OR=0.574, 95% CI 0.381 to 0.865), BMI (OR=1.491, 95% CI 1.375 to 1.616), disease duration, inflammation and serum lipid profile markers were risk factors of steatosis, while BMI (OR=1.204, 95% CI 1.137 to 1.275) and female gender (OR=0.672, 95% CI 0.470 to 0.961) were still the most significant predictors of liver fibrosis. CONCLUSIONS The prevalence of liver steatosis and fibrosis were high in patients with T2DM. Liver steatosis and fibrosis in these patients appeared to be more associated with lipid metabolism disorders and insulin resistance rather than glucose levels. TRIAL REGISTRATION NUMBER Clinical trial: NCT05597709.
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Affiliation(s)
- Hekai Yu
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Xianghui Su
- Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, Xinjiang, China
| | - Wenxuan Tao
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Weixia Sun
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
- Southeast University, Nanjing, Jiangsu, China
| | - Xiaoyan Zhang
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
| | - Qing Han
- Department of Endocrinology, Southeast University, Nanjing, Jiangsu, China
| | - Zhuoxiao Zhao
- Nanjing Gaochun Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Yan Zhang
- Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xiaoqian Chen
- Department of Endocrinology, Nanjing Central Hospital, Nanjing, Jiangsu, China
| | - Xinliang Liu
- Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China
| | - Dianrong Jia
- Department of Endocrinology, Taizhou Jiangyan Hospital of Traditional Chinese Medicine, Taizhou, Jiangsu, China
| | - Li Fang
- Nanjing Gaochun Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China
| | - Ling Li
- Department of Endocrinology, School of Medicine, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China
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Odanga JJ, Anderson SM, Presnell SC, LeCluyse EL, Chen J, Weaver JR. Impact of Post-Thaw Enrichment of Primary Human Hepatocytes on Steatosis, Inflammation, and Fibrosis in the TruVivo ® System. Pharmaceuticals (Basel) 2024; 17:1624. [PMID: 39770467 PMCID: PMC11728523 DOI: 10.3390/ph17121624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 11/26/2024] [Accepted: 11/27/2024] [Indexed: 01/16/2025] Open
Abstract
Background: Liver diseases are a global health concern. Many in vitro liver models utilize cryopreserved primary human hepatocytes (PHHs), which commonly undergo post-thaw processing through colloidal silica gradients to remove debris and enrich for a viable PHH population. Post-thaw processing effects on healthy PHHs are partially understood, but the consequences of applying disease-origin PHHs to post-thaw density gradient separation have not been described. Methods: Using the TruVivo® system, diseased, type 2 diabetes mellitus (T2DM), and fibrotic PHHs were cultured for 14 days after initially being subjected to either low-density (permissive) or high-density (selective) gradients using Percoll-based thawing medium. Results: Changes in functionality, including albumin and urea secretion and CYP3A4 activity, were measured in diseased, T2DM, and fibrotic PHHs enriched in low Percoll compared to PHHs enriched in high Percoll. Lipogenesis increased in the PHHs enriched in low Percoll. Higher expression of CK18 and TGF-β, two fibrotic markers, and changes in expression of the macrophage markers CD68 and CD163 were also measured. Conclusions: The use of Percoll for the enrichment of PHHs post-thaw results in differences in attachment and functionality, along with changes in diseased phenotypes, in the TruVivo® system.
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Affiliation(s)
- Justin J. Odanga
- Institute of Regenerative Medicine, LifeNet Health, VA Beach, VA 23453, USA; (J.J.O.); (S.M.A.); (S.C.P.); (J.C.)
| | - Sharon M. Anderson
- Institute of Regenerative Medicine, LifeNet Health, VA Beach, VA 23453, USA; (J.J.O.); (S.M.A.); (S.C.P.); (J.C.)
| | - Sharon C. Presnell
- Institute of Regenerative Medicine, LifeNet Health, VA Beach, VA 23453, USA; (J.J.O.); (S.M.A.); (S.C.P.); (J.C.)
| | - Edward L. LeCluyse
- Research and Development, LifeNet Health, Research Triangle Park, NC 27709, USA;
| | - Jingsong Chen
- Institute of Regenerative Medicine, LifeNet Health, VA Beach, VA 23453, USA; (J.J.O.); (S.M.A.); (S.C.P.); (J.C.)
| | - Jessica R. Weaver
- Institute of Regenerative Medicine, LifeNet Health, VA Beach, VA 23453, USA; (J.J.O.); (S.M.A.); (S.C.P.); (J.C.)
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Huang N, Su X, Yu T, Wu X, Lu B, Sun W, Yao L, Wang M, Wang Y, Wu W, Liu Y, Yang T, Gao R, Miao C, Li L. Serum 25-hydroxy vitamin D level is associated with elastography-detected liver fibrosis in patients with type 2 diabetes mellitus in China. Front Endocrinol (Lausanne) 2024; 15:1420088. [PMID: 39698035 PMCID: PMC11653015 DOI: 10.3389/fendo.2024.1420088] [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: 04/19/2024] [Accepted: 10/28/2024] [Indexed: 12/20/2024] Open
Abstract
Objective In this cross-sectional study including patients with type 2 diabetes mellitus (T2DM) we aimed to explore the relationship between serum 25-hydroxy vitamin (25(OH)D) level and liver steatosis and fibrosis in the Chinese population. Methods Patients visiting 16 clinical centers with T2DM were recruited. Their liver steatosis and fibrosis status were then assessed using elastography. Factors associated with steatosis and fibrosis were explored using regression analysis. Correlations between serum 25(OH)D levels and other patient characteristics were analyzed using linear regression. Results In total, 1,513 patients with T2DM were included in the study. The prevalence of steatosis and fibrosis was 69.7%, and 34.6%, separately. A lower level of 25(OH)D was detected in patients with liver steatosis compared to those without, although it was not an independent predictor of this condition. However, 25(OH)D level was independently associated with liver fibrosis even when adjusted for age, sex, body mass index, hemoglobin A1c, insulin, and homeostatic model assessment of insulin resistance (OR = 0.964 [0.935-0.993], P = 0.015). When patients were separated into subgroups by sex, a correlation between 25(OH)D and fibrosis was identified in the male group (OR = 0.969 [0.940-0.998], P = 0.038). Conclusions In conclusion, this multi-center, cross-sectional study in patients with T2DM showed that serum 25-hydroxy vitamin D level was strongly associated with liver fibrosis and this relationship was more pronounced in male patients. Clinical trial registration https://clinicaltrials.gov/ct2/show/, identifier NCT05597709.
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Affiliation(s)
- Nan Huang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Ting Yu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiaodong Wu
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Bing Lu
- Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University, Suzhou, China
| | - Weixia Sun
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
| | - Liqin Yao
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China
| | - Maoyun Wang
- Department of Endocrinology, Baoying Hospital of Traditional Chinese Medicine, Yangzhou, China
| | - Yao Wang
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China
| | - Wenxuan Wu
- Department of Endocrinology, Yixing Hospital of Traditional Chinese Medicine, Yixing, China
| | - Yingzhao Liu
- Department of Endocrinology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China
| | - Ting Yang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Ruidong Gao
- Department of Endocrinology, Baoying Hospital of Traditional Chinese Medicine, Yangzhou, China
| | - Congqing Miao
- Department of Endocrinology, Jiangdu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing, China
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Heyens L, Kenjic H, Dagnelie P, Schalkwijk C, Stehouwer C, Meex S, Kooman J, Bekers O, van Greevenbroek M, Savelberg H, Robaeys G, de Galan B, Koster A, van Dongen M, Eussen S, Koek G. Forns index and fatty liver index, but not FIB-4, are associated with indices of glycaemia, pre-diabetes and type 2 diabetes: analysis of The Maastricht Study. BMJ Open Gastroenterol 2024; 11:e001466. [PMID: 39615896 PMCID: PMC11624825 DOI: 10.1136/bmjgast-2024-001466] [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: 05/30/2024] [Accepted: 10/07/2024] [Indexed: 12/09/2024] Open
Abstract
OBJECTIVE Glucose metabolism status (GMS) is linked to non-alcoholic fatty liver disease (NAFLD). Higher levels of advanced glycation end products (AGEs) are observed in people with type 2 diabetes mellitus (T2DM) and NAFLD. We examined the association between GMS, non-invasive tests and AGEs, with liver steatosis and fibrosis. METHODS Data from The Maastricht Study, a population-based cohort, were analysed. Participants with alcohol overconsumption or missing data were excluded. GMS was determined via an oral glucose tolerance test. AGEs, measured by skin autofluorescence (SAF), were assessed using an AGE Reader. Associations of GMS and SAF with the fibrosis-4 score (FIB-4), Forns index (FI) and fatty liver index (FLI) were investigated using multivariable linear regression, adjusted for sociodemographic, lifestyle and clinical variables. RESULTS 1955 participants (56.6%) were analysed: 598 (30.6%) had T2DM, 264 (13.5%) had pre-diabetes and 1069 (54.7%) had normal glucose metabolism. Pre-diabetes was significantly associated with FLI (standardised regression coefficient (Stβ) 0.396, 95% CI 0.323 to 0.471) and FI (Stβ 0.145, 95% CI 0.059 to 0.232) but not FIB-4. T2DM was significantly associated with FLI (Stβ 0.623, 95% CI 0.552 to 0.694) and FI (Stβ 0.307, 95% CI 0.226 to 0.388) but not FIB-4. SAF was significantly associated with FLI (Stβ 0.083, 95% CI 0.036 to 0.129), FI (Stβ 0.106, 95% CI 0.069 to 0.143) and FIB-4 (Stβ 0.087, 95% CI 0.037 to 0.137). CONCLUSION The study showed that adverse GMS and higher glycaemia are positively associated with steatosis. FI, but not FIB-4, was related to adverse GMS concerning fibrosis. This study is the first to demonstrate that SAF is positively associated with steatosis and fibrosis.
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Affiliation(s)
- Leen Heyens
- Hasselt University Faculty of Medicine and Life Sciences, Diepenbeek, Belgium
- Maastricht University Faculty of Health Medicine and Life Sciences, Maastricht, The Netherlands
| | - Hanna Kenjic
- School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Pieter Dagnelie
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Maastricht University Medical Centre+ Internal Medicine, Maastricht, The Netherlands
| | - Casper Schalkwijk
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Maastricht University Medical Centre+ Internal Medicine, Maastricht, The Netherlands
| | - Coen Stehouwer
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
| | - Steven Meex
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Department Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Jeroen Kooman
- School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
- Maastricht University Medical Centre+ Internal Medicine, Maastricht, The Netherlands
| | - Otto Bekers
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Department Clinical Chemistry, Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Marleen van Greevenbroek
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Maastricht University Medical Centre+ Internal Medicine, Maastricht, The Netherlands
| | - Hans Savelberg
- School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Geert Robaeys
- Hasselt University Faculty of Medicine and Life Sciences, Diepenbeek, Belgium
| | - Bastiaan de Galan
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Department of Social Medicine, Maastricht University, Maastricht, The Netherlands
| | - Annemarie Koster
- Department of Epidemiology, Maastricht University, Maastricht, The Netherlands
- CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands
| | - Martien van Dongen
- CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands
| | - Simone Eussen
- CARIM Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
- Department of Epidemiology, Maastricht University, Maastricht, The Netherlands
| | - Ger Koek
- School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
- Maastricht University Medical Centre+ Internal Medicine, Maastricht, The Netherlands
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La Mura V, Cardinale V, De Cristofaro R, De Santis A, Di Minno G, Fabris L, Marra F, Morisco F, Peyvandi F, Pompili M, Santoro C, Zanon E, Castaman G. Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice. Blood Adv 2024; 8:5725-5734. [PMID: 39226466 PMCID: PMC11599981 DOI: 10.1182/bloodadvances.2024013750] [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: 05/23/2024] [Revised: 08/23/2024] [Accepted: 08/23/2024] [Indexed: 09/05/2024] Open
Abstract
Adeno-associated virus-based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy. To prevent harmful liver-related effects, gene therapy is contraindicated in patients with uncontrolled liver infections, autoimmune hepatitis, liver stiffness ≥8 kPa, or cirrhosis. Before using gene therapy in patients with liver steatosis or other liver disorders, the risk of liver damage should be considered using a highly individualized approach. Treatment is not recommended in patients with abnormal liver enzymes, including alanine aminotransferase (ALT) at any level above the upper limit of normal (ULN). Therefore, pretreatment assessment of liver health should include laboratory tests, abdominal ultrasound, and liver stiffness measurements by transient elastography (TE). In the first year after therapy, ALT levels should be monitored 1 to 2 times per week to detect elevations ≥1.5× ULN, which may require immunosuppressant therapy. Patients with ALT elevation should receive prednisone 60 mg/d for 2 weeks, followed by stepwise tapering when ALT returns to baseline. ALT monitoring should continue long term (every 3-6 months), along with abdominal ultrasound (every 6 months) and TE (yearly) evaluations. When patients with good liver health are selected for treatment and closely monitored thereafter, ALT elevations can be promptly treated and are expected to resolve without long-term hepatic sequelae.
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Affiliation(s)
- Vincenzo La Mura
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Vincenzo Cardinale
- Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Università di Roma, Rome, Italy
| | - Raimondo De Cristofaro
- Servizio Malattie Emorragiche e Trombotiche, Dipartimento di Medicina e Chirurgia Traslazionale, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica S. Cuore Roma, Rome, Italy
| | - Adriano De Santis
- Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Università di Roma, Rome, Italy
| | - Giovanni Di Minno
- Regional Reference Centre for Hemo-Coagulation Diseases, Federico II University, Naples, Italy
| | - Luca Fabris
- Department of Medicine, Clinical Medicine 1, University-Hospital of Padua, Padua, Italy
- Department of Internal Medicine, Digestive Disease Section, Yale Liver Center, Yale University, New Haven, CT
| | - Fabio Marra
- Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Liver and Biliary Diseases Unit, University Federico II, Naples, Italy
| | - Flora Peyvandi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Maurizio Pompili
- UOC Medicina Interna e del Trapianto di Fegato, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del S. Cuore, Rome, Italy
| | - Cristina Santoro
- Department of Hematology, University Hospital Policlinico Umberto I, Rome, Italy
| | - Ezio Zanon
- Hemophilia Centre, Clinical Medicine 1, University Hospital of Padua, Padua, Italy
| | - Giancarlo Castaman
- Center for Bleeding Disorders, Department of Oncology, Careggi University Hospital, Florence, Italy
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Kaylan KB, Paul S. NAFLD No More: A Review of Current Guidelines in the Diagnosis and Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Curr Diab Rep 2024; 25:5. [PMID: 39535566 DOI: 10.1007/s11892-024-01558-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/10/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE OF REVIEW Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation. RECENT FINDINGS Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications. MASLD has been increasing in prevalence and disease burden but is underrecognized in primary care and endocrinology clinics. Multiple society guidelines, synthesized here, provide a framework for the initial approach in the diagnosis and evaluation of MASLD. Recent advances in pharmacologic treatment underline the importance of screening for patients who are at risk for advanced fibrosis as they are most likely to benefit from new drug classes, such as the liver-directed thyroid receptor agonist resmiterom.
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Affiliation(s)
- Kerim B Kaylan
- Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago Medicine, Chicago, IL, USA
| | - Sonali Paul
- Section of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, The University of Chicago Medicine, Chicago, IL, USA.
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ElGhandour AM, Teama NM, Kamal MA, Nashaat EH, Ghani AMA, Abdo AA. Diagnostic and prognostic value of plasma lipocalin-2 levels in patients with metabolic dysfunction–associated steatotic liver disease. EGYPTIAN LIVER JOURNAL 2024; 14:80. [DOI: 10.1186/s43066-024-00387-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 10/27/2024] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
Non-Alcoholic Fatty Liver Disease, recently better recognised as Metabolic Dysfunction–Associated Steatotic Liver Disease, is the most prevalent form of chronic liver disease at present time. It is estimated to impact 32% of the world's population, hence representing a significant health burden.
Aim of the work
To assess the significance of plasma Lipocalin-2 (LCN2) levels in the diagnosis and prognosis of NAFLD patients.
Patients and methods
In this retrospective case–control study we recruited 102 subjects aged between 18 and 70 years. The included participants were split into two study groups. Group I: 51 NAFLD patients (61% men, 39% females) and Group II: 51 healthy controls (51% men and 49% females), for whom plasma LCN2 levels were assessed and correlated with NAFLD fibrosis score, FIB4 and fatty liver index.
Results
In this study, LCN2 levels in NAFLD patients were significantly greater compared to individuals in the control group (p < 0.001), with a mean of 1893.214 ± 1002.852 ng/dL in the cases and a mean of 466.020 ± 397.699 ng/dL in the controls. This suggests the use of LCN2 as a possible diagnostic marker of NAFLD. The mean LCN2 levels in this study also significantly increased as the grade of fatty liver increased from I to III (p < 0.001). This in turn proposes the use of LCN2 as a prognostic marker for NAFLD progression. LCN2 also significantly correlated with the fatty liver index and NAFLD Fibrosis scoring systems, but not with Fib-4. With an area under the ROC of 0.906, it demonstrated excellent diagnostic performance with 84% sensitivity, 90% specificity, 89.6% PPV and 85.2% NPV for the prediction of NAFLD patients.
Conclusion
Lipocalin-2 performs as a diagnostic and a possible prognostic marker for metabolic dysfunction-associated steatotic liver disease.
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Kowada A. Risk-stratified hepatocellular carcinoma screening according to the degree of obesity and progression to cirrhosis for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD) in Japan: a cost-effectiveness study. BMJ Open 2024; 14:e080549. [PMID: 39500609 PMCID: PMC11552604 DOI: 10.1136/bmjopen-2023-080549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 10/14/2024] [Indexed: 11/13/2024] Open
Abstract
OBJECTIVE To evaluate the cost-effectiveness of risk-stratified hepatocellular carcinoma (HCC) screening in diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DESIGN A state-transition model from a healthcare payer perspective on a lifetime horizon. SETTING Japan. POPULATION A hypothetical cohort of 50-year-old diabetic patients with MASLD risk-stratified according to degree of obesity and progression to cirrhosis. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis (MASH) and MASH cirrhosis are progressive manifestations of this specific type of liver disease. INTERVENTION Abdominal ultrasound (US), US with alpha-fetoprotein (AFP), US with AFP and lectin-reactive alpha-fetoprotein (AFP-L3), CT, extracellular contrast-media-enhanced MRI (ECCM-MRI), gadoxetic acid-enhanced MRI (EOB-MRI) and no screening. MAIN OUTCOME MEASURE Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), early-stage HCC cases, advanced-stage HCC cases and HCC-related deaths. RESULTS EOB-MRI is the most cost-effective screening method for non-obese diabetic patients with MASH cirrhosis and for obese diabetic patients with MASH and MASH cirrhosis. Cost-effectiveness was sensitive to HCC incidence in non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH, and the adherence rate of HCC screening in obese diabetic patients with MASH. When the semiannual HCC incidence was between 0.008 and 0.0138 in non-obese diabetic patients with MASH cirrhosis, US with AFP was more cost-effective than EOB-MRI. Cost-effectiveness acceptability curves showed that EOB-MRI was 50.7%, 96.0% and 99.9% cost-effective in obese diabetic patients with MASH and non-obese diabetic patients with MASH cirrhosis, and obese diabetic patients with MASH cirrhosis at a willingness-to-pay level of $50 000 per QALY gained. Compared with no screening in 100 000 non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH cirrhosis, EOB-MRI reduced total costs by US$69 million and by US$142 million, increased lifetime effectiveness by 12 546 QALYs and by 15 815 QALYs, detected 17 873 and 21 014 early-stage HCC cases, and averted 2068 and 2471 HCC-related deaths, respectively. CONCLUSIONS Of all HCC screening methods for diabetic patients with MASH cirrhosis, EOB-MRI yields the greatest cost-saving with the highest QALYs, detects the greatest number of early-stage HCC cases and averts the greatest number of advanced-stage HCC cases and HCC-related deaths. The findings provide important insights for the precise implementation of risk-stratified HCC surveillance to reduce morbidity and mortality and improve the quality of life in diabetic patients with MASLD.
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Affiliation(s)
- Akiko Kowada
- Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan
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Inukai Y, Ito T, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Honda T, Shimizu T, Hattori M, Takeyama T, Ando Y, Nishikawa T, Morita K, Toyoda H, Ishigami M, Kawashima H. Type 2 Diabetes and Hypertension as Risk Factors for Advanced Fibrosis in Biopsy Proven Metabolic Dysfunction-Associated Steatotic Liver Disease. J Dig Dis 2024; 25:685-693. [PMID: 39805320 DOI: 10.1111/1751-2980.13325] [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: 05/27/2024] [Revised: 12/04/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025]
Abstract
OBJECTIVES To identify the diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) related to liver fibrosis and to characterize patients with cryptogenic steatotic liver disease (SLD) (non-MASLD) among those previously diagnosed with nonalcoholic fatty liver disease (NAFLD). METHODS This multicenter retrospective study included 511 patients diagnosed with NAFLD via liver biopsy, and the prevalence of MASLD was assessed based on the diagnostic criteria. Patients were divided into those who met the MASLD criteria and those who did not, and the characteristics of advanced fibrosis and associated cardiometabolic factors were evaluated. RESULTS Of the 475 patients with NAFLD, 458 (96.4%) met the criteria for MASLD, showing a high overlap between classical NAFLD and MASLD populations. Severe fibrosis was observed, regardless of the number of cardiometabolic factors. Hypertension and diabetes mellitus significantly contributed to advanced fibrosis (≥ F3), with odds ratio of 1.92 and 2.00 (95% confidence interval of 1.17-3.16 and 1.22-3.28, respectively; both p < 0.01) on multivariate analysis. The other seventeen (3.6%) patients did not meet the diagnostic criteria for MASLD. Among them, seven had significant fibrosis and a high fibrosis-4 index. CONCLUSIONS Diabetes mellitus and hypertension are key metabolic factors associated with advanced fibrosis. Some cases, classified as cryptogenic SLD, also exhibit significant fibrosis. Consequently, identifying high-risk patients, including those undergoing noninvasive tests for fibrosis, is crucial.
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Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinya Yokoyama
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tatsuji Shimizu
- Department of Gastroenterology, Japan Community Health Care Organization Kani Tono Hospital, Kani, Japan
| | - Masashi Hattori
- Department of Gastroenterology, Yamashita Hospital, Ichinomiya, Japan
| | - Tomoaki Takeyama
- Department of Gastroenterology, Nishichita General Hospital, Tokai, Japan
| | - Yusuke Ando
- Department of Gastroenterology, Handa City Hospital, Handa, Japan
| | | | - Kiyoshi Morita
- Department of Gastroenterology, Toyota Kosei Hospital, Toyota, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Martínez-Sánchez FD, Medina-Julio D, Córdova-Gallardo J, Corredor-Nassar MJ, Méndez-Sánchez N. Type 2 Diabetes Subtypes and Their Role in Metabolic Liver Disease and Fibrosis Progression. Med Sci Monit 2024; 30:e946016. [PMID: 39449183 PMCID: PMC11520462 DOI: 10.12659/msm.946016] [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: 07/30/2024] [Accepted: 09/09/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND The relationship between different subgroups of type 2 diabetes (T2D) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis has not been thoroughly studied. This study aims to determine the association between T2D subgroups and the risk of developing advanced liver fibrosis using the Fibrosis-4 (FIB-4) index, a non-invasive marker for assessing liver fibrosis risk. MATERIAL AND METHODS A total of 1205 patients with T2D were categorized into 4 distinct subgroups: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). The FIB-4 index was calculated for each patient to estimate the degree of liver fibrosis, with the following cutoff points: <1.3 indicating no or mild fibrosis, 1.3-2.67 suggesting moderate fibrosis, and >2.67 indicating advanced fibrosis (F3-F4). Logistic regression was used to compare the odds of advanced fibrosis across these subgroups. RESULTS The SIRD subgroup exhibited significantly higher odds of advanced liver fibrosis (F3-F4), compared with the other subgroups, as indicated by elevated FIB-4 scores (P<0.05). In contrast, the SIDD and MOD subgroups had lower odds of advanced fibrosis, while the MARD subgroup showed an intermediate association. CONCLUSIONS The findings suggest that the FIB-4 index, as a noninvasive assessment tool, effectively stratifies liver fibrosis risk among different T2D subgroups. This stratification can inform more personalized management strategies for patients with MASLD, underscoring the importance of accounting for the heterogeneity within T2D in clinical assessments of liver fibrosis risk.
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Affiliation(s)
- Froylan David Martínez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Copilco University, Mexico City, Mexico
- Department of Internal Medicine, Hospital General “Dr. Manuel Gea González”, Mexico City, Mexico
| | - David Medina-Julio
- Faculty of Medicine, National Autonomous University of Mexico, Copilco University, Mexico City, Mexico
- Department of Internal Medicine, Hospital General “Dr. Manuel Gea González”, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Faculty of Medicine, National Autonomous University of Mexico, Copilco University, Mexico City, Mexico
- Department of Hepatology, Hospital General “Dr. Manuel Gea González”, Mexico City, Mexico
| | | | - Nahum Méndez-Sánchez
- Faculty of Medicine, National Autonomous University of Mexico, Copilco University, Mexico City, Mexico
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
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Lin Y, Liang Z, Liu X, Chong Y. Association between changes in body composition and progression of liver fibrosis in patients with type 2 diabetes mellitus. Front Nutr 2024; 11:1476467. [PMID: 39498408 PMCID: PMC11532110 DOI: 10.3389/fnut.2024.1476467] [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: 08/05/2024] [Accepted: 10/07/2024] [Indexed: 11/07/2024] Open
Abstract
Aim The correlation between type 2 diabetes mellitus (T2DM) and the occurrence of liver fibrosis is well-established. However, the longitudinal association between body composition and liver fibrosis progression in patients with T2DM remains incompletely explored. Methods Total of 390 patients with T2DM underwent body composition assessments, followed by a median duration of 2.13 years. The calculated parameters included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F) and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). Liver fibrosis was evaluated through liver stiffness measurement (LSM). Patients were classified according to BMI and body composition, followed by a comprehensive investigation into the impact of body composition changes on liver fibrosis outcomes. Results Among 72 patients with incident advanced liver fibrosis at readmission, ΔBMI, ΔFMI and ΔTFMI increased, while ΔM/F and ΔA/T decreased. Individuals who kept obese had a dramatically elevated hazard of incident advanced liver fibrosis compared to those who kept non-obese, with an adjusted odds ratio of 3.464. When TFMI heightened, the hazard of incident advanced liver fibrosis was 3.601 times higher compared to the decreased group. Additionally, individuals in increased ASMI and A/T groups showed a slight advantage in preventing incident advanced liver fibrosis compared to the stable groups. Conclusion Stable obesity was associated with a greater hazard of liver fibrosis advancement, and an increase in TFMI may promote the progression of liver fibrosis. Maintaining a balanced muscle/fat ratio appeared to help prevent the progression.
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Affiliation(s)
- Yuxi Lin
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhixing Liang
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaofang Liu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yutian Chong
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Álvares-da-Silva MR, Vargas MDS, Rabie SMS, Jonko G, Riedel PG, Longo L, Gonçalves MR, Luft VC, Joveleviths D. FLI and FIB-4 in diagnosing metabolic dysfunction-associated steatotic liver disease in primary care: High prevalence and risk of significant disease. Ann Hepatol 2024; 30:101584. [PMID: 39395769 DOI: 10.1016/j.aohep.2024.101584] [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: 01/21/2024] [Revised: 08/22/2024] [Accepted: 08/30/2024] [Indexed: 10/14/2024]
Abstract
INTRODUCTION AND OBJECTIVES Public health policies in metabolic dysfunction-associated steatotic liver disease (MASLD) are still lacking. This study aims to estimate the prevalence and severity of MASLD in primary health care (PHC) through non-invasive markers. PATIENTS AND METHODS Two-phase study, including a retrospective (RETR) and a prospective (PROS) one, was carried out in PHC in Brazil. In RETR, metabolic and hepatic profiles of 12,054 patients, including FIB-4, were evaluated. In PROS, 350 patients were randomly selected and submitted to a clinical and nutritional assessment. RESULTS RETR (65.4 % women, mean age 55.3 years old): dyslipidemia, hypertension, and type 2 diabetes mellitus (T2DM) present in 40.8 %, 34.3 %, and 12.2 % of the electronic health records, respectively. Fasting glucose >100 mg/dL in 34.5 %, and glycated hemoglobin higher than 5.7 % in 51.5 %, total cholesterol >200 mg/dL and triglycerides >150 mg/dL in 40.8 % and 32.1 %, respectively. Median FIB-4 was of 1.33, 5 % >2.67. No one had MASLD as a diagnostic hypothesis; PROS (71.8 % women, mean age 58 years old): body mass index (BMI) ≥30 kg/m² in 31.8 %. MASLD prevalence (FLI≥ 30 + cardiometabolic features) of 62.1 %; 39.4 % of patients had FLI ≥60, with higher BMI, waist circumference, fasting glucose, triglycerides, AST, ALT and GGT, as well as lower HDL-cholesterol (p < 0.001). FIB-4>1.3 in 40 % and NAFLD Fibrosis Score (NFS)>-1.45 in 59.2 % of steatotic patients. CONCLUSIONS There is a high prevalence of MASLD in PHC, with a significant risk of liver fibrosis. These findings reinforce we need to develop public policies to defeat MASLD epidemics.
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Affiliation(s)
- Mário Reis Álvares-da-Silva
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Experimental Laboratory in Hepatology and Gastroenterology, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Gastroenterology and Hepatology Unit, HCPA, Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Department of Internal Medicine, UFRGS, Porto Alegre, 91501-970, Rio Grande do Sul, Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq Researcher, Brasília 71.605-001, Distrito Federal, Brazil.
| | - Márcia da Silva Vargas
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Nutrition Unit, HCPA, Porto Alegre, 90035-007, Rio Grande do Sul, Brazil
| | - Soheyla Mohd Souza Rabie
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Nutrition Unit, HCPA, Porto Alegre, 90035-007, Rio Grande do Sul, Brazil
| | - Gabriella Jonko
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil
| | - Patricia Gabriela Riedel
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil
| | - Larisse Longo
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Experimental Laboratory in Hepatology and Gastroenterology, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil
| | - Marcelo Rodrigues Gonçalves
- Department of Social Medicine, UFRGS, Porto Alegre, 90035-003, Rio Grande do Sul, Brazil; Department of Nutrition, School of Medicine, UFRGS, Porto Alegre, 90050-170, Rio Grande do Sul, Brazil; Graduate Program in Food, Nutrition and Health, School of Medicine, UFRGS, Porto Alegre, 90035-007, Rio Grande do Sul, Brazil
| | - Vivian Cristine Luft
- Department of Social Medicine, UFRGS, Porto Alegre, 90035-003, Rio Grande do Sul, Brazil; Department of Nutrition, School of Medicine, UFRGS, Porto Alegre, 90050-170, Rio Grande do Sul, Brazil; Graduate Program in Epidemiology, School of Medicine, UFRGS, Porto Alegre, 90035-003, Rio Grande do Sul, Brazil
| | - Dvora Joveleviths
- Graduate Program in Gastroenterology and Hepatology, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Experimental Laboratory in Hepatology and Gastroenterology, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, 90035-007, Rio Grande do Sul, Brazil; Department of Social Medicine, UFRGS, Porto Alegre, 90035-003, Rio Grande do Sul, Brazil
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Sharma A, Godina Leiva E, Kalavalapalli S, Lomonaco R, Marangi SA, Valdez Saenz E, Gonzalez MA, Ortiz Rocha A, Cuervo Pardo N, Rosenberg J, Bedossa P, Bril F, Barb D, Cusi K. Obesity increases the risk of hepatic fibrosis in young adults with type 2 diabetes mellitus: the need to screen. Obesity (Silver Spring) 2024; 32:1967-1974. [PMID: 39315409 DOI: 10.1002/oby.24130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/18/2024] [Accepted: 07/03/2024] [Indexed: 09/25/2024]
Abstract
OBJECTIVE The objective of this study was to determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in young compared with older adults. METHODS Individuals (n = 1420) with (63%) and without type 2 diabetes mellitus (T2D; 37%) who attended internal medicine clinics and did not have a known history of MASLD underwent laboratory evaluation and transient elastography to assess for hepatic steatosis and fibrosis. Magnetic resonance elastography and liver biopsy were recommended when indicated. RESULTS A total of 243 participants were ages <45 years, and 1177 were ages ≥45 years. Obesity, T2D, and metabolic syndrome were highly prevalent in young adults. Frequencies of steatosis and fibrosis were high in young adults (50.2% and 7.5% vs. older adults 52.7% and 9.9%, respectively) and were significantly higher in those with both obesity and T2D (71.1% and 15.7%, respectively; p < 0.01). In young adults, T2D and obesity were the strongest risk factors for hepatic fibrosis (odds ratios 4.33 [95% CI: 1.37-13.68] and 1.16 [95% CI: 1.07-1.25], respectively; p < 0.05). CONCLUSIONS There is a high prevalence of clinically significant hepatic fibrosis in young adults with cardiometabolic risk factors. Up to one in seven young adults with obesity and T2D had clinically significant hepatic fibrosis on elastography. This highlights the need to screen young adults with cardiometabolic risk factors for MASLD for early detection and intervention.
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Affiliation(s)
- Anu Sharma
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Eddison Godina Leiva
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Srilaxmi Kalavalapalli
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Stephen A Marangi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Enrique Valdez Saenz
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Maria A Gonzalez
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Andrea Ortiz Rocha
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Nathaly Cuervo Pardo
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Jens Rosenberg
- Advanced Magnetic Resonance Imaging and Spectroscopy Facility, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
| | - Pierre Bedossa
- Department of Pathology, Hôpital Beaujon AP-HP, Clichy, France
| | - Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Diana Barb
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida College of Medicine, Gainesville, Florida, USA
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Younossi ZM, Golabi P, Price JK, Owrangi S, Gundu-Rao N, Satchi R, Paik JM. The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes. Clin Gastroenterol Hepatol 2024; 22:1999-2010.e8. [PMID: 38521116 DOI: 10.1016/j.cgh.2024.03.006] [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: 12/08/2023] [Revised: 03/01/2024] [Accepted: 03/05/2024] [Indexed: 03/25/2024]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction associated steatotic liver disease (MASLD), is closely associated with type 2 diabetes (T2D). Our aim was to estimate the most recent global prevalence of NAFLD/MASLD, nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction associated steatohepatitis (MASH), advanced fibrosis, and mortality among patients with T2D. METHODS We systematically searched PubMed and Ovid MEDLINE for terms including NAFLD, NASH, and T2D published in 1990-2023 according to PRISMA. The meta-analysis was conducted using a random-effects model. Assessment of bias risk used the Joanna Briggs Institute appraisal tool. RESULTS From 3134 studies included in the initial search, 123 studies (N = 2,224,144 patients with T2D) were eligible. Another 12 studies (N = 2733 T2D patients with liver biopsy) were eligible for histologic assessments. The global pooled prevalence of NAFLD/MASLD among patients with T2D was 65.33% (95% confidence interval, 62.35%-68.18%). This prevalence increased from 55.86% (42.38%-68.53%) in 1990-2004 to 68.81% (63.41%-73.74%) in 2016-2021 (P = .073). The highest NAFLD/MASLD prevalence among T2D patients was observed in Eastern Europe (80.62%, 75.72%-84.73%), followed by the Middle East (71.24%, 62.22%-78.84%), and was lowest in Africa (53.10%, 26.05%-78.44%). Among patients with liver biopsy data, the global pooled prevalence of NASH/MASH, significant fibrosis, and advanced fibrosis was 66.44% (56.61%-75.02%), 40.78% (24.24%-59.70%), and 15.49% (6.99%-30.99%), respectively. The pooled all-cause mortality was 16.79 per 1000 person-years (PY) (10.64-26.40), 4.19 per 1000 PY (1.34-7.05) for cardiac-specific mortality; 6.10 per 1000 PY (0.78-4.88) for extrahepatic cancer-specific mortality; and 2.15 per 1000 PY (0.00-2.21) for liver-specific mortality. CONCLUSIONS The prevalence of NAFLD/MASLD among T2D is high and growing. The majority of NAFLD/MASLD patients with T2D have NASH/MASH, and a significant proportion have advanced fibrosis.
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Affiliation(s)
- Zobair M Younossi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; The Global NASH Council, Washington, District of Columbia.
| | - Pegah Golabi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; The Global NASH Council, Washington, District of Columbia
| | - Jillian Kallman Price
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia
| | - Soroor Owrangi
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia
| | | | - Romona Satchi
- The Global NASH Council, Washington, District of Columbia
| | - James M Paik
- Beatty Liver and Obesity Research Program, Inova Health System, Falls Church, Virginia; Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, Virginia; The Global NASH Council, Washington, District of Columbia
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Leith D, Lin YY, Brennan P. Metabolic Dysfunction-associated Steatotic Liver Disease and Type 2 Diabetes: A Deadly Synergy. TOUCHREVIEWS IN ENDOCRINOLOGY 2024; 20:5-9. [PMID: 39526052 PMCID: PMC11548366 DOI: 10.17925/ee.2024.20.2.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 01/11/2024] [Indexed: 11/16/2024]
Abstract
Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) are both facets of the metabolic syndrome, associated with obesity and insulin resistance. MASLD, a term that replaces non-alcoholic fatty liver disease (NAFLD), occurs in up to 70% of people with T2D. Not only do T2D and MASLD commonly co-occur, but there is a synergistic, bidirectional relationship between these conditions, meaning that each affects the natural disease course of the other. As such, it is important for those caring for people with T2D to recognize the importance of this co-diagnosis. In this summary, we detail the synergistic relationship between T2D and MASLD, explain the current challenges in recognizing this common co-diagnosis and suggest practical approaches for those caring for people with T2D to improve the diagnosis and treatment of MASLD.
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Affiliation(s)
- Damien Leith
- Clinical Research Centre, Ninewells Hospital, Dundee, UK
| | - Yeun Yi Lin
- Clinical Research Centre, Ninewells Hospital, Dundee, UK
| | - Paul Brennan
- Clinical Research Centre, Ninewells Hospital, Dundee, UK
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Cheng Y, Hsieh T, Wang C, Kao J. Overlapping group between non-alcoholic fatty liver disease and metabolic associated fatty liver disease better for liver research. JGH Open 2024; 8:JGH370039. [PMID: 39403113 PMCID: PMC11471878 DOI: 10.1002/jgh3.70039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 06/26/2024] [Accepted: 09/23/2024] [Indexed: 01/03/2025]
Abstract
AIMS Metabolic associated fatty liver disease (MAFLD) was proposed to replace "non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria." The group meeting these two diagnostic criteria is called "Overlapping Fatty Liver Disease (FLD)." Its clinical characteristics remain unknown. METHODS This study included participants from the Taiwan Bio-Bank database, where NAFLD was defined as hepatic steatosis in liver ultrasound, with exclusion of other known chronic liver diseases. MAFLD was defined as the presence of hepatic steatosis plus metabolic dysfunction, defined as having any of following three criteria: overweight/obesity, type 2 diabetes mellitus (DM), or ≥2 metabolic risk abnormalities in lean/normal weight subjects. According to these two diagnostic criteria, three groups were identified: "overlapping FLD", "NAFLD alone", and "MAFLD alone." NAFLD fibrosis score (NFS) >0.675 was defined as advanced liver fibrosis. RESULTS Eight thousand thirty-eight NAFLD participants (age 55.86 ± 10.12; males 41.07%) were included in the final analysis. Of them, "overlapping FLD" was diagnosed in 7377 (91.8%) and "NAFLD alone" in 661 (8.2%) participants. "Overlapping FLD" patients were older and had a higher percentage of male, worse metabolic profiles, higher NFS, and the percentage of carotid plaques was higher than those with "NAFLD alone." Multivariate analysis showed age, hypertension, DM, and BMI were positively associated with advanced liver fibrosis in "overlapping FLD" patients. CONCLUSIONS "Overlapping FLD" is better for liver research due to identifying a high-risk population among NAFLD patients. NAFLD definition introduces the heterogeneity through "NAFLD alone" group and MAFLD criteria overcome this limitation.
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Affiliation(s)
- Yu‐Ming Cheng
- Department of Gastroenterology and HepatologyTung's Taichung MetroHarbor HospitalTaichung CityTaiwan
| | - Tsung‐Han Hsieh
- Department of ResearchTaipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationTaipeiTaiwan
| | - Chia‐Chi Wang
- Department of GastroenterologyTaipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi UniversityHualienTaiwan
| | - Jia‐Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of MedicineTaipeiTaiwan
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Gracen L, Aikebuse M, Sarraf B, McPhail SM, Russell AW, O'Beirne J, Irvine KM, Williams S, Valery PC, Powell EE. An Australian Community-Based Metabolic Dysfunction-Associated Steatotic Liver Disease Care Pathway for People with Type 2 Diabetes: Barriers and Considerations. Patient Prefer Adherence 2024; 18:1845-1855. [PMID: 39280346 PMCID: PMC11397175 DOI: 10.2147/ppa.s468705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/13/2024] [Indexed: 09/18/2024] Open
Abstract
Background Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear. Methods Sequential adults with T2D attending selected community clinics during 2021-2023 were invited to receive a "liver health check" (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. "Template" letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants' GPs. Results Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥8), 15 participants with 'red flags' (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the "template" letters favourably on a Likert rating scale. Conclusion The low rate of participation in the "liver health check" and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.
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Affiliation(s)
- Lucy Gracen
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Herston, QLD, Australia
| | - Melanie Aikebuse
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
- Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia
| | - Babak Sarraf
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
- Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Steven M McPhail
- Australian Centre for Health Services Innovation School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia
| | - Anthony W Russell
- Endocrinology and Diabetes, the Alfred Hospital, Melbourne, VIC, Australia
| | - James O'Beirne
- Department of Gastroenterology and Hepatology, Sunshine Coast University Hospital, Birtinya, QLD, Australia
| | - Katharine M Irvine
- Mater Research, Translational Research Institute, Brisbane, QLD, Australia
| | | | | | - Elizabeth E Powell
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
- Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia
- QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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Ismail MH, Al Argan R, Elamin Y, Makki M, Alsheekh L, Alelyani J, Hadhiah Z, Aljidhr Z, Alkhatam N, Alfaddagh H, Alanazi A, Alqahtani S. Automated Fibrosis-4 Index: Simplifying Non-Alcoholic Fatty Liver Disease for Diabetologists. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1278. [PMID: 39202559 PMCID: PMC11356356 DOI: 10.3390/medicina60081278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Patients with type 2 diabetes (T2D) have a high prevalence of non-alcoholic fatty liver disease (NAFLD) (55%) and are at increased risk for developing non-alcoholic steatohepatitis, a severe form of NAFLD. Early detection of advanced fibrosis in patients with T2D and NAFLD is crucial and can prevent progression to chronic liver disease, cirrhosis, and hepatocellular carcinoma. However, screening for liver disease and risk-stratification pathways are not established in patients with T2D. We evaluated the efficacy of using the automated fibrosis-4 (FIB-4) index in routine clinical settings to identify patients requiring further specialist evaluation. Materials and Methods: In this prospective cohort study, individuals diagnosed with T2D were recruited from diabetes clinics at a tertiary university hospital. Demographic, clinical, and laboratory data were comprehensively collected. The FIB-4 index was automatically calculated and integrated into the hospital's electronic medical records (EMRs), which were then stratified by age. Patients with advanced fibrosis (FIB-4 index ≥ 1.3) were referred to a specialist. Student's t-test or the Mann-Whitney U test was used to analyze variables associated with advanced fibrosis. Logistic regression was used to identify predictors of advanced fibrosis. Results: Among the 318 patients with T2D, 9.7% had advanced fibrosis. The majority were females (54.7%) and Saudi nationals (89.6%). Several factors, including age, platelet count, total bilirubin, serum albumin, total cholesterol, low-density lipoprotein, transaminases, and gamma-glutamyl transferase (GGT), showed significant associations with advanced fibrosis (all p < 0.05). Older age, elevated total bilirubin and GGT levels, and prolonged international normalized ratio emerged as independent predictors of advanced fibrosis. Conclusions: Integrating the FIB-4 index into the EMR during the routine care of patients with T2D proved to be a valuable tool in effectively identifying individuals at risk of advanced fibrosis. Our findings emphasize the need for further research to refine screening strategies in this high-risk population.
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Affiliation(s)
- Mona H. Ismail
- Division of Gastroenterology, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (M.M.); (L.A.); (J.A.); (Z.A.); (H.A.)
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (R.A.A.); (Y.E.); (A.A.); (S.A.)
| | - Reem Al Argan
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (R.A.A.); (Y.E.); (A.A.); (S.A.)
- Division of Endocrine, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (Z.H.); (N.A.)
| | - Yasir Elamin
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (R.A.A.); (Y.E.); (A.A.); (S.A.)
- Division of Endocrine, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (Z.H.); (N.A.)
| | - Murtaga Makki
- Division of Gastroenterology, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (M.M.); (L.A.); (J.A.); (Z.A.); (H.A.)
| | - Lameya Alsheekh
- Division of Gastroenterology, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (M.M.); (L.A.); (J.A.); (Z.A.); (H.A.)
| | - Jaber Alelyani
- Division of Gastroenterology, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (M.M.); (L.A.); (J.A.); (Z.A.); (H.A.)
| | - Zahra Hadhiah
- Division of Endocrine, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (Z.H.); (N.A.)
| | - Zahrah Aljidhr
- Division of Gastroenterology, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (M.M.); (L.A.); (J.A.); (Z.A.); (H.A.)
| | - Nazih Alkhatam
- Division of Endocrine, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (Z.H.); (N.A.)
| | - Hind Alfaddagh
- Division of Gastroenterology, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (M.M.); (L.A.); (J.A.); (Z.A.); (H.A.)
| | - Alanoud Alanazi
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (R.A.A.); (Y.E.); (A.A.); (S.A.)
- Division of Endocrine, Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia; (Z.H.); (N.A.)
| | - Shaya Alqahtani
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia; (R.A.A.); (Y.E.); (A.A.); (S.A.)
- Department of Internal Medicine, King Fahd Hospital of the University, Al-Khobar 31952, Saudi Arabia
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Suwała S, Junik R. Assessment of the Liver Steatosis and Fibrosis Risk in Metabolic Syndrome and Its Individual Components, Considering the Varying Definitions Used in Clinical Practice throughout Time: A Retrospective Cross-Sectional Study. Biomedicines 2024; 12:1739. [PMID: 39200204 PMCID: PMC11351204 DOI: 10.3390/biomedicines12081739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/02/2024] Open
Abstract
Multiple modifications of metabolic syndrome diagnostic criteria have been made-NCEP: ATP III (from 2001, modified in 2004), IDF (2005), IDF Consortium (2009), or Polish Scientific Society Consortium standards (2022) are now frequently in use. Hepatosteatosis and hepatofibrosis are commonly mentioned aspects of metabolic syndrome that greatly increase the likelihood of developing complications. The objective of the study was to assess different diagnostic criteria for metabolic syndrome based on the prevalence of liver steatosis and fibrosis. A retrospective analysis was conducted on the medical data of 2102 patients. Out of all the single criteria, meeting the obesity criterion based on waist circumference showed the highest increase in the risk of hepatosteatosis (by 64-69%, depending on the definition used)-hypertriglyceridemia increased the risk of hepatofibrosis by 71%. Regardless of the specific criteria used, patients with metabolic syndrome had a 34-36% increased likelihood of developing hepatosteatosis-the probability of hepatofibrosis varied between 42% and 47% for the criteria established in 2004, 2005, and 2009, while the Polish 2022 criteria were not statistically significant (p = 0.818). It seems appropriate to establish consistent metabolic syndrome diagnostic criteria-the 2009 IDF guidelines are the most effective in assessing hepatosteatosis and fibrosis risk.
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Affiliation(s)
- Szymon Suwała
- Department of Endocrinology and Diabetology, Nicolaus Copernicus University, Collegium Medicum, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;
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