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Chang KC, Su TH, Wu CK, Huang SC, Tseng TC, Hong CM, Hsu SJ, Liu CH, Yang HC, Liu CJ, Kao JH. Metabolic dysfunction-associated steatotic liver disease is associated with increased risks of heart failure. Eur J Heart Fail 2025; 27:512-520. [PMID: 39777761 DOI: 10.1002/ejhf.3567] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 12/06/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
AIMS Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by steatotic liver disease (SLD) and cardiometabolic factors, is increasing in prevalence, but its association with heart failure (HF) is unclear. METHODS AND RESULTS Patients with SLD without a history of HF from 2006 to 2021 were retrospectively included and were classified into MASLD and non-MASLD groups that were followed longitudinally. The primary outcome was the new development of HF, which was sub-classified by echocardiography. Multivariable and propensity score matching analyses were conducted to adjust for confounding factors. Overall, 26 676 patients with SLD were included, with a median age of 51 years and 71% classified as MASLD. During a median follow-up of 6 years, 429 (1.61%) patients developed HF, and 76% were HF with preserved ejection fraction (HFpEF). The risk of HF was significantly higher in patients with MASLD than in those without (sub-distribution hazard ratio [SHR] 2.59, 95% confidence interval [CI] 1.84-3.64) after adjustment of competing mortality. There was a dose-dependent increase in HF risks in patients with more cardiometabolic risk factors (SHR 1.12, 95% CI 1.04-1.22). MASLD was also associated with higher risk of HF-related hospitalization (SHR 2.30, 95% CI 1.31-4.04) and specifically, the risk of HFpEF (SHR 1.91, 95% CI 1.27-2.86). In propensity score-matched cohorts, MASLD was also associated with a 2.52-fold higher risk of HF. CONCLUSION In patients with SLD, those with MASLD show a higher risk of HF, specifically HFpEF. Future studies are warranted to validate the association between HF and MASLD.
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Affiliation(s)
- Kai-Chun Chang
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cho-Kai Wu
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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Huang SC, Su TH, Tseng TC, Liao SH, Hsu SJ, Hong CM, Lan TY, Liu CH, Yang HC, Liu CJ, Kao JH. Pre-Existing and New-Onset Metabolic Dysfunctions Increase Cirrhosis and Its Complication Risks in Chronic Hepatitis B. Am J Gastroenterol 2025; 120:401-409. [PMID: 38920306 DOI: 10.14309/ajg.0000000000002915] [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: 01/22/2024] [Accepted: 06/17/2024] [Indexed: 06/27/2024]
Abstract
INTRODUCTION The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing among the chronic hepatitis B (CHB) population. This study aimed to explore the impact of metabolic dysfunction (MD) on cirrhosis and cirrhotic complication risks in CHB. METHODS Patients with CHB were consecutively recruited between 2006 and 2021. The presence of MD was based on the 5 cardiometabolic criteria specified in the MASLD definition. Patients were categorized into MD/non-MD groups based on these criteria. RESULTS Eleven thousand five hundred two treatment-naive noncirrhotic patients with CHB were included with a median follow-up of 5.3 years. Patients in the MD group (n = 7,314) were older and had lower hepatitis B virus DNA levels than non-MD patients (n = 4,188). After adjustment for clinical and viral factors, MD patients had significantly higher risks of cirrhosis (adjusted hazard ratio [aHR]: 1.82, 95% confidence interval [CI]: 1.40-2.37, P < 0.001) and cirrhotic complications (aHR: 1.30 per MD, 95% CI: 1.03-1.63, P = 0.025) in a dose-dependent manner. Furthermore, new-onset diabetes mellitus during the follow-up aggravated the risk of cirrhotic complications (aHR: 2.87, 95% CI: 1.34-6.11, P = 0.006). Hepatic steatosis was associated with lower risks of cirrhosis (aHR: 0.57 within 5 years, 95% CI: 0.44-0.74, P < 0.001) and cirrhotic complications (aHR: 0.45, 95% CI 0.23-0.88, P = 0.020). Among individuals with hepatic steatosis, patients with MASLD exhibited a higher cirrhosis risk than non-MD patients. DISCUSSION Concurrent and new-onset MDs increase the risks of cirrhosis and cirrhotic complications in patients with CHB, independent of hepatic steatosis. Proactively investigating metabolic comorbidities in CHB is critical to stratify the risk of liver disease progression.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Huang SC, Su TH, Tseng TC, Hsu SJ, Hong CM, Lan TY, Liu CH, Yang HC, Liu CJ, Kao JH. All-cause and cause-specific mortality in patients with chronic hepatitis B and concurrent steatotic liver disease. J Hepatol 2024:S0168-8278(24)02763-6. [PMID: 39675434 DOI: 10.1016/j.jhep.2024.12.009] [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: 07/14/2024] [Revised: 11/15/2024] [Accepted: 12/03/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND & AIMS Steatotic liver disease (SLD) is prevalent among patients with chronic hepatitis B (CHB). However, the effects of metabolic dysfunction-associated SLD (MASLD) on the long-term survival of such patients remain unknown. Accordingly, this study investigated the mortality risks in patients with CHB and concurrent SLD. METHODS Consecutive patients with CHB and concurrent SLD were retrospectively recruited at National Taiwan University Hospital. MASLD was defined by the presence of cardiometabolic risk factors. The cumulative incidences of all-cause and cause-specific mortality were compared. RESULTS A total of 8,718 patients with CHB and concurrent SLD were included from 2006 to 2021. At baseline, the MASLD group (n = 6,562) was older and had a lower proportion of HBeAg positivity and lower HBV DNA levels compared with the non-MASLD group (n = 2,156). After a median follow-up period of 9.1 years, the MASLD group exhibited a higher risk of all-cause mortality compared with the non-MASLD group (adjusted hazard ratio 1.79, 95% CI 1.24-2.58, p = 0.002). Furthermore, cumulative cardiometabolic risk factors dose-dependently elevated the risks of all-cause, liver-related, and cardiovascular mortality (all p <0.05). During the follow-up period, new-onset diabetes mellitus, hypertension, and significant weight gain further increased the risks of all-cause and liver-related mortality (all p <0.05). However, patients with SLD had a lower mortality risk than those without SLD after propensity score matching (hazard ratio 0.62, 95% CI 0.53-0.74, p <0.001). CONCLUSIONS Among patients with CHB and SLD, metabolic burden dose-dependently increases all-cause, liver-related, and cardiovascular mortality risks. Patients with SLD have a lower mortality risk than those without SLD. Identifying these metabolic dysfunctions is crucial for stratifying the level of risk in daily care. IMPACT AND IMPLICATIONS Concurrent steatotic liver disease (SLD) is prevalent among patients with chronic hepatitis B (CHB); however, the effects of the associated cardiometabolic risk factors on all-cause and cause-specific mortality remain unknown. This study demonstrated that cumulative metabolic burden dose-dependently increased the risks of all-cause, liver-related, and cardiovascular mortality in patients with CHB and SLD. Moreover, new-onset diabetes mellitus, hypertension, and weight gain during the follow-up period further exacerbated these risks. However, patients with SLD had a lower risk of mortality than those without SLD. Thus, routine screening and monitoring of metabolic dysfunctions constitute a key element of daily care for patients with CHB.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Farrash WF, Idris S, Elzubier ME, Khidir EBA, Aslam A, Mujalli A, Almaimani RA, Obaid AA, El-Readi MZ, Alobaidy MA, Salaka A, Shakoori AM, Saleh AM, Minshawi F, Samkari JA, Alshehre SM, Refaat B. Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction-associated steatohepatitis in mice by boosted modulation of metabolic, oxidative stress, and inflammatory pathways. Int J Exp Pathol 2024; 105:219-234. [PMID: 39397269 DOI: 10.1111/iep.12519] [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: 07/12/2024] [Revised: 09/04/2024] [Accepted: 09/13/2024] [Indexed: 10/15/2024] Open
Abstract
Although single treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) or vitamin D3 (VD3) inhibited metabolic dysfunction-associated steatohepatitis (MASH) development in diabetic patients, their combination has not been explored previously. Hence, this study investigated the hepatoprotective effects of SGLT2i (empagliflozin) and/or VD3 against MASH in type 2 diabetic mice. Forty Mice were assigned into negative (NC) and positive (PC) controls, SGLT2i, VD3, and SGLT2i + VD3 groups. All animals, except the NC group, received high-fructose/high-fat diet (8 weeks) followed by diabetes induction. Diabetic mice then received another cycle of high-fructose/high-fat diet (4 weeks) followed by 8 weeks of treatment (five times/week) with SGLT2i (5.1 mg/kg/day) and/or VD3 (410 IU/Kg/day). The PC group demonstrated hyperglycaemia, dyslipidaemia, elevated liver enzymes, and increased non-alcoholic fatty liver disease activity score (NAS) with fibrosis. Hepatic glucose transporting molecule (SGLT2) with lipogenesis (SREBP-1/PPARγ), oxidative stress (MDA/H2O2), inflammation (IL1β/IL6/TNF-α), fibrosis (TGF-β1/α-SMA), and apoptosis (TUNEL/Caspase-3) markers alongside the PI3K/AKT/mTOR pathway increased in the PC group. Conversely, hepatic insulin-dependent glucose transporter (GLUT4), lipolytic (PPARα/INSIG1), antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL-10) molecules with the inhibitor of PI3K/AKT/mTOR pathway (PTEN) decreased in the PC group. Whilst SGLT2i monotherapy outperformed VD3, their combination showed the best attenuation of hyperglycaemia, dyslipidaemia, and fibrosis with the strongest modulation of hepatic glucose-transporting and lipid-regulatory molecules, PI3K/AKT/mTOR pathway, and markers of oxidative stress, inflammation, fibrosis, and apoptosis. This study is the first to reveal boosted hepatoprotection for SGLT2i and VD3 co-therapy against diabetes-induced MASH, possibly via enhanced metabolic control and modulation of hepatic PI3K/AKT/mTOR, anti-inflammatory, anti-oxidative, and anti-fibrotic pathways.
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Affiliation(s)
- Wesam F Farrash
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Shakir Idris
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Mohamed E Elzubier
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Elshiekh B A Khidir
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Akhmed Aslam
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Abdulrahman Mujalli
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Riyad A Almaimani
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmad A Obaid
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Mahmoud Z El-Readi
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
| | - Mohammad A Alobaidy
- Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Afnan Salaka
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Afnan M Shakoori
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Alaa M Saleh
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Faisal Minshawi
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Jamil A Samkari
- Department of Family and Community Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sallwa M Alshehre
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Bassem Refaat
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
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Liu CJ, Seto WK, Yu ML. Dual-etiology MAFLD: the interactions between viral hepatitis B, viral hepatitis C, alcohol, and MAFLD. Hepatol Int 2024; 18:897-908. [PMID: 39115632 DOI: 10.1007/s12072-024-10699-x] [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: 01/31/2024] [Accepted: 05/03/2024] [Indexed: 10/05/2024]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed.
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Affiliation(s)
- Chun-Jen Liu
- Hepatitis Research Center, National Taiwan University College of Medicine and, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Wai Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Pok Fu Lam, China.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Center of Hepatitis Research, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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Danielsson O, Vesterinen T, Arola J, Åberg F, Nissinen MJ. Coexistence of metabolic-associated fatty liver disease and autoimmune or toxic liver disease. Eur J Gastroenterol Hepatol 2024; 36:961-969. [PMID: 38829946 PMCID: PMC11136267 DOI: 10.1097/meg.0000000000002785] [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: 01/25/2024] [Accepted: 04/06/2024] [Indexed: 06/05/2024]
Abstract
Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 million inhabitants) between 2009 and 2019 were collected from patients with AIH, PBC, PSC, or toxic liver disease at the time of diagnosis. MAFLD was diagnosed as macrovesicular steatosis ≥5% together with obesity, type-2 diabetes, or signs of metabolic dysregulation. Of 648 patients included, steatosis was observed in 15.6% (n = 101), of which 94.1% (n = 95) was due to MAFLD. Prevalence of coexisting MAFLD in the four liver diseases varied between 12.4 and 18.2% (P = 0.483). Fibrosis was more severe in MAFLD among patients with toxic liver disease (P = 0.01). Histopathological characteristics otherwise showed similar distribution among MAFLD and non-FLD controls. Alcohol consumption was higher in MAFLD group among patients with AIH or PBC (P < 0.05 for both). In AIH, smoking was more common in patients with coexisting MAFLD (P = 0.034). Prevalence of coexisting MAFLD in other primary liver diseases is lower than reported in general population. Histopathology of MAFLD patients did not clearly differ from non-FLD ones. Alcohol and smoking were associated with MAFLD in AIH.
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Affiliation(s)
- Oscar Danielsson
- Clinic of Gastroenterology, Abdominal Center, Helsinki University Hospital and University of Helsinki
- Doctoral Programme in Clinical Research, University of Helsinki
| | - Tiina Vesterinen
- HUS Diagnostic Center, HUSLAB, Helsinki University Hospital and University of Helsinki
| | - Johanna Arola
- HUS Diagnostic Center, HUSLAB, Helsinki University Hospital and University of Helsinki
- Department of Pathology, Faculty of Medicine, University of Helsinki
| | - Fredrik Åberg
- Abdominal Center, Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Markku J. Nissinen
- Clinic of Gastroenterology, Abdominal Center, Helsinki University Hospital and University of Helsinki
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Li Y, Dai C, Ruan Y, Yang H, Zeng H, Huang R, Wang J, Dai M, Hao J, Wang L, Li J, Yan X, Lu Z, Ji F. Metabolic dysfunction-associated fatty liver disease and nonalcoholic fatty liver disease from clinical to pathological characteristics: a multi-center cross-sectional study in real world. Postgrad Med J 2024; 100:319-326. [PMID: 38272486 DOI: 10.1093/postmj/qgae007] [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] [Received: 07/29/2023] [Revised: 11/17/2023] [Accepted: 01/04/2024] [Indexed: 01/27/2024]
Abstract
BACKGROUND The evaluation of patients with fatty liver as defined by metabolic dysfunction-associated fatty liver disease (MAFLD) in the real world remains poorly researched. This study aimed to analyse the clinical and histological features of patients with MAFLD and nonalcoholic fatty liver disease (NAFLD) and to characterize each metabolic subgroup of MAFLD. METHODS A total of 2563 patients with fatty liver confirmed by ultrasonography and/or magnetic resonance tomography and/or liver biopsy-proven from three hospitals in China were included in the study. Patients were divided into different groups according to diagnostic criteria for MAFLD and NAFLD, and MAFLD into different subgroups. RESULTS There were 2337 (91.2%) patients fitting the MAFLD criteria, and 2095 (81.7%) fitting the NAFLD criteria. Compared to patients with NAFLD, those with MAFLD were more likely to be male, had more metabolic traits, higher liver enzyme levels, and noninvasive fibrosis scores. Among the patients with liver biopsy, the extent of advanced fibrosis in cases with MAFLD was significantly higher than those with NAFLD, 31.8% versus 5.2% (P < .001); there was no significant difference in advanced fibrosis between obese cases and lean individuals in MAFLD (P > .05); MAFLD complicated with diabetes had significantly higher advanced fibrosis than those without diabetes (43.3% and 17.2%, respectively; P < .001). CONCLUSIONS Patients with MAFLD have a higher degree of liver fibrosis than NAFLD patients. In addition, diabetic patients should be screened for fatty liver and liver fibrosis degree.
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Affiliation(s)
- Yan Li
- Graduate School of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Changyong Dai
- Graduate School of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
- Department of Infectious Diseases, Huaian Hospital of Huaian City, Huaian, Jiangsu, 223200, China
| | - Yuhua Ruan
- Graduate School of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Haiqing Yang
- Graduate School of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Huang Zeng
- Graduate School of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China
| | - Jialu Wang
- Graduate School of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Mingjia Dai
- Department of Infection and Hepatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
| | - Jungui Hao
- Department of Infection and Hepatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
| | - Liping Wang
- Department of Infection and Hepatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China
| | - Xuebing Yan
- Department of Infection and Hepatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
| | - Zhonghua Lu
- Department of Liver Disease, Affiliated Wuxi Fifth Hospital of Jiangnan University, Wuxi, Jiangsu, 214011, China
| | - Fang Ji
- Department of Infection and Hepatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
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Kaewdech A, Sripongpun P. Navigating the Nomenclature of Liver Steatosis: Transitioning from NAFLD to MAFLD and MASLD - Understanding Affinities and Differences. SIRIRAJ MEDICAL JOURNAL 2024; 76:234-243. [DOI: 10.33192/smj.v76i4.267556] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The escalating prevalence of non-alcoholic fatty liver disease (NAFLD) represents a significant challenge to public health, with an increasing impact observed across various demographics. This review delivers a comprehensive evaluation of the evolving terminology in steatotic liver disease (SLD), documenting the transition from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD), and progressing to the latest terms, metabolic dysfunction-associated fatty liver disease (MASLD) and MASLD with increased alcohol intake (MetALD). We conducted a comprehensive review of literature discussing the benefits and drawbacks of these nomenclatural changes. Clinical evidence supporting MASLD and MetALD, including the implications of alcohol consumption thresholds on disease classification and outcomes, was analyzed. The “MAFLD” and “MASLD” labels align with the pathophysiology of metabolic diseases, afford a positive disease connotation, and facilitate the identification of more severe diseases, such as significant fibrosis or advanced liver disease. However, the MAFLD criteria may underdiagnose lean, non-overweight, or non-obese individuals with MAFLD. The review underscores the understanding of liver diseases linked to metabolic dysfunction and alcohol use. The shift in terminology marks progress towards a clinical diagnosis that reflects underlying pathophysiology. However, additional studies are necessary to assess the longterm effects of these changes and their efficacy in enhancing patient care and health outcomes.
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Jang TY, Ho CC, Liang PC, Wu CD, Wei YJ, Tsai PC, Hsu PY, Hsieh MY, Lin YH, Hsieh MH, Wang CW, Yang JF, Yeh ML, Huang CF, Chuang WL, Huang JF, Cheng YY, Dai CY, Chen PC, Yu ML. Air pollution associate with advanced hepatic fibrosis among patients with chronic liver disease. Kaohsiung J Med Sci 2024; 40:304-314. [PMID: 37947277 DOI: 10.1002/kjm2.12781] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 10/20/2023] [Accepted: 10/25/2023] [Indexed: 11/12/2023] Open
Abstract
We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti-HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter [PM2.5 ], nitrogen dioxide [NO2 ], ozone [O3 ] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05-4.77; p < 0.001), smoking (OR, 1.79; 95% CI, 1.16-2.74; p = 0.01), age (OR, 1.04; 95% CI, 1.02-1.05; p < 0.001) and PM2.5 (OR, 1.10; 95% CI, 1.05-1.16; p < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM2.5 (β: 0.134; 95% CI: 0.025, 0.243; p = 0.02). There was a dose-dependent relationship between different fibrotic stages and the PM2.5 level (the PM2.5 level in patients with fibrotic stages 0, 1-2 and 3-4: 27.9, 28.4, and 29.3 μg/m3 , respectively; trend p < 0.001). Exposure to PM2.5 , as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dose-dependent correlation between PM2.5 levels and the severity of hepatic fibrosis.
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Affiliation(s)
- Tyng-Yuan Jang
- Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University and National Health Research Institutes, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Ping-Tung, Taiwan
| | - Chi-Chang Ho
- Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Da Wu
- Department of Geomatics, National Cheng Kung University, Tainan, Taiwan
- Innovation and Development Center of Sustainable Agriculture, National Chung Hsing University, Tainan, Taiwan
| | - Yu-Ju Wei
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jeng-Fu Yang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ya-Yun Cheng
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pau-Chung Chen
- Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan
- Department of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan
- National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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Huang SC, Su TH, Tseng TC, Chen CL, Hsu SJ, Liu CH, Liao SH, Hong CM, Lan TY, Yang HC, Liu CJ, Chen PJ, Kao JH. Metabolic Dysfunction-Associated Steatotic Liver Disease Facilitates Hepatitis B Surface Antigen Seroclearance and Seroconversion. Clin Gastroenterol Hepatol 2024; 22:581-590.e6. [PMID: 37871842 DOI: 10.1016/j.cgh.2023.09.040] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/22/2023] [Accepted: 09/29/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND & AIMS Hepatitis B surface antigen (HBsAg) seroclearance is the goal of functional cure for hepatitis B virus (HBV) infection. However, the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on this favorable outcome remains unclear. METHODS Patients with chronic hepatitis B (CHB) were consecutively recruited. MASLD was defined by the newly proposed disease criteria. Cumulative incidences and associated factors of HBsAg seroclearance/seroconversion were compared between the MASLD and non-MASLD groups. RESULTS From 2006 to 2021, 4084 treatment-naive hepatitis B e antigen (HBeAg)-negative CHB patients were included. At baseline, CHB patients with concurrent MASLD (n = 887) had significantly lower levels of HBsAg and HBV DNA than the non-MASLD group (n = 3197). During a median follow-up of 5.0 years, MASLD was associated with a higher likelihood of HBsAg seroclearance (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.10-1.85; P = .007), and the accumulation of individual metabolic dysfunctions additively facilitated HBsAg seroclearance. In addition, a higher rate of HBsAg seroconversion was observed in patients with MASLD versus those without MASLD (aHR, 1.37; 95% CI, 1.00-1.86; P = .049). In sensitivity analysis, patients with intermittent MASLD had an intermediate probability of HBsAg seroclearance. After balancing clinical and virologic profiles by inverse probability of treatment weighting (IPTW), MASLD was still associated with a higher HBsAg seroclearance rate (IPTW-adjusted HR, 1.41; 95% CI, 1.09-1.84; P = .010). CONCLUSIONS In untreated HBeAg-negative CHB patients, concurrent MASLD is associated with higher rates of HBsAg seroclearance and seroconversion. Metabolic dysfunctions have additive effects on the functional cure of CHB.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Huang HK, Li YM, Xu CF. Pre-MASLD: Should it be defined separately? Hepatobiliary Pancreat Dis Int 2024; 23:1-3. [PMID: 37838529 DOI: 10.1016/j.hbpd.2023.10.003] [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: 09/05/2023] [Accepted: 09/25/2023] [Indexed: 10/16/2023]
Affiliation(s)
- Hang-Kai Huang
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - You-Ming Li
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Cheng-Fu Xu
- Department of Gastroenterology, Zhejiang Provincial Clinical Research Center for Digestive Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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12
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Huang SC, Kao JH. The interplay between chronic hepatitis B and diabetes mellitus: A narrative and concise review. Kaohsiung J Med Sci 2024; 40:6-10. [PMID: 37732697 DOI: 10.1002/kjm2.12762] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/02/2023] [Accepted: 09/05/2023] [Indexed: 09/22/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder among individuals with chronic hepatitis B (CHB), contributing to additional adverse impacts on both hepatic and extrahepatic systems. Existing evidence suggests a potential positive association between CHB and the development of insulin resistance and T2DM. The presence of T2DM in CHB patients is associated with an increased risk of liver fibrosis, cirrhosis, decompensation, and hepatocellular carcinoma (HCC) occurrence. Moreover, it elevates the risk of non-liver cancers and all-cause mortality in this population. T2DM also serves as the key element in metabolic dysfunction-associated steatotic liver disease, which is prevalent in the CHB population. Although specific guidelines for managing T2DM in CHB patients have not been proposed, some studies indicated that intensive glycemic control may benefit the prognosis of these patients. Additionally, specific antidiabetic agents, such as metformin and thiazolidinediones, promise to reduce HCC risk. However, unresolved questions, including the optimal glycemic control target and the selection of antidiabetic agents for CHB patients, remain and thus warrant further investigations through well-designed prospective trials. Implementing a standardized protocol encompassing regular monitoring, risk stratification, and early intervention using a multidisciplinary framework may improve the outcomes of diabetic CHB patients.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Colaci C, Gambardella ML, Maria Scarlata GG, Boccuto L, Colica C, Luzza F, Scarpellini E, Mendez-Sanchez N, Abenavoli L. Dysmetabolic comorbidities and non-alcoholic fatty liver disease: a stairway to metabolic dysfunction-associated steatotic liver disease. HEPATOMA RESEARCH 2024; 10:16. [DOI: 10.20517/2394-5079.2023.134] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. This term does not describe the pathogenetic mechanisms and complications associated with NAFLD. The new definition, Metabolic Dysfunction-associated Steatotic Liver disease (MASLD), emphasizes the relationship between NAFLD and cardiometabolic comorbidities. Cardiovascular disease features, such as arterial hypertension and atherosclerosis, are frequently associated with patients with MASLD. Furthermore, these patients have a high risk of developing neoplastic diseases, primarily hepatocellular carcinoma, but also extrahepatic tumors, such as esophageal, gastric, and pancreatic cancers. Moreover, several studies showed the correlation between MASLD and endocrine disease. The imbalance of the gut microbiota, systemic inflammation, obesity, and insulin resistance play a key role in the development of these complications. This narrative review aims to clarify the evolution from NAFLD to the new nomenclature MASLD and evaluate its complications.
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Huang SC, Su TH, Tseng TC, Chen CL, Hsu SJ, Liao SH, Hong CM, Liu CH, Lan TY, Yang HC, Liu CJ, Chen PJ, Kao JH. Distinct effects of hepatic steatosis and metabolic dysfunction on the risk of hepatocellular carcinoma in chronic hepatitis B. Hepatol Int 2023; 17:1139-1149. [PMID: 37247045 DOI: 10.1007/s12072-023-10545-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/29/2023] [Indexed: 05/30/2023]
Abstract
OBJECTIVE Chronic hepatitis B (CHB) and metabolic dysfunction-associated fatty liver disease (MAFLD) are the leading causes of hepatocellular carcinoma (HCC). We aim to explore the impact of concurrent MAFLD on the risk of HCC in CHB. METHODS Patients with CHB were consecutively recruited from 2006 to 2021. MAFLD was defined by steatosis and either obesity, diabetes mellitus, or other metabolic abnormalities. The cumulative incidence of HCC and associated factors were compared between the MAFLD and non-MAFLD groups. RESULTS 10,546 treatment-naïve CHB patients were included with a median follow-up of 5.1 years. CHB patients with MAFLD (n = 2212) had fewer hepatitis B e antigen (HBeAg)-positivity, lower HBV DNA levels, and Fibrosis-4 index compared with the non-MAFLD group (n = 8334). MAFLD was independently associated with a 58% reduced risk of HCC (adjusted hazard ratio [aHR] 0.42, 95% confidence interval [CI] 0.25-0.68, p < 0.001). Furthermore, steatosis and metabolic dysfunction had distinct effects on HCC. Steatosis was protective against HCC (aHR 0.45, 95% CI 0.30-0.67, p < 0.001), while a greater burden of metabolic dysfunction increased the risk (aHR 1.40 per dysfunction increase, 95% CI 1.19-1.66, p < 0.001). The protective effect of MAFLD was further confirmed in analysis with inverse probability of treatment weighting (IPTW), patients who had undergone antiviral therapy, those with probable MAFLD, and after multiple imputation for missing data. CONCLUSIONS Concurrent hepatic steatosis is independently associated with a lower risk of HCC, whereas the increasing burden of metabolic dysfunction aggravates the risk of HCC in untreated CHB patients.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Klaric KA, Parai JL, Kepron CA, Walker AE, Milroy CM. Postmortem survey of haemoglobin A1c, non-alcoholic steatohepatitis and liver fibrosis within a general population. J Clin Pathol 2023; 76:606-611. [PMID: 35534202 DOI: 10.1136/jclinpath-2021-207998] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 04/14/2022] [Indexed: 11/04/2022]
Abstract
AIMS Non-alcoholic steatohepatitis (NASH), fatty liver disease and fibrosis are associated with diabetes mellitus and obesity. Previous autopsy series have reported prevalence of fatty liver disease to be 11%-24%. Recent studies, using imaging and serology, suggest a prevalence of 20%-35%, NASH of 5% and advanced fibrosis of 2%-3%. We examined the prevalence of NASH and liver fibrosis in a general autopsy population. METHODS A cross-sectional study of consecutive, adult, medicolegal autopsies over a 1-year period was conducted. Liver sections were scored for fibrosis, inflammation and steatosis using a modified NASH scoring system. Stepwise logistic regression was used to identify associations between NASH or moderate/severe fibrosis and several clinicopathological parameters, including postmortem haemoglobin A1c (HbA1c). RESULTS Of 376 cases, 86 (22.9%) were classified as NASH. Prevalence of diabetes mellitus, body mass index (BMI) and postmortem HbA1c were significantly higher in NASH cases (39.5%, 32.3 kg/m2 and 6.88%) than non-NASH cases (12.1%, 27.0 kg/m2 and 5.73%). Decedents with moderate/severe fibrosis (6.9%) had higher prevalence of diabetes, BMI and HbA1c (50%, 31.4 kg/m2 and 6.7%) compared with those with no/mild fibrosis (16%, 28 kg/m2 and 5.9%). HbA1c ≥7% was found to be an independent predictor of NASH (OR 5.11, 95% CI 2.61 to 9.98) and advanced fibrosis (OR 3.94, 95% CI 1.63 to 9.53). CONCLUSIONS NASH and advanced fibrosis were higher in our general adult autopsy population compared with previously published estimates. This is a large series with histological evaluation showing that HbA1c >7.0% is independently associated with NASH and advanced fibrosis.
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Affiliation(s)
- Kristina-Ana Klaric
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
| | - Jacqueline Louise Parai
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Charis Anthea Kepron
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Alfredo Eugene Walker
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Christopher Mark Milroy
- Department of Pathology and Laboratory Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- Pathology and Laboratory Medicine, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
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Otsubo N, Fukuda T, Cho G, Ishibashi F, Yamada T, Monzen K. Utility of Indices Obtained during Medical Checkups for Predicting Fatty Liver Disease in Non-obese People. Intern Med 2023; 62:2307-2319. [PMID: 36517035 PMCID: PMC10484762 DOI: 10.2169/internalmedicine.1097-22] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 10/31/2022] [Indexed: 12/15/2022] Open
Abstract
Objective To predict fatty liver disease (FLD), including nonalcoholic FLD (NAFLD) and metabolic dysfunction-associated FLD (MAFLD), from blood tests and anthropometric measurements, the fatty liver index (FLI) and triglyceride glucose-body mass index (TyG-BMI) have been reported as promising indicators. We evaluated the predictive ability of several indices, including the waist circumference, BMI, FLI and TyG-BMI, that might predict FLD in non-obese individuals undergoing health checkups. Methods This retrospective observational study enrolled non-obese subjects who underwent abdominal ultrasonography between May 1, 2015, and June 30, 2022. Obesity was defined as a BMI <25 kg/m2. FLD was diagnosed by abdominal ultrasonography. Using a receiver operating characteristic analysis, we examined the predictive validity of indices for NAFLD and MAFLD by calculating the area under the curve (AUC). Results Of the 24,825 subjects (mean age 44.3±10.0 years old; 54% men) enrolled in this examination of the association of indices, including FLI and TyG-BMI, with NAFLD, NAFLD was diagnosed in 3,619 (27%) men and 733 (6%) women. In both men and women, the FLI and TyG-BMI had significantly higher AUC values for NAFLD prediction than the other indicators (FLI: 0.786 for men and 0.875 for women, TyG-BMI: 0.783 for men and 0.868 for women). In analyses of subjects with a BMI <23 kg/m2, the superiority of the FLI and TyG-BMI remained unchanged. The FLI and TyG-BMI also had significantly higher AUC values for MAFLD prediction than the other indicators. Conclusion The FLI and TyG-BMI had a particularly high predictive ability for NAFLD and MAFLD in non-obese subjects.
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Affiliation(s)
- Naoya Otsubo
- Shinjuku Tsurukame Clinic, Japan
- Department of Endocrinology and Metabolism, Tokyo Metropolitan Health and Hospitals Corporation Okubo Hospital, Japan
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan
| | - Tatsuya Fukuda
- Department of Endocrinology and Metabolism, Tokyo Metropolitan Health and Hospitals Corporation Okubo Hospital, Japan
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan
- Mirraza Shinjuku Tsurukame Clinic, Japan
| | - Genhin Cho
- Mirraza Shinjuku Tsurukame Clinic, Japan
| | - Fumiaki Ishibashi
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Japan
- Koganei Tsurukame Clinic, Japan
| | - Tetsuya Yamada
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan
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Lim TS, Chun HS, Kim SS, Kim JK, Lee M, Cho HJ, Kim SU, Cheong JY. Fibrotic Burden in the Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes. Gut Liver 2023; 17:610-619. [PMID: 36799062 PMCID: PMC10352051 DOI: 10.5009/gnl220400] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/24/2022] [Accepted: 11/29/2022] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND/AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), lean/normal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. METHODS This cross-sectional multicenter study was done in cohorts of subjects who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,651 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the nonalcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. RESULTS The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the no MAFLD group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09 to 9.51), 2.81 (1.12 to 6.39), and 9.52 (4.46 to 20.36) in OW-MAFLD, lean-MAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78 to 1.36), 1.14 (0.82 to 1.57), and 1.97 (1.48 to 2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD. CONCLUSIONS Fibrotic burden in the liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.
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Affiliation(s)
- Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yongin Severance Hospital, Yongin, Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
| | - Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Ja Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yongin Severance Hospital, Yongin, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea
| | - Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
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Yang Z, Yang J, Cai J, Zhang XJ, Zhang P, She ZG, Li H. The Transition of Cardiovascular Disease Risks from NAFLD to MAFLD. Rev Cardiovasc Med 2023; 24:157. [PMID: 39077530 PMCID: PMC11264127 DOI: 10.31083/j.rcm2406157] [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: 11/17/2022] [Revised: 01/19/2023] [Accepted: 01/31/2023] [Indexed: 07/31/2024] Open
Abstract
The increased burden of nonalcoholic fatty liver disease (NAFLD) parallels the increased incidence of overweight and metabolic syndrome worldwide. Because of the close relationship between metabolic disorders and fatty liver disease, a new term, metabolic-related fatty liver disease (MAFLD), was proposed by a group of experts to more precisely describe fatty liver disease resulting from metabolic disorders. According to the definitions, MAFLD and NAFLD populations have considerable discrepancies, but overlap does exist. This new definition has a nonnegligible impact on clinical practices, including diagnoses, interventions, and the risk of comorbidities. Emerging evidence has suggested that patients with MAFLD have more metabolic comorbidities and an increased risk of all-cause mortality, particularly cardiovascular mortality than patients with NAFLD. In this review, we systemically summarized and compared the risk and underlying mechanisms of cardiovascular disease (CVD) in patients with NAFLD or MAFLD.
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Affiliation(s)
- Zifeng Yang
- Department of Cardiology, Renmin Hospital of Wuhan University, 430000 Wuhan, Hubei, China
- Institute of Model Animal, Wuhan University, 430000 Wuhan, Hubei, China
| | - Juan Yang
- Department of Cardiology, Huanggang Central hospital of Yangtze University, 438000 Huanggang, Hubei, China
- Huanggang Institute of Translational Medicine, 438000 Huanggang, Hubei, China
| | - Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, 410000 Changsha, Hunan, China
| | - Xiao-Jing Zhang
- Institute of Model Animal, Wuhan University, 430000 Wuhan, Hubei, China
- School of Basic Medical Sciences, Wuhan University, 430000 Wuhan, Hubei, China
| | - Peng Zhang
- Institute of Model Animal, Wuhan University, 430000 Wuhan, Hubei, China
- School of Basic Medical Sciences, Wuhan University, 430000 Wuhan, Hubei, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, 430000 Wuhan, Hubei, China
- Institute of Model Animal, Wuhan University, 430000 Wuhan, Hubei, China
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, 430000 Wuhan, Hubei, China
- Institute of Model Animal, Wuhan University, 430000 Wuhan, Hubei, China
- Huanggang Institute of Translational Medicine, 438000 Huanggang, Hubei, China
- School of Basic Medical Sciences, Wuhan University, 430000 Wuhan, Hubei, China
- Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, 341000 Ganzhou, Jiangxi, China
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19
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Chang M, Shao Z, Shen G. Association between triglyceride glucose-related markers and the risk of metabolic-associated fatty liver disease: a cross-sectional study in healthy Chinese participants. BMJ Open 2023; 13:e070189. [PMID: 37130686 PMCID: PMC10163481 DOI: 10.1136/bmjopen-2022-070189] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 04/19/2023] [Indexed: 05/04/2023] Open
Abstract
OBJECTIVES This study aimed to evaluate the performance of the triglyceride glucose (TyG) index and its related markers in predicting metabolic-associated fatty liver disease (MAFLD) in healthy Chinese participants. DESIGN This was a cross-sectional study. SETTING The study was conducted at Health Management Department of the Affiliated Hospital of Xuzhou Medical University. PARTICIPANTS A total of 20 922 asymptomatic Chinese participants (56% men) were enrolled. OUTCOME MEASURES Hepatic ultrasonography was performed to diagnose MAFLD based on the latest diagnostic criteria. The TyG, TyG-body mass (TyG-BMI) and TyG-waist circumference indices were calculated and analysed. RESULTS Compared with the lowest quartile of the TyG-BMI, the adjusted ORs and 95% CIs for MAFLD were 20.76 (14.54 to 29.65), 92.33 (64.61 to 131.95) and 380.87 (263.25 to 551.05) in the second, third and fourth quartiles, respectively. According to the subgroup analysis, the TyG-BMI in the female and the lean groups (BMI<23 kg/m2) showed the strongest predictive value, with optimal cut-off values for MAFLD of 162.05 and 156.31, respectively. The areas under the receiver operating characteristic curves in female and lean groups were 0.933 (95% CI 0.927 to 0.938) and 0.928 (95% CI 0.914 to 0.943), respectively, with 90.7% sensitivity and 81.2% specificity in female participants with MAFLD and 87.2% sensitivity and 87.1% specificity in lean participants with MAFLD. The TyG-BMI index demonstrated superior predictive ability for MAFLD compared with other markers. CONCLUSIONS The TyG-BMI is an effective, simple and promising tool for predicting MAFLD, especially in lean and female participants.
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Affiliation(s)
- Mingxing Chang
- Health Management Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Zhihao Shao
- Health Management Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Guifang Shen
- Health Management Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
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20
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Lim GEH, Tang A, Ng CH, Chin YH, Lim WH, Tan DJH, Yong JN, Xiao J, Lee CWM, Chan M, Chew NW, Xuan Tan EX, Siddiqui MS, Huang D, Noureddin M, Sanyal AJ, Muthiah MD. An Observational Data Meta-analysis on the Differences in Prevalence and Risk Factors Between MAFLD vs NAFLD. Clin Gastroenterol Hepatol 2023; 21:619-629.e7. [PMID: 34871813 DOI: 10.1016/j.cgh.2021.11.038] [Citation(s) in RCA: 138] [Impact Index Per Article: 69.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 11/12/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD. METHODS Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis. RESULTS Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval [CI], 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P < .001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD. CONCLUSIONS There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.
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Affiliation(s)
- Grace En Hui Lim
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Ansel Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yip Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chloe Wen-Min Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Mark Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Nicholas Ws Chew
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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21
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Tang SY, Tan JS, Pang XZ, Lee GH. Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact. World J Gastroenterol 2023; 29:549-560. [PMID: 36688021 PMCID: PMC9850940 DOI: 10.3748/wjg.v29.i3.549] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 11/14/2022] [Accepted: 12/23/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND In 2020, an international expert panel proposed a new definition of fatty liver: Metabolic dysfunction-associated fatty liver disease (MAFLD). The MAFLD added the criteria for defining metabolic dysfunctions, which are high-risk factors for liver-related and cardiovascular events. Contrary to the non-alcoholic fatty liver disease (NAFLD) definition, it allows the coexistence of MAFLD and significant alcohol use in the same patient.
AIM To review the existing data that evaluate the clinical profile and long-term outcome difference between the patients identified as MAFLD and NAFLD.
METHODS Databases MEDLINE via PubMed and EMBASE were searched and relevant publications up to June 28, 2022 were assessed. Studies were included if they involved human participants diagnosed with MAFLD.
RESULTS A total of 2324 records were reviewed, of which 1575 duplicate citations were removed. Of the 2324 records screened, 207 articles were excluded, and 542 articles were assessed for their eligibility, for which 511 were excluded. The remaining 31 articles were selected for review. MAFLD diagnostic criteria were able to identify more individuals with fatty liver. Studies have shown that patients included using the MAFLD criteria were associated with higher risks of hepatic fibrosis when compared to NAFLD. All-cause mortality, cardiovascular disease-related, and cancer-related mortality were shown to be higher in MAFLD patients. MAFLD patients also had higher baseline metabolic derangement, and risks of developing obesity, diabetes, and cardiovascular events. Of the 3 subtypes, diabetes mellitus has the strongest association with negative outcomes, followed by metabolic dysfunction and elevated body mass index. Within the subtypes of MAFLD, patients with more metabolic conditions at the time of diagnosis had worse hepatic and liver injury compared to those with a single metabolic condition.
CONCLUSION MAFLD is a new definition of fatty liver disease that is gaining increasing acceptance. It is based on empirical clinical practice on positive inclusion of metabolic risk factors and recent evidence suggests that it helps to identify patients with higher risk for liver-related as well as cardiovascular events.
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Affiliation(s)
- Si-Ying Tang
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore 119228, Singapore
| | - Jian Shiun Tan
- Yong Loo Lin School of Medicine, Singapore 117597, Singapore
| | - Xian-Zheng Pang
- Yong Loo Lin School of Medicine, Singapore 117597, Singapore
| | - Guan-Huei Lee
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore 119228, Singapore
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Pipitone RM, Ciccioli C, Infantino G, La Mantia C, Parisi S, Tulone A, Pennisi G, Grimaudo S, Petta S. MAFLD: a multisystem disease. Ther Adv Endocrinol Metab 2023; 14:20420188221145549. [PMID: 36726391 PMCID: PMC9885036 DOI: 10.1177/20420188221145549] [Citation(s) in RCA: 98] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/26/2022] [Indexed: 01/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as 'Metabolic dysfunction-Associated Fatty Liver Disease' (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only - as expected - liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form - nonalcoholic/metabolic dysfunction-associated steatohepatitis - to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.
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Affiliation(s)
- Rosaria Maria Pipitone
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Carlo Ciccioli
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Giuseppe Infantino
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Claudia La Mantia
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Stefanie Parisi
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Adele Tulone
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Grazia Pennisi
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
| | - Stefania Grimaudo
- Section of Gastroenterology and Hepatology,
PROMISE, University of Palermo, Palermo, Italy
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23
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Song D, Ge Q, Chen M, Bai S, Lai X, Huang G, Liu M, Lin M, Xu J, Dong F. Development and Validation of a Nomogram for Prediction of the Risk of MAFLD in an Overweight and Obese Population. J Clin Transl Hepatol 2022; 10:1027-1033. [PMID: 36381091 PMCID: PMC9634768 DOI: 10.14218/jcth.2021.00317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/13/2021] [Accepted: 12/27/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Metabolic associated fatty liver disease (MAFLD) is a serious condition, and a simple method is needed for practitioners to identify patients with the disease and have a high risk of disease progression. METHODS We developed and validated a nomogram for fatty liver disease and reclassified the risk factors for MAFLD. The development cohort had 335 patients who received bioelectrical impedance analysis and liver ultrasound attenuation measurements at Shenzhen People's Hospital between September 2020 and June 2021. The validation cohort had 200 patients from other hospitals who received the same evaluation. A random forest procedure and binary logistic analysis were used to screen for risk factors, establish a fatty liver disease predictive model, and forecast the risk of MAFLD. The performance of the nomogram was evaluated by measurement of discrimination, calibration, and clinical usefulness. RESULTS The nomogram provided good predictions in a model that included body mass index (BMI) and waist circumference. The areas under the curve of the nomogram were 0.793 in the development cohort and 0.774 in the validation cohort. The nomogram performed well for calibration, category-free net reclassification improvement, and integrated discrimination improvement. Decision curve analysis indicated the nomogram performed better than BMI for predicting net outcome. CONCLUSIONS The nomogram was an effective screening tool for fatty liver disease, and for those overweight individuals, may help physicians make appropriate decisions regarding treatment of MAFLD.
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Affiliation(s)
- Di Song
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Qian Ge
- Department of Nutrition, Shenzhen People’s Hospital, Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Ming Chen
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Song Bai
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Xiaoshu Lai
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Gege Huang
- Department of Nutrition, Shenzhen People’s Hospital, Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Mengmeng Liu
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Miaofang Lin
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Jinfeng Xu
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
| | - Fajin Dong
- Department of Ultrasonography, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China
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24
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Cheng YM, Wang CC, Kao JH. Metabolic associated fatty liver disease better identifying patients at risk of liver and cardiovascular complications. Hepatol Int 2022; 17:350-356. [PMID: 36471232 DOI: 10.1007/s12072-022-10449-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 11/04/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND/PURPOSE A nomenclature of "metabolic associated fatty liver disease" (MAFLD) with a new definition was proposed in 2020 instead of the previous "non-alcoholic fatty liver disease" (NAFLD). Whether it better coheres with the clinical demand remains controversial. METHODS The participants with fatty liver on ultrasonography in Taiwan bio-bank cohorts were included. MAFLD is defined as the presence of fatty liver, plus any of the following three conditions: overweight/obesity, type 2 diabetes mellitus (DM), or metabolic dysfunction. The severity of liver fibrosis was determined using fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS). The risk of atherosclerotic cardiovascular disease was assessed using intima-media thickness (IMT) or plaques of carotid duplex ultrasound. RESULTS A total of 9,719 subjects (ages 55.9 ± 10.8; males 42.6%) were distributed among 4 groups: "overlapping group", "MAFLD only", "NAFLD only", and "neither fatty liver disease (FLD)" with the percentages of 79.7, 12, 7.1, and 1.2%, respectively. Compared with NAFLD patients, MAFLD patients had a greater percentage of males, higher levels of BMI, waist circumference, HbA1c, and triglyceride. In addition, they had higher levels of serum ALT, AST, GGT, fatty liver index (FLI), NFS, and IMT, but no difference in FIB-4 index and the percentage of carotid plaques. To note, "MAFLD only group" had greater levels of AST, ALT, GGT, FLI, FIB-4, NFS, IMT and a higher percentage of carotid plaques than the "NAFLD only group". CONCLUSION The grand, population-based study showed MAFLD with new diagnostic criteria to aid in identifying a greater number of high-risk patients of metabolic, liver, and cardiovascular complications, suggesting MAFLD may be a better nomenclature than NAFLD in clinical practice.
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Zeng J, Fan JG. From NAFLD to MAFLD: Not just a change in the name. Hepatobiliary Pancreat Dis Int 2022; 21:511-513. [PMID: 35613992 DOI: 10.1016/j.hbpd.2022.05.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/15/2022] [Indexed: 02/05/2023]
Affiliation(s)
- Jing Zeng
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
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Perdomo CM, Núñez-Córdoba JM, Ezponda A, Mendoza FJ, Ampuero J, Bastarrika G, Frühbeck G, Escalada J. Cardiometabolic characterization in metabolic dysfunction–associated fatty liver disease. Front Med (Lausanne) 2022; 9:1023583. [PMID: 36341262 PMCID: PMC9632176 DOI: 10.3389/fmed.2022.1023583] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 10/07/2022] [Indexed: 11/16/2022] Open
Abstract
Background To better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes. Methods Cross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography. Results Compared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively). Conclusion MAFLD–T2D and MAFLD–OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.
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Affiliation(s)
- Carolina M. Perdomo
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
- *Correspondence: Carolina M. Perdomo
| | - Jorge M. Núñez-Córdoba
- Research Support Service, Central Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain
| | - Ana Ezponda
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain
| | | | - Javier Ampuero
- Department of Gastroenterology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Sevilla, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Gorka Bastarrika
- Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain
| | - Gema Frühbeck
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
- IdiSNA (Instituto de Investigación en la Salud de Navarra), Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Javier Escalada
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
- IdiSNA (Instituto de Investigación en la Salud de Navarra), Pamplona, Spain
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
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Hepatic steatosis leads to overestimation of liver stiffness measurement in both chronic hepatitis B and metabolic-associated fatty liver disease patients. Clin Res Hepatol Gastroenterol 2022; 46:101957. [PMID: 35609821 DOI: 10.1016/j.clinre.2022.101957] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/12/2022] [Accepted: 05/20/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND The impact of hepatic steatosis on liver stiffness measurement (LSM) in both chronic hepatitis B(CHB) and metabolic-associated fatty liver disease (MAFLD) remains controversial. AIMS To determine whether LSM is affected by hepatic steatosis in CHB-MAFLD. METHODS Hepatic steatosis and liver fibrosis were assessed by histological and noninvasively methods. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance of LSM. RESULTS The prevalence of MAFLD in CHB patients (n = 436)was 47.5% (n = 207). For patients with low amounts of fibrosis (F0-1 and F0-2), the median LSM was 8.8 kPa and 9.2 kPa in patients with moderate- severe steatosis,which was significantly higher than that in patients with none-mild steatosis (P < 0.05) . The positive predictive value(PPV) was lower for LSM identifying significant fibrosis (F ≥ 2) as well as severe fibrosis (F ≥ 3) in group which controlled attenuation parameter(CAP) ≥ 268 dB/m than its counterpart(68.2% vs 84.6% and 24.3% vs 45.0%). The AUROC of LSM detected F ≥ 2 was 0.833 at a cutoff of 8.8 kPa and 0.873 at a cutoff of 7.0 kPa in patients with CAP ≥ 268 and CAP < 268, respectively. CONCLUSIONS The presence of moderate-severe steatosis, detected by histology or CAP, should be taken into account to avoid overestimation of LSM.
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Chan KE, Koh TJL, Tang ASP, Quek J, Yong JN, Tay P, Tan DJH, Lim WH, Lin SY, Huang D, Chan M, Khoo CM, Chew NWS, Kaewdech A, Chamroonkul N, Dan YY, Noureddin M, Muthiah M, Eslam M, Ng CH. Global Prevalence and Clinical Characteristics of Metabolic-associated Fatty Liver Disease: A Meta-Analysis and Systematic Review of 10 739 607 Individuals. J Clin Endocrinol Metab 2022; 107:2691-2700. [PMID: 35587339 DOI: 10.1210/clinem/dgac321] [Citation(s) in RCA: 183] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Metabolic-associated fatty liver disease (MAFLD) was proposed as a better definition of nonalcoholic fatty liver disease (NAFLD) to encompass the metabolic dysregulation associated with NAFLD. This redefinition challenges our understanding of the disease. Hence, this study sought to conduct an updated analysis of the prevalence, clinical characteristics, and associated factors of MAFLD, with a further sensitivity analysis done based on lean and nonobese MAFLD individuals. METHODS Medline and Embase databases were searched to include articles on MAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Associating factors were evaluated in conventional pairwise meta-analysis with sensitivity analysis on lean and nonobese MAFLD. RESULTS From pooled analysis involving 3 320 108 individuals, the overall prevalence of MAFLD was 38.77% (95% CI 32.94% to 44.95%); 5.37% (95% CI 4.36% to 6.59%) and 29.78% (95% CI 26.06% to 33.79%) of lean and nonobese individuals, respectively, had MAFLD. Metabolic complications such as hypertension [odds ratio (OR) 2.63, 95% CI 1.85 to 3.74, P < 0.0001 and OR 2.03; 95% CI 1.74 to 2.38, P < 0.0001, respectively] and diabetes (OR 3.80, 95% CI 2.65 to 5.43, P < 0.0001 and OR 3.46, 95% CI 2.81 to 4.27, P < 0.0001, respectively) were found as significant associating factors associated with lean and nonobese MAFLD. CONCLUSIONS This meta-analysis supports previous studies in reporting MAFLD to affect more than a third of the global population. While exploration of the pathogenic basis of fatty liver disease without metabolic dysregulation is required, the emphasis on management of concomitant metabolic disease in MAFLD can improve multidisciplinary efforts in managing the complex disease.
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Affiliation(s)
- Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Tiffany Jia Ling Koh
- Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Phoebe Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mark Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Chin Meng Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore
| | - Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Apichat Kaewdech
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Yock Young Dan
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Centre, Los Angeles, CA,USA
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, Australia
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Metabolic dysfunction-associated fatty liver disease and chronic hepatitis B. J Formos Med Assoc 2022; 121:2148-2151. [PMID: 35981929 DOI: 10.1016/j.jfma.2022.07.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/17/2022] [Accepted: 07/31/2022] [Indexed: 02/07/2023]
Abstract
Fatty liver disease and chronic hepatitis B (CHB) are the major causes for chronic liver diseases and the associated adverse outcomes. Concurrent hepatic steatosis has been found to inversely correlate with hepatitis B virus (HBV) activity both in vivo and in vitro; however, the subsequent effects on the prognosis, including advanced fibrosis and hepatocellular carcinoma (HCC) development, remain diverse and inconclusive. Although the newly-proposed criteria of metabolic dysfunction-associated fatty liver disease (MAFLD) help raise disease awareness and facilitate timely diagnosis and management, its clinical impact on patients with CHB, especially after taking the metabolic dysfunction into consideration, is largely unknown and warrants comprehensive investigations to improve the management of CHB population. In this review, these relevant issues are summarized and discussed.
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Lee JI. Fatty Liver Disease and Cardiovascular Risk: Impact of Metabolic Dysfunctions. Gut Liver 2022; 16:497-498. [PMID: 35843683 PMCID: PMC9289830 DOI: 10.5009/gnl220276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Affiliation(s)
- Jung Il Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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31
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Wang TY, Wang RF, Bu ZY, Targher G, Byrne CD, Sun DQ, Zheng MH. Association of metabolic dysfunction-associated fatty liver disease with kidney disease. Nat Rev Nephrol 2022; 18:259-268. [PMID: 35013596 DOI: 10.1038/s41581-021-00519-y] [Citation(s) in RCA: 120] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2021] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in more than 5% of hepatocytes in the absence of excessive alcohol consumption and other secondary causes of hepatic steatosis. In 2020, the more inclusive term metabolic (dysfunction)-associated fatty liver disease (MAFLD) - defined by broader diagnostic criteria - was proposed to replace the term NAFLD. The new terminology and revised definition better emphasize the pathogenic role of metabolic dysfunction and uses a set of definitive, inclusive criteria for diagnosis. Diagnosis of MAFLD is based on evidence of hepatic steatosis (as assessed by liver biopsy, imaging techniques or blood biomarkers and scores) in persons who are overweight or obese and have type 2 diabetes mellitus or metabolic dysregulation, regardless of the coexistence of other liver diseases or excessive alcohol consumption. The known association between NAFLD and chronic kidney disease (CKD) and our understanding that CKD can occur as a consequence of metabolic dysfunction suggests that individuals with MAFLD - who by definition have fatty liver and metabolic comorbidities - are at increased risk of CKD. In this Perspective article, we discuss the clinical associations between MAFLD and CKD, the pathophysiological mechanisms by which MAFLD may increase the risk of CKD and the potential drug treatments that may benefit both conditions.
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Affiliation(s)
- Ting-Yao Wang
- Department of Nephrology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Rui-Fang Wang
- Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Zhi-Ying Bu
- Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Christopher D Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Dan-Qin Sun
- Department of Nephrology, the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China.
- Affiliated Wuxi Clinical College of Nantong University, Wuxi, China.
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
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32
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Kawaguchi T, Tsutsumi T, Nakano D, Eslam M, George J, Torimura T. MAFLD enhances clinical practice for liver disease in the Asia-Pacific region. Clin Mol Hepatol 2022; 28:150-163. [PMID: 34753279 PMCID: PMC9013618 DOI: 10.3350/cmh.2021.0310] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/04/2021] [Accepted: 11/07/2021] [Indexed: 11/11/2022] Open
Abstract
Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in lean/normal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and nonspecialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in lean/normal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.
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Affiliation(s)
- Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Tsubasa Tsutsumi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, New South Wales, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, New South Wales, Australia
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Refaat B, Abdelghany AH, Ahmad J, Abdalla OM, Elshopakey GE, Idris S, El-Boshy M. Vitamin D 3 enhances the effects of omega-3 oils against metabolic dysfunction-associated fatty liver disease in rat. Biofactors 2022; 48:498-513. [PMID: 34767670 DOI: 10.1002/biof.1804] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/22/2021] [Indexed: 12/11/2022]
Abstract
This study investigated the effects of omega-3 oils (OM) and/or vitamin D3 (VD) against metabolic dysfunction-associated fatty liver disease (MAFLD). Forty rats were divided into negative (NC) and positive (PC) controls, OM, VD, and OM + VD groups, and MAFLD was induced by high-fat/high-fructose diet (12 weeks). Oral OM (415 mg/kg/day) and/or intramuscular VD (290 IU/kg/day) were given for 4 weeks (5 times/week). The PC animals were markedly obese and had hyperglycemia, insulin resistance, dyslipidemia, elevated liver enzymes, abnormal hepatic histology, and increased caspase-3 with apoptosis than the NC group. The expression of hepatic peroxisome proliferator-activated receptor-α (PPAR-α; 5.3-fold), insulin induced gene-1 (INSIG1; 7.8-fold), adiponectin receptor-1 (AdipoR1; 4.4-fold), and leptin receptor (LEPR; 6-fold) declined, while PPAR-γ (3.7-fold) and sterol regulatory element-binding protein-1 (SREBP1; 2.4-fold) increased, in the PC than the NC group. Leptin (2.2-fold), malondialdehyde (2.1-fold), protein carbonyl groups (17.3-fold), IL-1β (4.4-fold), IL-6 (2.1-fold), TNF-α (1.8-fold) also increased, whereas adiponectin (2.8-fold) glutathione (2.1-fold), glutathione peroxidase-1 (2.4-fold), glutathione reductase (2.2-fold), catalase (1.4-fold), and IL-10 (2.8-fold) decreased, in the PC livers. Both monotherapies attenuated obesity, metabolic profiles, and PPAR-γ/SREBP1/leptin/Caspase-3/apoptosis, while induced PPAR-α/adiponectin/AdipoR1/LEPR/INSIG1. The monotherapies also reduced the oxidative stress and pro-inflammatory markers and increased the antioxidant and anti-inflammatory molecules. However, the OM effects were better than VD monotherapy. Alternatively, the co-therapy group showed the greatest ameliorations in liver functions, lipid-regulatory molecules, oxidative stress, inflammation, and apoptosis. In conclusion, while OM monotherapy was superior to VD, the co-therapy protocol displayed the best alleviations against MAFLD, possibly by enhanced modulation of metabolic, antioxidant, and anti-inflammatory pathways.
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Affiliation(s)
- Bassem Refaat
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | | | - Jawwad Ahmad
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Osama M Abdalla
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Gehad E Elshopakey
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Shakir Idris
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Mohamed El-Boshy
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
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Lin YP, Wang PM, Chuang CH, Yong CC, Liu YW, Huang PY, Yao CC, Tsai MC. Metabolic Risks Are Increasing in Non-B Non-C Early-Stage Hepatocellular Carcinoma: A 10-Year Follow-Up Study. Front Oncol 2022; 12:816472. [PMID: 35186751 PMCID: PMC8848276 DOI: 10.3389/fonc.2022.816472] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 01/11/2022] [Indexed: 12/11/2022] Open
Abstract
Background Non-B, non-C hepatocellular carcinoma (NBNC-HCC) may be related to metabolic syndrome, and the incidence of this tumor type is increasing annually. The definition of metabolic-associated fatty liver disease (MAFLD) proposed in 2020 may help to more accuratelyassess the association between metabolic syndrome and NBNC-HCC. However, this new concept has not yet been applied in NBNC-HCC research. Therefore, this study aimed to compare the clinicopathological characteristics of patients with NBNC-HCC and CHB-HCC diagnosed between 2009-13 and 2014-18, focusing on metabolic risk factors and the new concept of MAFLD. Method Patients with BCLC-0/A-HCC who received curative hepatectomy between January 2009 and December 2018 were retrospectively assessed; the associations between clinicopathological characteristics and clinical outcomes of NBNC-HCC and CHB-HCC were analyzed by multivariate analysis. Result Compared to patients diagnosed in 2009-13, the frequency of metabolic disorders in NBNC-HCC was significantly higher in 2014-18 [DM (p=0.049), HTN (p=0.004), BMI (p=0.017) and MAFLD (p=0.003)]; there was no significant change in patients with CHB-HCC. Moreover, CHB-HCC was an independent risk factor for HCC recurrence (HR, 1.339; 95% CI, 1.010-1.775, p=0.043) and death (HR, 1.700; 95% CI, 1.017-2.842, p=0.043) compared to NBNC-HCC. Conclusions Therisk of MAFLD, obesity, DM, and hypertension in patients with early-stage NBNC have significantly increased in recent years, thus metabolic syndrome should be monitored in this special population. Moreover, NBNC-HCC tend to had a better prognosis than CHB-HCC, probably due to their distinct clinicopathological features.
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Affiliation(s)
- Yen-Po Lin
- School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
| | - Pei-Ming Wang
- Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | | | - Chee-Chen Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Pao-Yuan Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Ayada I, van Kleef LA, Alferink LJM, Li P, de Knegt RJ, Pan Q. Systematically comparing epidemiological and clinical features of MAFLD and NAFLD by meta-analysis: Focusing on the non-overlap groups. Liver Int 2022; 42:277-287. [PMID: 34953098 DOI: 10.1111/liv.15139] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 11/23/2021] [Accepted: 11/27/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS The applicability of the novel metabolic dysfunction associated fatty liver disease (MAFLD) definition has been studied in numerous cohorts and compared to non-alcoholic fatty liver disease (NAFLD). No consensus has been reached on which definition is preferred. Therefore, this meta-analysis aims to compare the epidemiological and clinical features of NAFLD and MAFLD in the general and non-general population. METHODS We searched Medline, Embase and Web of Science for studies comparing MAFLD to NAFLD. Based on MAFLD and NAFLD status, the following subgroups were investigated for liver health: overlap fatty liver disease (FLD), NAFLD-only and MAFLD-only. Data were pooled using random-effects models. RESULTS We included 17 studies comprising 9 808 677 individuals. In the general population, MAFLD was present in 33.0% (95% CI 29.7%-36.5%) and NAFLD in 29.1% (95% CI 27.1%-31.1%). Among those with FLD, 4.0% (95% CI 2.4%-6.4%) did not meet the MAFLD criteria but had NAFLD (NAFLD-only) and 15.1% (95% CI 11.5%-19.5%) was exclusively captured by the novel MAFLD definition (MAFLD-only). Notably, this MAFLD-only group was at significantly increased risk for fibrosis (RR 4.2; 95% CI 1.3-12.9) and had higher alanine aminotransferase (mean difference: 8.0 U/L, 95% CI 2.6-13.5) and aspartate aminotransferase (mean difference: 6.4 U/L, 95% CI 3.0-9.7), compared to NAFLD-only. Similar results were obtained among the non-general population. CONCLUSIONS Metabolic dysfunction associated fatty liver disease and NAFLD are highly prevalent in the general population, with considerable overlap between them. However, compared to NAFLD, significantly more individuals were additionally identified by MAFLD than were missed. Importantly, by using the MAFLD criteria, more individuals with liver damage were identified. Therefore, the novel MAFLD definition is superior to NAFLD on a population level.
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Affiliation(s)
- Ibrahim Ayada
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Laurens A van Kleef
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Louise J M Alferink
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Pengfei Li
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
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36
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Zheng Q, Nguyen MH. Letter: hepatic steatosis and fibrosis in chronic hepatitis B-the chicken-and-egg conundrum. Authors' reply. Aliment Pharmacol Ther 2022; 55:145-146. [PMID: 34907551 DOI: 10.1111/apt.16698] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Qi Zheng
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA.,Department of Hepatology, Hepatology Research institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
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37
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Liang Y, Chen H, Liu Y, Hou X, Wei L, Bao Y, Yang C, Zong G, Wu J, Jia W. Association of MAFLD With Diabetes, Chronic Kidney Disease, and Cardiovascular Disease: A 4.6-Year Cohort Study in China. J Clin Endocrinol Metab 2022; 107:88-97. [PMID: 34508601 PMCID: PMC8684479 DOI: 10.1210/clinem/dgab641] [Citation(s) in RCA: 131] [Impact Index Per Article: 43.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Indexed: 12/24/2022]
Abstract
CONTEXT In 2020, the terminology of metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). OBJECTIVES This work aimed to investigate the prevalence and incidence of MAFLD and evaluate its effects on incident extrahepatic diseases. METHODS A total of 6873 individuals, with a 4.6-year follow-up, were included in this study. Associations of MAFLD and NAFLD with diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD) were examined using logistic regression and Cox proportional hazards models. RESULTS The prevalence of NAFLD and MAFLD was 40.3% (95% CI, 39.2%-41.5%) and 46.7% (95% CI, 45.6%-47.9%), respectively. Additionally, 321 (4.7%) and 156 (2.3%) participants had MAFLD with excessive alcohol consumption and hepatitis B virus (HBV) infection. During the follow-up period, the incidence of NAFLD and MAFLD was 22.7% (95% CI, 21.3%-24.0%) and 27.0% (95% CI, 25.5%-28.4%). MAFLD was associated with higher risks of incident diabetes (risk ratio [RR] 2.08; 95% CI, 1.72-2.52), CKD (RR 1.64; 95% CI, 1.39-1.94), and CVD (hazard ratio 1.44; 95% CI, 1.15-1.81). Similar associations for NAFLD were observed. Furthermore, the MAFLD subgroups with excessive alcohol consumption (RR 2.49; 95% CI, 1.64-3.78) and HBV infection (RR 1.98; 95% CI, 1.11-3.52) were associated with higher risks of incident diabetes. CONCLUSION The change from NAFLD to MAFLD did not greatly affect the associations with diabetes, CKD, and CVD. MAFLD further identified those patients of metabolically fatty liver combined with excessive alcohol consumption and HBV infection, who had increased risks of incident diabetes compared with those of non-fatty liver.
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Affiliation(s)
- Yebei Liang
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Hongli Chen
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Yuexing Liu
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Xuhong Hou
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Li Wei
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Yuqian Bao
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Chunguang Yang
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
| | - Geng Zong
- Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China
| | - Jiarui Wu
- CAS Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
| | - Weiping Jia
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai 200233, China
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38
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Huang SC, Kao JH. Letter: hepatic steatosis and fibrosis in chronic hepatitis B-the chicken-and-egg conundrum. Aliment Pharmacol Ther 2022; 55:143-144. [PMID: 34907555 DOI: 10.1111/apt.16678] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Shang-Chin Huang
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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39
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Mantovani A. MAFLD vs NAFLD: Where are we? Dig Liver Dis 2021; 53:1368-1372. [PMID: 34108096 DOI: 10.1016/j.dld.2021.05.014] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/13/2021] [Accepted: 05/14/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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40
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Lin YP, Lin SH, Wang CC, Lin CC, Chen DW, Chuang CH, Huang PY, Hung CH, Yang SY, Cho WR, Chen YS, Tsai MC. Impact of MAFLD on HBV-Related Stage 0/A Hepatocellular Carcinoma after Curative Resection. J Pers Med 2021; 11:jpm11080684. [PMID: 34442328 PMCID: PMC8398387 DOI: 10.3390/jpm11080684] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 07/15/2021] [Accepted: 07/19/2021] [Indexed: 12/16/2022] Open
Abstract
Backgrounds and Aim: Metabolic-associated fatty liver dis-ease (MAFLD) is a novel term proposed in 2020 to avoid the exclusion of certain subpopulations, though the application of this term in the real world is very limited. Here, we aimed to evaluate the impact of MAFLD on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. Methods: Patients with chronic hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and December 2019 were consecutively selected. The association between histologically proven concurrent MAFLD and clinical outcomes were retrospectively analyzed. Results: Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients (37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver transplantation. Although no differences in the incidences of HCC recurrence (HR: 0.902, 95% CI: 0.719–1.131, p = 0.370) and death or liver transplantation (HR: 0.743, 95% CI: 0.518–1.006, p = 0.107) were observed between patients with and without MAFLD in multivariate analysis, the patients with MAFLD tended to achieve better recurrent-free survival compared to patients without MAFLD. Notably, lean MAFLD (BMI < 23 kg/m2) was a relative risk factor for tumor recurrence (HR: 2.030, 95% CI: 1.117–3.690, p = 0.020) among patients with MAFLD. Conclusions: The overall prognosis in HBV-related early-stage HCC, in terms of HCC recurrence and death or liver transplantation, was not significantly different between patients with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for HCC recurrence. Further studies are warranted to validate these results.
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Affiliation(s)
- Yen-Po Lin
- School of medicine, Chung-Shan Medical University, Taichung 40201, Taiwan; (Y.-P.L.); (Y.-S.C.)
| | - Shu-Hsien Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (S.-H.L.); (P.-Y.H.); (C.-H.H.); (S.-Y.Y.); (W.-R.C.)
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-C.W.); (C.-C.L.)
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (C.-C.W.); (C.-C.L.)
| | - Ding-Wei Chen
- Center for Translational Research in Biomedical Sciences, Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;
| | - Ching-Hui Chuang
- Department of Nursing, Meiho University, Pingtung 91202, Taiwan;
| | - Pao-Yuan Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (S.-H.L.); (P.-Y.H.); (C.-H.H.); (S.-Y.Y.); (W.-R.C.)
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (S.-H.L.); (P.-Y.H.); (C.-H.H.); (S.-Y.Y.); (W.-R.C.)
| | - Shih-Yu Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (S.-H.L.); (P.-Y.H.); (C.-H.H.); (S.-Y.Y.); (W.-R.C.)
| | - Wei-Ru Cho
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; (S.-H.L.); (P.-Y.H.); (C.-H.H.); (S.-Y.Y.); (W.-R.C.)
| | - Yu-Syuan Chen
- School of medicine, Chung-Shan Medical University, Taichung 40201, Taiwan; (Y.-P.L.); (Y.-S.C.)
| | - Ming-Chao Tsai
- School of medicine, Chung-Shan Medical University, Taichung 40201, Taiwan; (Y.-P.L.); (Y.-S.C.)
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
- Correspondence:
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41
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Mantovani A, Valenti L. A call to action for fatty liver disease. Liver Int 2021; 41:1182-1185. [PMID: 34002475 DOI: 10.1111/liv.14907] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 04/08/2021] [Indexed: 02/13/2023]
Affiliation(s)
- Alessandro Mantovani
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Hospital of Verona, Verona, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Precision Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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42
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Kang SH, Cho Y, Jeong SW, Kim SU, Lee JW, On behalf of Korean NAFLD Study Group. From nonalcoholic fatty liver disease to metabolic-associated fatty liver disease: Big wave or ripple? Clin Mol Hepatol 2021; 27:257-269. [PMID: 33751877 PMCID: PMC8046627 DOI: 10.3350/cmh.2021.0067] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/17/2021] [Accepted: 03/22/2021] [Indexed: 12/11/2022] Open
Abstract
There is some dissatisfaction with the term "nonalcoholic fatty liver disease (NAFLD)," which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended "metabolic (dysfunction)-associated fatty liver disease (MAFLD)" as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.
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Affiliation(s)
- Seong Hee Kang
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yuri Cho
- Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jin-Woo Lee
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - On behalf of Korean NAFLD Study Group
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
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Cao W, Xu Y, Shen Y, Wang Y, Ma X, Bao Y. Serum Fibroblast Growth Factor 23 Level and Liver Fat Content in MAFLD: A Community-Based Cohort. Diabetes Metab Syndr Obes 2021; 14:4135-4143. [PMID: 34616166 PMCID: PMC8487847 DOI: 10.2147/dmso.s328206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/16/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Although fibroblast growth factor-23 (FGF23) is involved in the development of metabolic diseases, its association with metabolic-associated fatty liver disease (MAFLD) remains unknown. We explored the relationship between serum fibroblast growth factor-23 level, metabolic associated fatty liver disease, and liver fat content. PATIENTS AND METHODS Participants were enrolled from communities in Shanghai. Serum fibroblast growth factor-23 level was determined using two-side sandwich enzyme-linked immunosorbent assays. MAFLD was diagnosed using the international expert consensus (2020) criteria. Liver fat content was assessed using ultrasound. RESULTS We enrolled 1827 individuals aged 30-80 years (mean age, 59.4±7.3 years). MAFLD was diagnosed in 445/1393 (31.9%) non-diabetic participants and 245/434 (56.5%) diabetic participants. After adjusting for confounders, one standard deviation increase in serum FGF23 was associated with MAFLD in diabetic (odds ratio, 1.27; 95% confidence interval, 1.15-1.49; P<0.001) and non-diabetic (odds ratio, 1.28; 95% confidence interval, 1.07-1.74; P=0.030) groups. In a fully adjusted linear regression model, serum FGF23 emerged as a positive determinant of liver fat content in both diabetic and non-diabetic groups (P=0.039; P=0.034). CONCLUSION Participants with MAFLD had higher serum fibroblast growth factor-23 level than those without MAFLD, regardless of diabetes status. Serum fibroblast growth factor-23 was independently related to MAFLD and liver fat content.
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Affiliation(s)
- Weijie Cao
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China
| | - Yiting Xu
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China
| | - Yun Shen
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China
| | - Yufei Wang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China
| | - Xiaojing Ma
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China
- Correspondence: Xiaojing Ma; Yuqian Bao Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of ChinaTel +86-21-64369181Fax +86-21-64368031 Email ;
| | - Yuqian Bao
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Shanghai Clinical Center for Diabetes; Shanghai Key Clinical Center for Metabolic Disease; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China
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