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Liu W, Sun X. Does metabolic dysfunction-associated fatty liver disease increase the risk of chronic kidney disease? A meta-analysis of cohort studies. BMC Nephrol 2024; 25:467. [PMID: 39707262 PMCID: PMC11661317 DOI: 10.1186/s12882-024-03910-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 12/09/2024] [Indexed: 12/23/2024] Open
Abstract
OBJECTIVE Metabolic dysfunction-associated fatty liver disease (MAFLD) has been used to characterize patients with fatty liver and metabolic dysfunction. The association between MAFLD and chronic kidney disease (CKD) remains undefined. We present high-quality evidence obtained from cohort studies examining if MAFLD leads to an increased risk of CKD. METHODS PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched from the earliest possible date to 17th May 2024 for cohort studies examining the link between MAFLD and CKD. RESULTS Eight studies with nine cohorts were included. Pooled analysis of all nine cohorts showed that MAFLD was an independent predictor of CKD (HR: 1.38 95% CI: 1.24, 1.53 I2 = 95%). No change in results was noted on sensitivity analysis. We also noted no change in the significance of effect size on subgroup analysis based on study design (prospective or retrospective), country of origin (China, Korea, Japan, or UK), the incidence of CKD in the cohort (> 10% or ≤ 10%) and if the study adjusted for cardiovascular disease, diabetes, hypertension, and smoking status. Further, meta-analysis showed that MAFLD was still a risk factor for CKD in men (HR: 1.38 95% CI: 1.22, 1.56 I2 = 86%), women (HR: 1.51 95% CI: 1.25, 1.82 I2 = 87%), overweight (HR: 1.41 95% CI: 1.20, 1.66 I2 = 89%) and non-overweight cohorts (HR: 1.35 95% CI: 1.20, 1.53 I2 = 9%). CONCLUSION MAFLD is an independent predictor of CKD. The association seems persistent irrespective of sex, body mass index, and other CKD risk factors.
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Affiliation(s)
- Wanghao Liu
- Department of Endocrinology, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, 2088 Tiaoxi East Road, Wuxing District, Huzhou City, Zhejiang Province, China
| | - Xiaoying Sun
- Department of Endocrinology, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, 2088 Tiaoxi East Road, Wuxing District, Huzhou City, Zhejiang Province, China.
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Yi J, Guo H, Jiang C, Duan J, Xue J, Zhao Y, He W, Xia L. Leukocyte telomere length decreased the risk of mortality in patients with alcohol-associated liver disease. Front Endocrinol (Lausanne) 2024; 15:1462591. [PMID: 39735642 PMCID: PMC11672197 DOI: 10.3389/fendo.2024.1462591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 11/12/2024] [Indexed: 12/31/2024] Open
Abstract
Background It is necessary to find latent indicators to predict the survival of alcohol-associated liver disease (ALD) patients. Leukocyte telomere length (LTL) was regarded as an indicator of prognosis in several diseases. However, the relationships between LTL and survival as well as cause-specific mortality in ALD patients were still unknown. Objective This study aimed at exploring the underlying link between LTL and the risk of mortality in patients with ALD. Methods The LTL and survival data were gathered from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The connection between LTL and mortality was assessed by Cox regression models and stratified analyses. The non-linear relationship was explored by restricted cubic spline (RCS) analysis. Sensitivity analyses were used to evaluate the robustness of our findings. Results LTL was a negative factor for all-cause mortality (all p-value < 0.05). The risk of cardiovascular disease (CVD)-related death was decreased in Q3 (p < 0.001) and Q4 levels of LTL (p < 0.001) compared with the Q1 group. Shorter LTL resulted in higher cancer-caused mortality (p = 0.03) in the Q2 group. Longer LTL improved survival especially for elder patients (p for trend < 0.001) or men (p for trend = 0.001). Moreover, there were L-shaped correlations between LTL and all-cause mortality (p for non-linearity = 0.02), as well as cancer-related mortality (p for non-linearity < 0.001). Four sensitivity analyses proved the robustness of our findings. Conclusion Our research found that longer LTL improved survival in patients with ALD and decreased CVD and cancer-related mortality. LTL decreased all-cause mortality especially for patients older than 65 years or men. LTL might be a useful biomarker for prognosis among patients with ALD. More prospective studies are needed to assess the relevance between LTL and mortality and explore the underlying mechanisms between them.
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Affiliation(s)
- Jiahong Yi
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Hui Guo
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chang Jiang
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Junyi Duan
- Department of Obstetrics and Gynecology, Zhuhai People’s Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, China
| | - Ju Xue
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yue Zhao
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wenzhuo He
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Liangping Xia
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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Pan J, Wu F, Chen M, He J, Gu Y, Pei L, Lai X, Zhang Z, Yang L. Prevalence of NAFLD, MAFLD, and MASLD: NHANES 1999-2018. DIABETES & METABOLISM 2024; 50:101562. [PMID: 38981569 DOI: 10.1016/j.diabet.2024.101562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 06/23/2024] [Accepted: 07/02/2024] [Indexed: 07/11/2024]
Affiliation(s)
- Jie Pan
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Feilong Wu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Mingtao Chen
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jinsen He
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China; Chancheng District Center for Disease Control and Prevention, Foshan, China
| | - Yingying Gu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Lei Pei
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Xuye Lai
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zhenfeng Zhang
- Department of Radiology, Translational Medicine Center, Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy & Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, Central Laboratory, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Lili Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.
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Kang MK, Song JE, Kweon YO, Tak WY, Park SY, Lee YR, Park JG. Visceral Obesity and Its Association with Severe Coronary Artery Calcification in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. Diagnostics (Basel) 2024; 14:2305. [PMID: 39451628 PMCID: PMC11506773 DOI: 10.3390/diagnostics14202305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open
Abstract
Background/Objectives: The role of body composition parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with presence and severity of coronary artery calcification (CAC) is still not fully elucidated. We aimed to evaluate the impact of computed tomography (CT)-based body composition parameters in patients with MASLD with CAC severity. Methods: In this multicenter study, 1870 individuals underwent cardiac CT for the detection of CAC as well as ultrasonography for the diagnosis of hepatic steatosis. The presence of CAC was defined by a CAC score threshold of >0, while severe CAC was defined by a threshold of >300. Using the abdominal cross-sectional CT images at the L3 vertebra level, we analyzed the skeletal muscle index, visceral to subcutaneous adipose tissue ratio, and muscle density using the Hounsfield unit. Results: Of 648 patients with MASLD, the proportions of presence of CAC and severe CAC were 45.2% and 9.9%, respectively. Visceral obesity was not associated with the presence of CAC after adjustment for age, sex, smoking, statin therapy, type 2 diabetes, and advanced fibrosis (adjusted odds ratio (aOR), 1.38; 95% confidence interval (CI), 0.86-2.23; p = 0.180). However, visceral obesity was independently associated with severe CAC after adjustment for several metabolic risk factors (aOR, 3.54; 95% CI, 1.25-14.90; p = 0.039), and adjustment for atherosclerotic cardiovascular disease risk scores (aOR, 3.74; 95% CI, 1.31-15.79; p = 0.032). Conclusions: Visceral obesity may serve as a novel prognostic CT-based radiological biomarker for patients with MASLD with severe CAC.
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Affiliation(s)
- Min Kyu Kang
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea;
| | - Jeung Eun Song
- Department of Internal Medicine, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea;
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Jung Gil Park
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea;
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Kang MK, Song JE, Loomba R, Park SY, Tak WY, Kweon YO, Lee YR, Park JG. Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification. Sci Rep 2024; 14:22917. [PMID: 39358447 PMCID: PMC11447001 DOI: 10.1038/s41598-024-74287-7] [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: 02/22/2024] [Accepted: 09/25/2024] [Indexed: 10/04/2024] Open
Abstract
We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.
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Affiliation(s)
- Min Kyu Kang
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, South Korea
- MASLD Research Centre, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, La Jolla, San Diego, CA, USA
| | - Jeong Eun Song
- Department of Internal Medicine, School of Medicine, Daegu Catholic University, Daegu, South Korea
| | - Rohit Loomba
- MASLD Research Centre, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, La Jolla, San Diego, CA, USA
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
| | - Jung Gil Park
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, South Korea.
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Zhou XD, Targher G, Byrne CD, Shapiro MD, Chen LL, Zheng MH. Metabolic dysfunction-associated fatty liver disease: bridging cardiology and hepatology. CARDIOLOGY PLUS 2024; 9:275-282. [DOI: 10.1097/cp9.0000000000000106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases, affecting approximately 30% of the global adult population, with a rise largely attributed to increasing rates of obesity and diabetes worldwide. Historically, the term “NAFLD” did not explicitly link the condition to its most common causes, such as obesity and diabetes, or its principal pathophysiological mechanisms, including insulin resistance and low-grade chronic metabolic inflammation. This semantic laxity has potentially reduced attempts at screening, diagnosis, and management. The shift to using the terms metabolic-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a more accurate understanding of the condition’s metabolic origins and highlights its broader implications, particularly its link to cardiovascular diseases. MAFLD/MASLD represents a convergence point between hepatology and cardiology, with metabolic dysfunction serving as the bridge between liver pathology and increased cardiovascular risk. Growing clinical evidence reveals a strong association between MAFLD/MASLD and cardiovascular morbidity and mortality. Despite this, cardiovascular risks associated with MAFLD/MASLD are often underestimated, especially among cardiologists. This narrative review explores the potential clinical implications of MAFLD/MASLD for cardiology practice, examining diagnostic criteria, cardiovascular risk assessment, adjustments in clinical practice, collaborative care strategies, treatment options, and directions for future research.
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Affiliation(s)
- Xiao-Dong Zhou
- Department of Cardiovascular Medicine, the Heart Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325030, China
| | - Giovanni Targher
- Department of Medicine, University of Verona, Verona 37024, Italy
- Metabolic Diseases Research Unit, IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella 37024, Italy
| | - Christopher D. Byrne
- Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton, and University of Southampton, Southampton General Hospital, Southampton SO17 1BJ, UK
| | - Michael D. Shapiro
- Center for Prevention of Cardiovascular Disease, Section on Cardiovascular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27130, USA
| | - Li-Li Chen
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325030, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325030, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou 325030, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou 325030, China
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Kim GA, Jeong S, Jang H, Lee DH, Joo SK, Kim W. Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease with Increased Alcohol Intake Increase the Risk of Developing Hepatocellular Carcinoma and Incident or Decompensated Cirrhosis: A Korean Nationwide Study. Liver Cancer 2024; 13:426-437. [PMID: 39114758 PMCID: PMC11305668 DOI: 10.1159/000535943] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 12/19/2023] [Indexed: 08/10/2024] Open
Abstract
Introduction This study aimed to investigate the liver-related outcomes of newly suggested metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD), as well as alcohol-associated liver disease (ALD). Methods From a National Health Insurance Service Health Screening Cohort, we included 369,094 participants who underwent health checkups between 2009 and 2010 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥60. The risk of primary liver cancer (PLCa), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), incident cirrhosis, and decompensated cirrhosis was compared with no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model regarding competing risks. Results A total of 3,232 participants (0.9%) developed PLCa during the median follow-up of 3,227,176 person-years: 0.5% with no SLD, 1.1% with MASLD, 1.3% with MetALD, and 1.9% with ALD. Competing risk analysis revealed that compared with no SLD, MASLD (SHR: 1.65; 95% CI: 1.44-1.88), MetALD (SHR: 1.87; 95% CI: 1.52-2.29), and ALD (SHR: 1.86; 95% CI: 1.39-2.49) were associated with an increased risk of PLCa. MASLD (SHR: 1.96; 95% CI: 1.67-2.31), MetALD (SHR: 2.23; 95% CI: 1.75-2.84), and ALD (SHR: 2.34; 95% CI: 1.67-3.29) were associated with a higher risk of HCC. No significant difference was observed in the risk of iCCA. The risk of incident cirrhosis and decompensated cirrhosis increased in the order of no SLD, MASLD, MetALD, and ALD. Conclusion MASLD, MetALD, and ALD have an increased risk of PLCa, HCC, incident cirrhosis, and decompensated cirrhosis but not iCCA. These findings may serve as a robust ground for the prognostic value of the newly suggested MASLD and MetALD.
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Affiliation(s)
- Gi-Ae Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, South Korea
| | - Seogsong Jeong
- Department of Medical Informatics, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Heejoon Jang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea
| | - Dong Hyeon Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea
| | - Sae Kyung Joo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea
| | - Won Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea
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Lee Y, Cho EJ, Choe EK, Kwak MS, Yang JI, Oh SW, Yim JY, Chung GE. Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population. Sci Rep 2024; 14:9753. [PMID: 38679617 PMCID: PMC11056367 DOI: 10.1038/s41598-024-60152-0] [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: 07/14/2023] [Accepted: 04/19/2024] [Indexed: 05/01/2024] Open
Abstract
Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10-15 and 4.84 × 10-10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10-4, and 7.15 × 10-4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10-8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43 × 10-12 and MD-MAFLD: 1.300 (1.191-1.416), 2.90 × 10-9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10-8 and 1.225 (1.122, 1.340), 7.06 × 10-6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.
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Affiliation(s)
- Young Lee
- Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea
- Department of Applied Statistics, Chung-Ang University, Seoul, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Eun Kyung Choe
- Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Min-Sun Kwak
- Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Jong In Yang
- Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Seung-Won Oh
- Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
- Department of Family Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong Yoon Yim
- Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Goh Eun Chung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Department of Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
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Kang MK, Song J, Loomba R, Park S, Tak W, Kweon Y, Lee Y, Park JG. Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification. RESEARCH SQUARE 2024:rs.3.rs-3979461. [PMID: 38496485 PMCID: PMC10942572 DOI: 10.21203/rs.3.rs-3979461/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of >0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR, 1.20; 95% CI, 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR, 1.38; 95% CI, 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR, 1.22; 95% CI, 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.
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Affiliation(s)
| | | | | | | | - Won Tak
- Kyungpook National University
| | | | - Yu Lee
- Kyungpook National University
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10
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Wang TJ, Chen MY, Lin YC, Chiu WN, Huang TJ, Weng HH. High prevalence of fatty liver and its association with metabolic syndrome among rural adults with chronic hepatitis C: Implications for primary healthcare. BMC Public Health 2024; 24:532. [PMID: 38378519 PMCID: PMC10880326 DOI: 10.1186/s12889-024-17851-0] [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: 02/11/2023] [Accepted: 01/23/2024] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Chronic hepatitis C (CHC) virus infection is a global health concern that is associated with significant liver-related morbidity and mortality. Owing to the inflammatory pathway, CHC can causefatty liver, liver cirrhosis, and liver cancer and is associated with cardiometabolic diseases, such as hypertension and diabetes. Fatty liver is associated with metabolic disorders, cardiovascular diseases, diabetes, and liver cancer. Hence, the early detection of fatty liver through noninvasive screening in adults with CHC is important in primary healthcare settings. This study aimed to explore the prevalence of fatty liver and its association with metabolic syndrome amongrural adults with CHC. METHODS This was a series of cohort studies related to the elimination of the CHC burden around the western coastal Yunlin County, Taiwan, between August 2018 and July 2021. A cross-sectional study was conducted after hepatitis C virus RNA confirmation in a hepatitis C- endemic area. A gastrointestinal physician or radiologist assessed fatty liver by ultrasonography. Fatty liver was classified into four grades: normal, mild, moderate, and severe. Three liver enzyme biomarkers were identified. According to the Taiwan national standard, metabolic syndrome was defined based on the presence of three or more of the five abnormal biomarkers, including increased waist circumference, elevated blood pressure, elevated fasting blood glucose level, elevated triglyceride level, and low high-density lipoprotein cholesterol level. RESULTS A total of 256 rural adults with CHC were enrolled. The mean age of the participants was 67.5 (standard deviation = 11.8) years, with a low educational level. High prevalence of fatty liver (79%), central obesity (54.3%), elevated blood pressure (55.5%),elevated fasting blood glucose (FBG) level (44.9%), and metabolic syndrome (37.9%) were observed.The results showed that adults with CHC with moderate to severe fatty liver were significantly associated with an increased risk of increased waist circumference (P < 0.001), increased blood pressure (P < 0.001), low high-density lipoprotein cholesterol level (P < 0.05), and elevated liver enzyme biomarker levels (all P < 0.05) after adjusting for age, sex, and educational level. Furthermore, adults with CHC with moderate to severe fatty liver were significantly associated with a greater risk of metabolic syndrome (odds ratio = 2.85, 95% confidence interval = 1.66 to 4.92). CONCLUSIONS The findings demonstrate a high prevalence of fatty liver in rural adults with CHC, which is significantly associated with obesity, metabolic syndrome, and elevated liver biomarker levels. Clinicians and primary healthcare providers must encourage patients with CHC to receive antiviral therapy combined with weight loss management and lifestyle modification, allowing general improvements in their liver and cardiometabolic health.
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Affiliation(s)
- Ta-Jen Wang
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Mei-Yen Chen
- Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- School of Nursing, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Chih Lin
- Department of Family Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Wen-Nan Chiu
- Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Tung-Jung Huang
- Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - Hsu-Huei Weng
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
- Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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11
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Fernandez CJ, Alkhalifah M, Afsar H, Pappachan JM. Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink. Pathogens 2024; 13:68. [PMID: 38251375 PMCID: PMC10821334 DOI: 10.3390/pathogens13010068] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/05/2024] [Accepted: 01/07/2024] [Indexed: 01/23/2024] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease.
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Affiliation(s)
- Cornelius J. Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, UK;
| | - Mohammed Alkhalifah
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia
| | - Hafsa Afsar
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
| | - Joseph M. Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PL, UK
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12
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Di Bartolomeo A, George J. Future directions for fatty liver disease. METABOLIC STEATOTIC LIVER DISEASE 2024:297-317. [DOI: 10.1016/b978-0-323-99649-5.00016-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Seo SH, Cho KJ, Park HJ, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Cheon JH, Yook JI, Kim MD, Joo DJ, Kim SU. Inhibition of Dickkopf-1 enhances the anti-tumor efficacy of sorafenib via inhibition of the PI3K/Akt and Wnt/β-catenin pathways in hepatocellular carcinoma. Cell Commun Signal 2023; 21:339. [PMID: 38012711 PMCID: PMC10680194 DOI: 10.1186/s12964-023-01355-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 10/14/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Sorafenib improves the overall survival in patients with advanced hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) is commonly overexpressed in HCC. In this study, we investigated whether the inhibition of DKK1 enhances the anti-tumor efficacy of sorafenib in HCC. METHODS HCC cells were treated with sorafenib and WAY-262611, which is an inhibitor of DKK1. Transgenic mouse models were also developed using hydrodynamic tail vein injection. Mice were orally administered with sorafenib (32 mg/kg), WAY-262611 (16 mg/kg), or sorafenib + WAY-262611 for 10 days. Mechanisms of sorafenib and WAY-262611 were explored via western blotting, immunostaining, and RNA sequencing. RESULTS DKK1 was significantly overexpressed in patients with HCC than in the healthy controls and patients with liver diseases except HCC (all P < 0.05). Compared with sorafenib alone, sorafenib + WAY-262611 significantly inhibited the cell viability, invasion, migration, and colony formation by promoting apoptosis and altering the cell cycles in HCC cells (all P < 0.05). Moreover, sorafenib + WAY-262611 decreased the p110α, phospho-Akt (all P < 0.05), active β-catenin (all P < 0.05) and phospho-GSK-3β (Ser9) expression levels, while increasing the phospho-GSK-3β (Tyr216) expression levels compared with those in the sorafenib alone in vitro and in vivo. In addition, sorafenib + WAY-262611 inhibited tumor progression by regulating cell proliferation and apoptosis, significantly better than sorafenib alone in mouse models. CONCLUSIONS Our results indicate that DKK1 inhibition significantly enhances the anti-tumor efficacy of sorafenib by inhibiting the PI3K/Akt and Wnt/β-catenin pathways via regulation of GSK3β activity, suggesting a novel therapeutic strategy for HCC. Video Abstract.
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Affiliation(s)
- Sang Hyun Seo
- Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Kyung Joo Cho
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hye Jung Park
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hye Won Lee
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
| | - Beom Kyung Kim
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
| | - Jun Yong Park
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
| | - Do Young Kim
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
| | - Sang Hoon Ahn
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Jong In Yook
- Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea
| | - Man-Deuk Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University of College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Yonsei Liver Center, Severance Hospital, Seoul, Korea.
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea.
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14
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Xing M, Ni Y, Zhang Y, Zhao X, Yu X. The relationship between skeletal muscle mass to visceral fat area ratio and metabolic dysfunction-associated fatty liver disease subtypes in middle-aged and elderly population: a single-center retrospective study. Front Nutr 2023; 10:1246157. [PMID: 38024359 PMCID: PMC10663359 DOI: 10.3389/fnut.2023.1246157] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
Background It has been reported that decreased muscle mass combined with excessive visceral adipose tissue are significantly correlated with the risk of non-alcoholic fatty liver disease (NAFLD). However, it has not been explored among populations with metabolic dysfunction-associated fatty liver disease (MAFLD) subtypes. We aimed to investigate whether appendicular skeletal muscle mass to visceral fat area ratio (SVR), an indicator of sarcopenic obesity, influences on the risk of MAFLD subtypes and its hepatic condition in middle-aged and elderly population. Methods A total of 4,003 middle-aged and elderly subjects were finally enrolled in this single-center retrospective study. Abdominal ultrasonography was employed for hepatic steatosis diagnosis. Participants were divided into four groups: diabetes-MAFLD, overweight/obese-MAFLD, lean-MAFLD and no MAFLD. Appendicular skeletal muscle mass as well as visceral fat area (VAF) was estimated by bioimpedance analysis measurements. Liver fibrosis was defined as a Fibrosis-4 index (FIB-4) and the NAFLD Fibrosis Score (NFS). Multivariate logistic regression analysis was performed to estimate the odds ratio and 95% confidence interval between SVR and MAFLD subtypes/hepatic condition stratified by sex. Results Participants with MAFLD subtypes had a significant lower value of SVR compared with those without MAFLD (P<0.001), while high quartiles of FIB-4 and NFS also showed a decreasing value of SVR in comparison with its lower quartiles (Pfor trend<0.001). The lowest quartile of SVR increased the prevalence of MAFLD subtypes [adjusted OR (95%CI): 2.96 (1.48 ~ 5.93) male /3.30(1.46 ~ 7.46) female for diabetes-MAFLD, 1.91(1.26 ~ 2.88) male /4.48(1.91 ~ 10.49) female for overweight/obese-MAFLD and 4.01(1.46 ~ 10.98) male/2.53(1.19 ~ 5.37) female for lean-MAFLD groups] compared with the highest quartile of SVR (all Pfor trend<0.001). Besides, the interaction effect of gender on the relationship between SVR and MAFLD subtypes was statistically significant (all Pfor interaction<0.001).Restricted cubic spline indicated an inverse association between SVR and the risk of MAFLD subtypes with linearity (all P for non-linearity>0.05). The lowest quartile of SVR also increases the risk of MAFLD fibrosis in both males and females. Conclusion Our study concluded that a decrease in SVR (appendicular skeletal muscle mass divided by visceral fat area) is significantly associated with an increased prevalence of developing MAFLD subtypes and liver fibrosis in middle-aged and older persons of both genders.
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Affiliation(s)
- Mengchen Xing
- Department of Thyroid, Breast, and Gastrointestinal Surgery, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Yanlan Ni
- Department of Thyroid, Breast, and Gastrointestinal Surgery, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Ye Zhang
- Department of Minimally Invasive Laparoscopy, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Xiaoqian Zhao
- Emergency Intensive Care Unit, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Xin Yu
- Department of Hepatobiliary Surgery, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
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15
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Ramírez-Mejía MM, Qi X, Abenavoli L, Romero-Gómez M, Eslam M, Méndez-Sánchez N. Metabolic dysfunction: The silenced connection with fatty liver disease. Ann Hepatol 2023; 28:101138. [PMID: 37468095 DOI: 10.1016/j.aohep.2023.101138] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 07/21/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents a global public health burden. Despite the increase in its prevalence, the disease has not received sufficient attention compared to the associated diseases such as diabetes mellitus and obesity. In 2020 it was proposed to rename NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in order to recognize the metabolic risk factors and the complex pathophysiological mechanisms associated with its development. Furthermore, along with the implementation of the proposed diagnostic criteria, the aim is to address the whole clinical spectrum of the disease, regardless of BMI and the presence of other hepatic comorbidities. As would it be expected with such a paradigm shift, differing viewpoints have emerged regarding the benefits and disadvantages of renaming fatty liver disease. The following review aims to describe the way to the MAFLD from a historical, pathophysiological and clinical perspective in order to highlight why MAFLD is the approach to follow.
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Affiliation(s)
- Mariana M Ramírez-Mejía
- Plan of Combined Studies in Medicine (PECEM-MD/PhD), Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico; Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Liaoning Province, China
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Graecia of Catanzaro, Italy
| | - Manuel Romero-Gómez
- Digestive Diseases Unit, Department of Medicine, SeLiver Group, Institute of Biomedicine of Sevilla (HUVR/CSIC/US), University of Seville, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico; Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
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16
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Gong Y, Kang J, Wang X, Zheng Y, Sui Y, Lu W. Increased detection rates of advanced colorectal adenoma in women with metabolic dysfunction-associated fatty liver disease. Heliyon 2023; 9:e22391. [PMID: 38045162 PMCID: PMC10689946 DOI: 10.1016/j.heliyon.2023.e22391] [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: 04/27/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 12/05/2023] Open
Abstract
Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new concept with its own diagnostic criteria. There are few studies on its relationship with colorectal adenoma. Objective This study aimed to explore the relationship between MAFLD and colorectal adenoma and to compare the predictive value of MAFLD with other risk factors. Methods A total of 4436 consecutive physical examination subjects were enrolled. They all underwent colonoscopy and abdominal ultrasound. MAFLD was diagnosed by both fatty liver disease and metabolic dysfunction. The correlation between colorectal adenoma and MAFLD was studied using a logistic regression model. Results: The prevalence of MAFLD was 31.72 % (1407/4436). The adenoma detection rate in MAFLD patients was higher than that in controls (13.50 %, 190/1407 vs. 10.70 %, 324/3029, p < 0.001). Univariate analysis indicated that MAFLD individuals were 1.303-fold as likely to have colonic adenoma as controls [odds ratio (OR) 1.303 and 95 % confidence interval (CI), 1.076-1.578, p = 0.007]. Multivariate analysis showed that age, male sex, BMI and smoking were positively associated with the risk of colorectal adenoma, with OR values of 1.044 (95 % CI, 1.031 to 1.058), 1.720 (95 % CI, 1.221 to 2.424), 1.046 (95 % CI, 1.009 to 1.085) and 1.342 (95 % CI, 1.072 to 1.680), respectively. MAFLD in women, but not in men, had an independent relationship with increased detection of advanced adenoma (OR 3.932, 95 % CI, 1.023-15.1117, p = 0.046). Conclusion Individuals with MAFLD are more likely to develop colorectal adenoma than those without MAFLD. The influence of MAFLD on advanced colorectal adenoma was especially prominent in females.
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Affiliation(s)
- Yan Gong
- Department of Health Medicine, The Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, China
| | - Juan Kang
- Department of Emergency, The Second Medical Center & National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, China
| | - Xinyan Wang
- Chinese PLA Medical School, China
- China Unit 93658 of the PLA, No. 1, China
| | - Yansong Zheng
- Department of Health Medicine, The Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, China
| | - Ying Sui
- The 6th Health Department, Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Wenping Lu
- Faculty of Hepatopancreatobiliary Surgery, First Medical Center, Chinese PLA General Hospital, China
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17
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Cho Y, Chang Y, Ryu S, Wild SH, Byrne CD. Nonalcoholic fatty liver disease without overlapping metabolic-associated fatty liver disease and the risk of incident type 2 diabetes. Liver Int 2023; 43:2445-2454. [PMID: 37387519 DOI: 10.1111/liv.15661] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 06/14/2023] [Accepted: 06/15/2023] [Indexed: 07/01/2023]
Abstract
BACKGROUND AND AIMS Re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex. METHODS 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups. RESULTS A total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63-3.51) and 5.75 (5.17-6.36) (women), and 1.53 (1.25-1.88) and 2.60 (2.44-2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex <0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes). CONCLUSIONS NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.
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Affiliation(s)
- Yoosun Cho
- Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea
| | - Seungho Ryu
- Center for Cohort Studies, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea
| | - Sarah H Wild
- Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health and Care Research Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
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18
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Kim MN, Han K, Yoo J, Hwang SG, Zhang X, Ahn SH. Diabetic MAFLD is associated with increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis patients. Int J Cancer 2023; 153:1448-1458. [PMID: 37439276 DOI: 10.1002/ijc.34637] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 06/06/2023] [Accepted: 06/09/2023] [Indexed: 07/14/2023]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) can coexist with chronic viral hepatitis. MAFLD is a heterogeneous disease because the diagnostic criteria include various metabolic traits. We aimed to identify patients at high risk of poor long-term outcomes based on MAFLD subgroups in chronic viral hepatitis patients. We evaluated 63 273 chronic hepatitis B and C patients. Patient with a fatty liver index ≥30 was defined to have hepatic steatosis. MAFLD was defined as the presence of hepatic steatosis with any one of the following three conditions, overweight/obesity, type 2 diabetes or ≥2 metabolic risk factors. The prevalence of MAFLD was 38.4% (n = 24 290). During a median 8.8-year follow-up, 1839 HCCs and 2258 deaths were documented in MAFLD patients. Among MAFLD patients, diabetes could identify patients at high risk of HCC and mortality, whereas overweight/obesity and metabolic risk factors did not. Compared with non-MAFLD patients, risk of HCC and mortality was significantly higher in diabetic MAFLD patients (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] = 1.26-1.43 for HCC; aHR = 1.15, 95% CI = 1.08-1.22 for mortality). Risk of HCC and mortality was significantly higher in diabetic MAFLD patients (aHR = 1.40, 95% CI = 1.26-1.55 for HCC; aHR = 1.77, 95% CI = 1.63-1.93 for mortality) compared with non-diabetic MAFLD patients. Diabetic MAFLD is associated with increased risk of HCC and mortality among chronic viral hepatitis patients. Our findings highlight the need for close surveillance and effective treatment for these high-risk patients to reduce HCC and mortality in patients with chronic viral hepatitis.
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Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Juhwan Yoo
- Department of Biomedicine & Health Science, The Catholic University of Korea, Seoul, South Korea
| | - Seong Gyu Hwang
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
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19
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Kim GA, Moon JH, Kim W. Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity. Clin Mol Hepatol 2023; 29:831-843. [PMID: 37634892 PMCID: PMC10577343 DOI: 10.3350/cmh.2023.0277] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/12/2023] [Accepted: 08/23/2023] [Indexed: 08/29/2023] Open
Abstract
The existing term non-alcoholic fatty liver disease (NAFLD) has raised substantial concerns due to its inherent disadvantages of using exclusionary diagnostic criteria and the stigmatizing word 'fatty.' Three pan-national liver associations set out to explore a new nomenclature to replace both NAFLD and its suggested alternative, metabolic (dysfunction)-associated fatty liver disease (MAFLD). They surveyed if a change in nomenclature and/or definition is favored and which nomenclature best communicates disease characteristics and increases awareness. In lieu of NAFLD/MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD) has been chosen, and an umbrella term, steatotic liver disease (SLD), encompassing the whole spectrum of liver disease, has been proposed. It has been suggested that cardiometabolic risk factors should be considered when categorizing SLD patients. Furthermore, a new subcategory, MASLD with increased alcohol intake (MetALD), casts light on a neglected group of patients with moderate or more alcohol consumption. The importance of metabolic dysfunction was acknowledged in this new nomenclature, but the precise contribution of metabolic dysfunction and alcohol consumption to the development and progression of SLD remains unclear. Herein, we review hepatologists' and endocrinologists' perspectives on the new nomenclature, along with its possible impact on clinical practice. Although it is premature to predict the settlement of the new nomenclature, this review may help build more evidence for a soft landing of it in the future.
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Affiliation(s)
- Gi-Ae Kim
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Joon Ho Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea
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Cotrim HP. From Nonalcoholic Steatohepatits to Steatotic Liver Disease: A Long Way. Diagnostics (Basel) 2023; 13:3104. [PMID: 37835846 PMCID: PMC10572989 DOI: 10.3390/diagnostics13193104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 09/20/2023] [Accepted: 09/25/2023] [Indexed: 10/15/2023] Open
Abstract
In 1980, Ludwig et al [...].
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21
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Tao M, Liu J, Chen X, Wang Q, He M, Chen W, Wang C, Zhang L. Correlation between serum uric acid and body fat distribution in patients with MAFLD. BMC Endocr Disord 2023; 23:204. [PMID: 37749567 PMCID: PMC10518962 DOI: 10.1186/s12902-023-01447-7] [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: 03/22/2023] [Accepted: 08/31/2023] [Indexed: 09/27/2023] Open
Abstract
BACKGROUND Metabolic dysfunction associated with fatty liver disease (MAFLD) is often correlated with obesity and hyperuricemia. The present study aimed to determine the association between serum uric acid (SUA) and central fat distribution in patients with MAFLD. METHODS A total of 485 patients were classified into the following groups: (1) controls without MAFLD and hyperuricemia (HUA), (2) MAFLD with normal SUA, and (3) MAFLD with HUA. DUALSCAN HDS-2000 was used to measure visceral fat (VAT) and subcutaneous fat (SAT). Dual-energy X-ray absorptiometry (DEXA) was used to measure body fat distribution. RESULTS MAFLD patients with HUA had remarkably higher BMI, fasting insulin, OGIRT AUC, ALT, AST, TG, VAT, SAT, Adipo-IR, trunk fat mass, android fat, and total body fat than MAFLD patients with normal SUA (all p < 0.05). The increase in VAT, SAT, CAP, Adipo-IR, upper limbs fat mass, trunk fat mass, and android fat, as well as the percentage of MAFLD, were significantly correlated with the increase in SUA. The percentage of MAFLD patients with HUA increased significantly with increasing VAT or SAT, as determined by the Cochran-Armitage trend test (all p < 0.05). Furthermore, VAT (OR = 1.01 CI: 1.00, 1.03; p < 0.05) and adipo-IR (OR = 1.09 CI: 1.00, 1.19; p < 0.05) were associated with circling SUA in MAFLD after adjusting for sex, age, TG, TC, HOMA-IR, and BMI. CONCLUSION Abdominal fat promotes the co-existence of HUA and MAFLD, while weight loss, especially, decreasing VAT, is of great importance to decrease SUA levels and manage MAFLD.
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Affiliation(s)
- Min Tao
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Jing Liu
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Xingyu Chen
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Qing Wang
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Miao He
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Wenwen Chen
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
| | - Cong Wang
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
| | - Lili Zhang
- Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
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22
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Robea MA, Balmus IM, Girleanu I, Huiban L, Muzica C, Ciobica A, Stanciu C, Cimpoesu CD, Trifan A. Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease-Oxidative Stress and Inflammation Relevance. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1614. [PMID: 37763733 PMCID: PMC10535217 DOI: 10.3390/medicina59091614] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/29/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.
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Affiliation(s)
- Madalina Andreea Robea
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.R.); (I.-M.B.); (C.D.C.)
| | - Ioana-Miruna Balmus
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.R.); (I.-M.B.); (C.D.C.)
- Department of Exact Sciences and Natural Sciences, Institute of Interdisciplinary Research, “Alexandru Ioan Cuza” University of Iasi, Alexandru Lapusneanu Street, No. 26, 700057 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Alin Ciobica
- Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, No. 20A, 700505 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue, No. 8, 700506 Iasi, Romania;
- Academy of Romanian Scientists, Splaiul Independentei nr. 54, Sector 5, 050094 Bucuresti, Romania
| | - Carol Stanciu
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue, No. 8, 700506 Iasi, Romania;
| | - Carmen Diana Cimpoesu
- CENEMED Platform for Interdisciplinary Research, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (M.A.R.); (I.-M.B.); (C.D.C.)
- Department of Emergency Medicine, Emergency County Hospital “Sf. Spiridon”, 700111 Iasi, Romania
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa” Iasi, Blvd. Independentei 1, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.G.); (L.H.); (C.M.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
- Centre of Biomedical Research, Romanian Academy, Carol I Avenue, No. 8, 700506 Iasi, Romania;
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23
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Song BG, Choi SC, Goh MJ, Kang W, Sinn DH, Gwak GY, Paik YH, Choi MS, Lee JH, Paik SW. Metabolic dysfunction-associated fatty liver disease and the risk of hepatocellular carcinoma. JHEP Rep 2023; 5:100810. [PMID: 37538246 PMCID: PMC10393797 DOI: 10.1016/j.jhepr.2023.100810] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 03/23/2023] [Accepted: 05/18/2023] [Indexed: 08/05/2023] Open
Abstract
Background & Aims The metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. Methods A cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). Results Participants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92-1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09-3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01-2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. Conclusions In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. Impact and Implications This study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.
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Affiliation(s)
- Byeong Geun Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sung Chul Choi
- Center for Health Promotion, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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24
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Han E, Chun HS, Lee YH, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Lee BW, Kang ES, Cha BS, Ahn SH, Kim SU. MAFLD might be better in identifying subjects with sarcopenia or cardiovascular risk than NAFLD: A nationwide study. J Gastroenterol Hepatol 2023; 38:1598-1609. [PMID: 37321651 DOI: 10.1111/jgh.16261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 05/14/2023] [Accepted: 05/30/2023] [Indexed: 06/17/2023]
Abstract
BACKGROUND AND AIM Clinical features of non-alcoholic fatty liver disease (NAFLD), but not fulfilling the diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD), remain unclear. We investigated the risk of sarcopenia and cardiovascular disease (CVD) in MAFLD and non-metabolic risk (MR) NAFLD. METHODS Subjects were selected from the Korean National Health and Nutrition Examination Surveys 2008-2011. Liver steatosis was assessed using fatty liver index. Significant liver fibrosis was defined using fibrosis-4 index, categorized by age cut-offs. Sarcopenia was defined as the lowest quintile sarcopenia index. Atherosclerotic CVD (ASCVD) risk score > 10% was defined as high probability. RESULTS A total of 7248 subjects had fatty liver (137 with non-MR NAFLD, 1752 with MAFLD/non-NAFLD, and 5359 with overlapping MAFLD and NAFLD). In non-MR NAFLD group 28 (20.4%) had significant fibrosis. The risk of sarcopenia (adjusted odds ratio [aOR] = 2.71, 95% confidence index [CI] = 1.27-5.78) and high probability of ASCVD (aOR = 2.79, 95% CI = 1.23-6.35) was significantly higher in MAFLD/non-NAFLD group than in non-MR NAFLD group (all P < 0.05). The risk of sarcopenia and high probability of ASCVD was similar between subjects with and without significant fibrosis in non-MR NAFLD group (all P > 0.05). However, the risk was significantly higher in MAFLD group than in non-MR NAFLD group (aOR = 3.38 for sarcopenia and 3.73 for ASCVD; all P < 0.05). CONCLUSIONS The risks of sarcopenia and CVD were significantly higher in MAFLD group but did not differ according to fibrotic burden in non-MR NAFLD group. The MAFLD criteria might be better for identifying high-risk fatty liver disease than the NAFLD criteria.
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Affiliation(s)
- Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Yong-Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Byung-Wan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Bong-Soo Cha
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
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Wang X, Wei S, Wei Y, Wang X, Xiao F, Feng Y, Zhu Q. The impact of concomitant metabolic dysfunction-associated fatty liver disease on adverse outcomes in patients with hepatitis B cirrhosis: a propensity score matching study. Eur J Gastroenterol Hepatol 2023; 35:889-898. [PMID: 37395242 DOI: 10.1097/meg.0000000000002583] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
BACKGROUND AND AIMS In cirrhotic patients, the clinical relevance of metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. We aimed to research the relationship between MAFLD and adverse clinical outcomes in patients with hepatitis B cirrhosis. METHODS A total of 439 patients with hepatitis B cirrhosis were enrolled. Abdominal MRI and computed tomography were used to calculate liver fat content in order to evaluate steatosis. The Kaplan-Meier method was implemented to generate survival curves. The independent risk factors for prognosis were identified by multiple Cox regression. Propensity score matching (PSM) was used to reduce the influence of confounding factors. This study explored the relevance between MAFLD and mortality, first decompensation and further decompensation. RESULTS In our study, most patients were decompensated cirrhosis (n = 332, 75.6%) and the ratio of decompensated cirrhosis patients in non-MAFLD to MAFLD group was 199 : 133. Compared to the non-MAFLD group, patients with MAFLD had worse liver function which mainly reflected that there were more Child-Pugh C patients and higher model for end-stage liver disease score in the MAFLD group. A total of 207 adverse clinical events occurred in the total cohort during a median follow-up of 47 months, including 45 deaths, 28 hepatocellular carcinoma, 23 first decompensation and 111 further decompensation. Cox multivariate analysis showed that MAFLD was an independent risk factor for death [hazard ratio (HR) 1.931; 95% confidence interval (CI) 1.019-3.660; P = 0.044 HR 2.645; 95% CI, 1.145-6.115; P = 0.023] and further decompensation (HR 1.859; 95% CI, 1.261-2.741; P = 0.002 HR 1.953; 95% CI, 1.195-3.192; P = 0.008) before and after PSM. In decompensated group with MAFLD, diabetes had a more significant effect on adverse prognosis than overweight or obesity and other metabolic risk factors. CONCLUSION In patients with hepatitis B cirrhosis, concomitant MAFLD can predict a higher risk of further decompensation and death among decompensated individuals. According to patients among MAFLD, diabetes may be a major factor in the occurrence of adverse clinical events.
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Affiliation(s)
- Xinyu Wang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
| | - Shuhang Wei
- Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan
| | - Yingnan Wei
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
| | - Xueqi Wang
- Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan
| | - Feng Xiao
- Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Taian
| | - Yuemin Feng
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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Chung GE, Yu SJ, Yoo J, Cho Y, Lee K, Shin DW, Kim YJ, Yoon J, Han K, Cho EJ. Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients with metabolic dysfunction-associated fatty liver disease: a population-based cohort study with 9.7 million Korean subjects. Cancer Commun (Lond) 2023; 43:863-876. [PMID: 37337385 PMCID: PMC10397567 DOI: 10.1002/cac2.12454] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 04/30/2023] [Accepted: 06/05/2023] [Indexed: 06/21/2023] Open
Abstract
INTRODUCTION Although an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all- and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease. METHODS Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single-etiology MAFLD (S-MAFLD) or MAFLD of pure metabolic origin; (2) mixed-etiology MAFLD (M-MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non-MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events. RESULTS Among the 9,718,182 participants, the prevalence of S-MAFLD and M-MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow-up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer-related deaths occurred among the entire cohort. Compared with the non-MAFLD group, the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02-1.04; mortality, aHR = 1.06; 95% CI: 1.04-1.08) and highest among patients with M-MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29-1.32; mortality, aHR = 1.45; 95% CI: 1.42-1.48, respectively). The M-MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all-cancer incidence (aHR = 1.38, 95% CI = 1.36-1.39), followed by the M-MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06-1.11). Similar trends were observed for cancer-related mortality. CONCLUSIONS MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer-related outcomes.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine and Healthcare Research InstituteSeoul National University Hospital Healthcare System Gangnam CenterSeoulRepublic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Jeong‐Ju Yoo
- Department of Gastroenterology and HepatologySoonchunhyang University Bucheon HospitalBucheonGyeonggi‐doRepublic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary CancerNational Cancer CenterGoyangGyeonggi‐doRepublic of Korea
| | - Kyu‐na Lee
- Department of Biomedicine & Health ScienceCatholic University of KoreaSeoulRepublic of Korea
| | - Dong Wook Shin
- Department of Family Medicine/ Supportive care centerSamsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
- Department of Clinical Research Design and Evaluation/Department of Digital HealthSamsung Advanced Institute for Health ScienceSeoulRepublic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Jung‐Hwan Yoon
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial ScienceSoongsil UniversitySeoulRepublic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea
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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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Kim BK, Bernstein N, Huang DQ, Tamaki N, Imajo K, Yoneda M, Sutter N, Jung J, Nguyen K, Nguyen L, Le T, Madamba E, Richards L, Valasek MA, Behling C, Sirlin CB, Nakajima A, Loomba R. Clinical and histologic factors associated with discordance between steatosis grade derived from histology vs. MRI-PDFF in NAFLD. Aliment Pharmacol Ther 2023; 58:229-237. [PMID: 37269117 PMCID: PMC10330628 DOI: 10.1111/apt.17564] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 03/29/2023] [Accepted: 05/09/2023] [Indexed: 06/04/2023]
Abstract
BACKGROUND Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an excellent biomarker for the non-invasive quantification of hepatic steatosis. AIM To examine clinical and histologic factors associated with discordance between steatosis grade determined by histology and MRI-PDFF in patients with non-alcoholic fatty liver disease (NAFLD) METHODS: We included 728 patients with biopsy-proven NAFLD from UC San Diego (n = 414) and Yokohama City University (n = 314) who underwent MRI-PDFF and liver biopsy. Patients were stratified by steatosis, and matched with MRI-PDFF cut-points for each steatosis grade: 0 (MRI-PDFF < 6.4%), 1 (MRI-PDFF: 6.4%-17.4%), 2 (MRI-PDFF: 17.4%-22.1%), 3 (MRI-PDFF ≥ 22.1%). Primary outcome was major discordance defined as ≥2 steatosis grade difference determined by histology and MRI-PDFF. RESULTS Mean (±SD) age and BMI were 55.3 (±13.8) years and 29.9 (±4.9) kg/m2 , respectively. The distributions of histology and MRI-PDFF-determined steatosis were 5.5% grade 0 (n = 40), 44.8% 1 (n = 326, 44.8%), 33.9% 2 (n = 247), and 15.8% 3 (n = 115) vs. 23.5% grade 0 (n = 171), 49.7% 1 (n = 362), 12.9% 2 (n = 94), and 13.9% 3 (n = 101). Major discordance rate was 6.6% (n = 48). Most cases with major discordance had greater histology-determined steatosis grade (n = 40, 88.3%), higher serum AST and liver stiffness, and greater likelihood of fibrosis ≥2, ballooning ≥1 and lobular inflammation ≥2 (all p < 0.05). CONCLUSION Histology overestimates steatosis grade compared to MRI-PDFF. Patients with advanced NASH are likely to be upgraded on steatosis grade by histology. These data have important implications for steatosis estimation and reporting on histology in clinical practice and trials, especially in patients with stage 2 fibrosis.
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Affiliation(s)
- Beom Kyung Kim
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Nicole Bernstein
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Daniel Q. Huang
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Nobuharu Tamaki
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
- Department of Gastroenterology, Shin-yurigaoka General Hospital, Kanagawa, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
| | - Nancy Sutter
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Jinho Jung
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Khang Nguyen
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Leyna Nguyen
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Tracy Le
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Egbert Madamba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Lisa Richards
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
| | - Mark A. Valasek
- Department of Pathology, University of California San Diego, La Jolla, CA, United States
| | - Cynthia Behling
- Sharp Medical Group, Department of Pathology, University of California San Diego, La Jolla, CA, United States
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego, La Jolla, CA, United States
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, United States
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States
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Lim Y, Jeong S, Hong M, Han HW. Non-Alcoholic Fatty Liver Disease, Atherosclerosis, and Cardiovascular Disease in Asia. Rev Cardiovasc Med 2023; 24:173. [PMID: 39077515 PMCID: PMC11264113 DOI: 10.31083/j.rcm2406173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/22/2023] [Accepted: 03/02/2023] [Indexed: 07/31/2024] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to increase to over half of the adult population by 2040 globally. Since the final diagnosis of NAFLD is made by a liver biopsy, several non-invasive approaches have been developed and validated to define NAFLD and evaluate NAFLD-associated diseases. Presently, NAFLD has been identified as an important and independent risk factor for developing several extrahepatic diseases, including atherosclerosis, cardiovascular disease (CVD), diabetes, and dementia. This review discusses current findings of up-to-date literature regarding the effects of NAFLD on the risk of atherosclerosis and CVD in Asia along with potential underlying biological mechanisms and therapeutic approaches to lower the NAFLD-related CVD risk. We further focus on the difference between NAFLD and metabolic dysfunction-associated fatty liver disease (MAFLD) on the risk of CVD and its implication by comparing the risk of NAFLD and MAFLD.
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Affiliation(s)
- Yohwan Lim
- Department of Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
- Institute for Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
| | - Seogsong Jeong
- Department of Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
- Institute for Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
| | - Myunghee Hong
- Department of Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
- Institute for Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
| | - Hyun Wook Han
- Department of Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
- Institute for Biomedical Informatics, School of Medicine, CHA University, 13488 Seongnam, Republic of Korea
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30
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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] [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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31
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Tan B, Pan XH, Chew HSJ, Goh RSJ, Lin C, Anand VV, Lee ECZ, Chan KE, Kong G, Ong CEY, Chung HC, Young DY, Chan MY, Khoo CM, Mehta A, Muthiah MD, Noureddin M, Ng CH, Chew NWS, Chin YH. Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Int J Obes (Lond) 2023:10.1038/s41366-023-01321-5. [PMID: 37253796 DOI: 10.1038/s41366-023-01321-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity. METHODS Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively. RESULTS RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide. CONCLUSION Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.
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Affiliation(s)
- Bryan Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Xin-Hui Pan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Han Shi Jocelyn Chew
- Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Rachel Sze Jen Goh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chaoxing Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Vickram Vijay Anand
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Ethan Cheng Zhe Lee
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Gwyneth Kong
- Ministry of Health Holdings, Ministry of Health, Singapore, Singapore
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hui Charlotte Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Dan Yock Young
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Mark Y Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, Singapore, Singapore
| | - Chin Meng Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Endocrinology, National University Hospital, Singapore, Singapore
| | - Anurag Mehta
- VCU Health Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Centre, Cedars-Sinai Medical Centre, Los Angeles, CA, USA
| | - Cheng Han Ng
- Ministry of Health Holdings, Ministry of Health, Singapore, Singapore.
| | - Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Cardiology, National University Heart Centre, Singapore, Singapore
| | - Yip Han Chin
- Ministry of Health Holdings, Ministry of Health, Singapore, Singapore.
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Kang MK, Lee YR, Jang SY, Tak WY, Kweon YO, Song JE, Loomba R, Park SY, Park JG. Impact of metabolic factors on risk of cardiovascular disease in nondiabetic metabolic dysfunction-associated fatty liver disease. Hepatol Int 2023; 17:626-635. [PMID: 37069419 DOI: 10.1007/s12072-023-10517-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 03/07/2023] [Indexed: 04/19/2023]
Abstract
BACKGROUND AND AIM Changing terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) is recently proposed by expert panels based on metabolic dysregulations. However, clinical evidences for the risk of cardiovascular disease (CVD) in MAFLD are limited. The aim of this study is evaluating the association of cardiovascular risk in these two terminology and subgroups of MAFLD. METHODS A total of 2133 individuals who underwent ultrasound and cardiac computed tomography contemporaneously were included at a single medical checkup center. Ultrasound was used to define fatty liver, and coronary artery calcification (CAC) defined a coronary artery calcium score above 0 was used to estimate the cardiovascular risk. RESULTS Overall, 911 participants were diagnosed with fatty liver. In the unadjusted analysis, NAFLD (OR = 1.4, 95% confidence interval [CI] = 1.05-1.85, p = 0.019) and MAFLD (OR = 1.55, 95% CI = 1.29-1.86, p = 0.046) were significantly associated with CAC. However, in sex and age-adjusted analyses, only MAFLD was associated with CAC (adjusted OR [aOR] = 1.38, 95% CI = 1.14-1.69, p = 0.001). Of the three subgroups of MAFLD (diabetic, nondiabetic overweight/obese, and nondiabetic normal weight/lean with at least two metabolic abnormalities), only diabetic MAFLD was associated with CAC (aOR = 2.65, 95% CI = 1.98-3.55, p < 0.001). When the minimal number of metabolic risk abnormalities increased to three, nondiabetic normal-weight/lean MAFLD was associated with CAC (aOR = 1.35, 95% CI = 1.02-1.77, p = 0.034). CONCLUSION Diabetic MAFLD predicted high-risk CVD phenotypes the best. Metabolic risk abnormalities in nondiabetic MAFLD patients were independently associated with the risk of CVD. The proposed diagnostic criteria for nondiabetic MAFLD need further investigation in terms of CVD risk.
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Affiliation(s)
- Min Kyu Kang
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Se Young Jang
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Jeong Eun Song
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Republic of Korea
| | - Rohit Loomba
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, San Diego, CA, USA
- Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, San Diego, CA, USA
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.
| | - Jung Gil Park
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Statin use is associated with better post-operative prognosis among patients with hepatitis B virus-related hepatocellular carcinoma. Eur J Clin Invest 2023; 53:e13936. [PMID: 36504405 DOI: 10.1111/eci.13936] [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: 08/30/2022] [Revised: 12/01/2022] [Accepted: 12/04/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND The high postoperative recurrence rate of hepatocellular carcinoma (HCC) is a significant challenge. Patient metabolic factors are potential disease modifiers and should be examined as risk factors for postoperative prognosis. Here, we assessed the association between long-term statin use and HCC recurrence after surgical resection of hepatitis B virus (HBV)-related HCC. METHODS Patients who initially underwent curative resection for HBV-related HCC between 2005 and 2015 were recruited and followed up until December 2019. Patients were classified into statin user and non-statin user groups based on whether or not they had been prescribed statins for ≥2 years. The primary outcome was HCC recurrence, and the secondary outcome was liver-related mortality. The cumulative incidence by statin use was estimated using the Kaplan-Meier method and compared using the log-rank test. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. RESULTS Among 5653 patients with a median 6.1 years of follow-up, HCC recurrence and liver-related mortality occurred in 1603 and 316 patients, respectively. The 5-year cumulative incidence of HCC recurrence in the statin user group (15.9%) was significantly lower than that in the non-user group (21.3%; p = .019). From multivariable Cox regression analysis, statin use was significantly associated with a reduced risk of HCC recurrence (aHR 0.77, 95% CI: 0.61-0.98; p = .035) and liver-related mortality (aHR 0.48, 95% CI: 0.25-0.90; p = .023). CONCLUSION Long-term statin use was significantly associated with reduced risk of HCC recurrence and liver-related mortality after curative resection of HBV-related HCC.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul, South Korea
| | - Juyeon Oh
- Department of Public Health, Graduate School, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul, South Korea
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Pan J, Ding Y, Sun Y, Li Q, Wei T, Gu Y, Zhou Y, Pang N, Pei L, Ma S, Gao M, Xiao Y, Hu D, Wu F, Yang L. Associations between Adipokines and Metabolic Dysfunction-Associated Fatty Liver Disease Using Three Different Diagnostic Criteria. J Clin Med 2023; 12:jcm12062126. [PMID: 36983127 PMCID: PMC10051925 DOI: 10.3390/jcm12062126] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 02/28/2023] [Accepted: 03/02/2023] [Indexed: 03/11/2023] Open
Abstract
Background: A panel of experts proposed a new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020. To date, the associations between adipokines, such as adiponectin, adipsin, and visfatin and MAFLD remain unclear. Therefore, we aimed to evaluate the associations between each of these three adipokines and MAFLD using different diagnostic criteria. Methods: In total, 221 participants were included in our study based on medical examination. Detailed questionnaire information, physical examination, abdominal ultrasound, and blood-biochemical-test indexes were collected. The levels of adipokines were tested by using an enzyme immunoassay. Logistic regression models were used to assess the associations of the adipokines with MAFLD. Results: In total, 122 of the participants were diagnosed with MAFLD. Higher levels of adipsin and lower levels of adiponectin were found in the MAFLD group than in the non-MAFLD group (all p < 0.05). According to the logistic regression analysis, the ORs were 0.11 (95% CI: 0.05–0.23) for adiponectin, 4.46 (95% CI: 2.19–9.12) for adipsin, and 0.51 (95% CI: 0.27–0.99) for visfatin when comparing the highest tertile with the lowest tertile (all p-trend < 0.05). The inverse association between adiponectin and MAFLD was strongest when T2DM was used as the diagnostic criterion alone, and the positive association between adipsin and MAFLD was strongest when BMI was used as the diagnostic criterion alone. There was no significant association between visfatin and MAFLD, regardless of whether each of BMI, T2DM, or metabolic dysregulation (MD) was used as the diagnostic criterion for MAFLD alone. Conclusion: Adipsin levels were positively associated with MAFLD and adiponectin levels were inversely associated with MAFLD. The strength of these associations varied according to the different diagnostic criteria for MAFLD.
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Affiliation(s)
- Jie Pan
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Yijie Ding
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Yan Sun
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Qiuyan Li
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Tianyi Wei
- Department of Obstetrics, The First Women and Children’s Hospital of Huizhou, Huizhou 516000, China
| | - Yingying Gu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Yujia Zhou
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Nengzhi Pang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Lei Pei
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Sixi Ma
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Mengqi Gao
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Ying Xiao
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - De Hu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Feilong Wu
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
| | - Lili Yang
- Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China
- Correspondence: ; Tel.: +86-20-87330625
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Chun HS, Lee M, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Lee YH, Kim JH, Kim SU. Metabolic dysfunction associated fatty liver disease identifies subjects with cardiovascular risk better than non-alcoholic fatty liver disease. Liver Int 2023; 43:608-625. [PMID: 36585250 DOI: 10.1111/liv.15508] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIMS Cardiovascular disease (CVD) is the main cause of mortality in subjects with non-alcoholic fatty liver disease (NAFLD). We investigated the association between CVD risk and metabolic dysfunction-associated fatty liver disease (MAFLD) or NAFLD and the influence of significant liver fibrosis on the CVD risk. METHODS Subjects who underwent a comprehensive medical check-up were recruited (2014-2019). Significant liver fibrosis was defined using NAFLD fibrosis score, fibrosis-4 index, aspartate aminotransferase to platelet ratio index, or FibroScan-aspartate aminotransferase score. High probability of atherosclerotic CVD (ASCVD) was defined as ASCVD risk score > 10%. RESULTS Of the study population (n = 78 762), 27 047 (34.3%) and 24 036 (30.5%) subjects had MAFLD and NAFLD respectively. A total of 1084 (4.0%) or 921 (3.8%) subjects had previous CVD history in MAFLD or NAFLD subgroup respectively. The previous CVD history and high probability of ASCVD were significantly higher in MAFLD or NAFLD subgroup with significant liver fibrosis than in the other groups (all p < .001). In multivariable analysis, MAFLD was independently associated with previous CVD history after adjusting for confounders (adjusted odds ratio [aOR] = 1.10, p = .038), whereas NAFLD was not (all p > .05). MAFLD (aOR = 1.40) or NAFLD (aOR = 1.22) was independently associated with high probability of ASCVD after full adjustment respectively (all p < .001). Significant liver fibrosis was independently associated with previous CVD history and high probability of ASCVD after adjustment in MAFLD or NAFLD subgroup respectively (all p < .05). CONCLUSION MAFLD might better identify subjects with CVD risk than NAFLD. Fibrosis assessment might be helpful for detailed prognostication in subjects with MAFLD.
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Affiliation(s)
- Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, South Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, South Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Yong-Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji-Hye Kim
- Department of Health Promotion, Yonsei University Health System, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
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Cho Y, Kim BH, Park JW. Preventive strategy for nonalcoholic fatty liver disease-related hepatocellular carcinoma. Clin Mol Hepatol 2023; 29:S220-S227. [PMID: 36353768 PMCID: PMC10029950 DOI: 10.3350/cmh.2022.0360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 09/05/2022] [Indexed: 11/12/2022] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.
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Affiliation(s)
- Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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Nogami A, Yoneda M, Iwaki M, Kobayashi T, Honda Y, Ogawa Y, Imajo K, Saito S, Nakajima A. Non-invasive imaging biomarkers for liver steatosis in non-alcoholic fatty liver disease: present and future. Clin Mol Hepatol 2023; 29:S123-S135. [PMID: 36503207 PMCID: PMC10029939 DOI: 10.3350/cmh.2022.0357] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the global population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination; however, technological innovations have made it possible to evaluate fatty liver by non-invasive imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize the currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.
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Affiliation(s)
- Asako Nogami
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
| | - Masato Yoneda
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
| | - Michihiro Iwaki
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
| | - Takashi Kobayashi
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
| | - Yasushi Honda
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
| | - Yuji Ogawa
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
- Department of Gastroenterology, National Hospital Organization Yokohama Medical Center, Yokohama, Japan
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
- Department of Gastroenterology and Endoscopy, Shinyurigaoka General Hospital, Kawasaki, Japan
| | - Satoru Saito
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate school of Medicine, Yokohama, Japan
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Chen G, Banini B, Do A, Lim JK. The independent effect of exercise on biopsy-proven non-alcoholic fatty liver disease: A systematic review. Clin Mol Hepatol 2023; 29:S319-S332. [PMID: 36517000 PMCID: PMC10029942 DOI: 10.3350/cmh.2022.0366] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 12/09/2022] [Accepted: 12/12/2022] [Indexed: 03/15/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although previous studies have demonstrated that exercise independently reduces hepatic steatosis measured by imaging modalities in NAFLD, the effect of exercise on histological endpoints remains unclear. We aimed to conduct a systematic review of the independent effect of exercise on hepatic steatosis, steatohepatitis, and liver fibrosis as measured by histological assessment or non-invasive tests (NITs) in biopsy-proven NAFLD. A systematic literature search of PubMed, Embase, and Web of Science databases was performed using keywords related to exercise, NAFLD, and biopsy. Articles were selected based on the following inclusion criteria: (1) involved human subjects with biopsy-proven NAFLD, (2) analyzed the independent effect of exercise, (3) assessed changes in hepatic steatosis, steatohepatitis, or liver fibrosis via either histological evaluation or NITs, and (4) were original research studies. We identified a total of six studies that analyzed the independent effect of exercise on histological endpoints in biopsy-proven NAFLD. Two randomized controlled trials (RCTs) did not detect significant histological improvement following exercise interventions, while other non-randomized interventional studies showed that exercise reduces hepatocyte ballooning and liver fibrosis. In addition, five studies assessed NIT outcomes, collectively demonstrating that exercise improves hepatic steatosis measured by magnetic resonance imaging-based techniques but not serum biomarkers for steatohepatitis and liver fibrosis. Additional large RCTs and meta-analyses are warranted to investigate the independent effect of exercise on histological and clinical outcome endpoints in NAFLD.
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Affiliation(s)
- George Chen
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Bubu Banini
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Albert Do
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Joseph K. Lim
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
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Gofton C, Upendran Y, Zheng MH, George J. MAFLD: How is it different from NAFLD? Clin Mol Hepatol 2023; 29:S17-S31. [PMID: 36443926 PMCID: PMC10029949 DOI: 10.3350/cmh.2022.0367] [Citation(s) in RCA: 193] [Impact Index Per Article: 96.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 12/02/2022] Open
Abstract
"Metabolic dysfunction-associated fatty liver disease (MAFLD)" is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.
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Affiliation(s)
- Cameron Gofton
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
- Department of Gastroenterology and Hepatology, Royal North Shore Hospital, St Leonards, NSW, Australia
- Department of Gastroenterology and Hepatology, Bankstown-Lidcombe Hospital, Bankstown, NSW, Australia
- Department of Gastroenterology and Hepatology, University of New South Wales, Sydney, NSW, Australia
| | - Yadhavan Upendran
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Wenzhou Key Laboratory of Hepatology, 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
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia
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Han SK, Baik SK, Kim MY. Non-alcoholic fatty liver disease: Definition and subtypes. Clin Mol Hepatol 2023; 29:S5-S16. [PMID: 36577427 PMCID: PMC10029964 DOI: 10.3350/cmh.2022.0424] [Citation(s) in RCA: 100] [Impact Index Per Article: 50.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/21/2022] [Accepted: 12/24/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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Chung GE, Yu SJ, Yoo JJ, Cho Y, Lee KN, Shin DW, Kim D, Kim YJ, Yoon JH, Han K, Cho EJ. Lean or diabetic subtypes predict increased all-cause and disease-specific mortality in metabolic-associated fatty liver disease. BMC Med 2023; 21:4. [PMID: 36600263 PMCID: PMC9814304 DOI: 10.1186/s12916-022-02716-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/16/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups. METHODS Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models. RESULTS Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59-1.63), 1.36 (1.34-1.38), and 1.19 (1.18-1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72-2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75-2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23-5.97). CONCLUSIONS The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD.
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Affiliation(s)
- Goh Eun Chung
- Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-No, Jongno-Gu, Seoul, 03080, Republic of Korea
| | - Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Kyu-Na Lee
- Department of Biomedicine and Health Science, Catholic University, Seoul, Republic of Korea
| | - Dong Wook Shin
- Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation and Department of Digital Health, Samsung Advanced Institute for Health Science, Seoul, Republic of Korea
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-No, Jongno-Gu, Seoul, 03080, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-No, Jongno-Gu, Seoul, 03080, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea.
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-No, Jongno-Gu, Seoul, 03080, Republic of Korea.
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Lu Y, Ge L, Yang H, He Y, Wang Y. Chinese Visceral Adipose Index Shows Superior Diagnostic Performance in Predicting the Risk of Metabolic Dysfunction Associated Fatty Liver Disease in Early Postmenopausal Chinese Women. Diabetes Metab Syndr Obes 2023; 16:607-617. [PMID: 36909348 PMCID: PMC9999715 DOI: 10.2147/dmso.s402814] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 02/24/2023] [Indexed: 03/08/2023] Open
Abstract
BACKGROUND Previous studies have reported the diagnostic values of multiple obesity indicators for predicting the risk of non-alcoholic fatty liver disease. However, the diagnostic values of obesity indicators for predicting the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in early postmenopausal women is still unknown. Therefore, this study investigated the predictive values of common obesity indices for estimating the risk of MAFLD in early postmenopausal Chinese women. METHODS This study enrolled 2514 early postmenopausal women, aged between 45 and 55 years, who underwent abdominal ultrasonography examination at the Health examination center of the Huadong Sanatorium between June 2021 and December 2021. The values for six obesity indices, namely, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI), and Chinese visceral adiposity index (CVAI) were extracted from the medical records. RESULTS Our data showed that all the six obesity indices were significantly associated with the risk of MAFLD (P < 0.05) in the obese subjects and five obesity indices except for BAI were significantly associated with the risk of MAFLD (P < 0.05) in the lean subjects. The six obesity indices showed a linear relationship with the risk of MAFLD (all P-values > 0.05). The ORs for the obesity indices with the exception of BAI showed proportional increase with the risk of MAFLD in the lean subjects. CVAI was the strongest predictor of the risk of MAFLD in both lean (AUC=0.868) and overweight/obese subjects (AUC=0.704) among the early postmenopausal women. CONCLUSION This study demonstrated that all the obesity indices were associated with an increased risk of MAFLD in the obese subjects and five obesity indices except for BAI were associated with an increased risk of MAFLD in the lean subjects among the early postmenopausal women. CVAI showed the strongest predictive performance in estimating the risk of MAFLD among early menopausal women.
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Affiliation(s)
- Yayun Lu
- Health Examination Center, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Lingxia Ge
- Health Examination Center, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Hao Yang
- Department of Stomatology, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Yufeng He
- Department of Stomatology, Huadong Sanatorium, Wuxi, People’s Republic of China
| | - Yujun Wang
- Department of health Nursing, Huadong Sanatorium, Wuxi, People’s Republic of China
- Correspondence: Yujun Wang, Department of health nursing, Huadong Sanatorium, Wuxi, No. 67 Jinyuan Road, People’s Republic of China, Tel +86 13912359439, Email
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Liu L, Geng Y, Xiong C. Impact of Porphyromonas gingivalis-odontogenic infection on the pathogenesis of non-alcoholic fatty liver disease. Ann Med 2023; 55:2255825. [PMID: 37708866 PMCID: PMC10503456 DOI: 10.1080/07853890.2023.2255825] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 06/15/2023] [Accepted: 09/01/2023] [Indexed: 09/16/2023] Open
Abstract
Aim: Non-alcoholic fatty liver disease is characterized by diffuse hepatic steatosis and has quickly risen to become the most prevalent chronic liver disease. Its incidence is increasing yearly, but the pathogenesis is still not fully understood. Porphyromonas gingivalis (P. gingivalis) is a major pathogen widely prevalent in periodontitis patients. Its infection has been reported to be a risk factor for developing insulin resistance, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and metabolic syndrome. The aim of this review is to evaluate the association between P. gingivalis infection and NAFLD, identify the possible etiopathogenetic mechanisms, and raise public awareness of oral health to prevent and improve NAFLD.Methods: After searching in PubMed and Web of Science databases using 'Porphyromonas gingivalis', 'non-alcoholic fatty liver disease', and 'hepatic steatosis' as keywords, studies related were compiled and examined.Results: P. gingivalis infection is a direct risk factor for NAFLD based on clinical and basic research. Moreover, it induces systematic changes and systemic abnormalities by disrupting metabolic, inflammatory, and immunologic homeostasis.Conclusion: P. gingivalis-odontogenic infection promotes the occurrence and development of NAFLD. Further concerns are needed to emphasize oral health and maintain good oral hygiene for the prevention and treatment of NAFLD.
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Affiliation(s)
- Linbo Liu
- Department of Clinical Laboratory, Yulin No.2 Hospital, Yulin, Shaanxi, China
| | - Yan Geng
- Department of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chaoliang Xiong
- Department of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 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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Comparable Mortality Between Asian Patients with Chronic Hepatitis B Under Long-Term Antiviral Therapy vs Matched Control: A Population-Based Study. Am J Gastroenterol 2022:00000434-990000000-00555. [PMID: 36288330 DOI: 10.14309/ajg.0000000000002074] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 10/06/2022] [Indexed: 12/05/2022]
Abstract
INTRODUCTION Antiviral therapy (AVT) substantially improved the prognosis for patients with chronic hepatitis B (CHB). Head-to-head comparisons of prognosis between treated patients with CHB and the general population are scarce. We directly compared the prognosis between Asian patients with CHB receiving AVT and the general population. METHODS From the South Korean National Health Insurance Service database, patients with CHB receiving AVT ≥3 years, aged 40-64 years, who underwent health examinations between 2011 and 2012 (AVT-CHB group) were recruited. As a control, propensity score-matched general population was chosen among patients without CHB. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular disease (CVD), hepatocellular carcinoma (HCC), and all types of non-HCC malignancies. RESULTS During follow-up (median 7.2 years), 26,467 and 75,469 individuals in the AVT-CHB group and matched general population were analyzed. The 5- and 7-year cumulative all-cause mortality rates were 0.40% and 1.0% for the AVT-CHB group vs 0.50% and 1.0% for the matched general population (adjusted hazard ratio [aHR] 0.96, 95% confidence interval [CI] 0.83-1.10; P = 0.51). The AVT-CHB group had a lower risk of CVD than the matched general population (aHR 0.70, 95% CI: 0.62-0.79; P < 0.001). Although the AVT-CHB group was more likely to develop HCC than the matched general population (aHR 13.16, 95% CI: 10.90-15.89; P < 0.001), the non-HCC malignancy risks in the AVT-CHB group were comparable to the matched general population (aHR 1.05, 95% CI 0.98-1.13; P = 0.137). DISCUSSION The AVT-CHB group had a similar risk of all-cause mortality and non-HCC malignancies and a lower risk of CVD than the matched general population.
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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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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Effect of metabolic dysfunction-associated fatty liver disease on liver cancer risk in a population with chronic hepatitis B virus infection: A nationwide study. Hepatol Res 2022; 52:975-984. [PMID: 35976670 DOI: 10.1111/hepr.13830] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/28/2022] [Accepted: 08/16/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The association between metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatocellular carcinoma (HCC) lacks clinical validation in at-risk populations. We assessed this relationship among chronic hepatitis B (CHB) patients. METHODS Data was collected from the National Health Insurance System database in South Korea. Chronic hepatitis B patients aged over 40 years receiving health examinations between 2011 and 2012 were recruited. The primary outcome was HCC. Metabolic dysfunction-associated fatty liver disease was defined as hepatic steatosis in combination with at least one of the following: (i) overweight, (ii) diabetes, or (iii) lean/normal weight with two or more metabolic components. Multivariable Cox regression analysis was used to estimate adjusted hazard ratios (aHRs). RESULTS Of 197 346 participants, 66 149 had MAFLD; 19 149, 44 475, and 2525 fulfilled diabetes (regardless of overweight), overweight alone, and lean/normal weight with two or more metabolic components, respectively. During follow-up (median 7 years), 13 771 developed HCC. Metabolic dysfunction-associated fatty liver disease was independently associated with increased risk of HCC, with aHR of 1.36 (p < 0.001). Propensity score matching confirmed the same phenomena, with aHR of 1.37 (p < 0.001). Furthermore, when stratified by liver cirrhosis and/or antiviral therapy, independent significances of MAFLD for HCC risk were maintained (all p < 0.001). Compared with the persistent non-MAFLD subgroup during the entire follow-up, diagnosis of MAFLD from at least one health examination significantly increased HCC risk with aHRs of 1.41, 1.37, and 1.14 among subgroups with persistent MAFLD, MAFLD to non-MAFLD, and non-MAFLD to MAFLD, respectively (all p < 0.05). CONCLUSIONS Metabolic dysfunction-associated fatty liver disease consistently increases HCC risk among CHB patients. Further studies are needed to develop an effective preventive strategy through control of metabolic health.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Juyeon Oh
- Department of Public Health, Graduate School, Yonsei University, Seoul, Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.,Department of Occupational Health, Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.,Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.,Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
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Attia D, Abdel Alem S, El-Akel W, Abdel-Razek W, Eslam M, Fouad Y, Waked I. Prevalence and clinical characteristics of patients with metabolic dysfunction-associated fatty liver disease with hepatitis C virus infection-a population-based study. Aliment Pharmacol Ther 2022; 56:1581-1590. [PMID: 36168675 DOI: 10.1111/apt.17233] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/05/2022] [Accepted: 09/11/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to identify fatty liver disease associated with metabolic risks. Metabolic abnormalities with hepatitis C virus (HCV) and MAFLD frequently co-exist. However, data on the co-existence are still lacking. AIM To explore the prevalence and characteristics of metabolic profiles among a large cohort of patients with HCV infection between 2007 and 2020 based on new diagnostic criteria METHODS: We recruited 288,222 patients with chronic HCV infection with demographic data, laboratory parameters, and ultrasound from a web-based registry of the National Committee for Control of Viral Hepatitis in Egypt from 2007 to 2020. RESULTS Among the participants, 41.9% (95% CI: 41.69-42.05) met diagnostic criteria for MAFLD, with a significant increase in the period 2014-2020 compared to 2007-2013 (43.3% vs. 19%, respectively). Participants with MAFLD had a high prevalence of obesity, diabetes mellitus and hypertension. The prevalences increased significantly over time (obesity: 66.7% vs. 76.9%, p < 0.01; diabetes mellitus: 14.6% vs. 31.5%, p < 0.01; hypertension: 0.9% vs. 7.6%, p < 0.01; prediabetes: 28.8% vs. 25.9%, p < 0.01) for the periods 2007-2013 and 2014-2020, respectively. The percentage of advanced fibrosis by fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) was significantly higher in participants with MAFLD during 2014-2020 than during 2007-2013 (FIB-4; 18.4% vs. 8% and NFS; 17.1% vs. 7%). CONCLUSION MAFLD is highly prevalent in patients with HCV infection and has risen over time. This rising prevalence parallels the alarming rise in obesity, diabetes mellitus and hypertension. Early detection of metabolic dysfunction in patients with HCV infection is recommended to prevent MAFLD progression.
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Affiliation(s)
- Dina Attia
- Beni-Suef University, Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni Suef, Egypt
| | - Shereen Abdel Alem
- Cairo University, Department of Endemic Medicine, Faculty of Medicine, Cairo, Egypt
| | - Wafaa El-Akel
- Cairo University, Department of Endemic Medicine, Faculty of Medicine, Cairo, Egypt
| | - Wael Abdel-Razek
- Ain Shams University (MOH), Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Cairo, Egypt
| | - Mohamed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Westmead, New South Wales, Australia
- University of Sydney, Sydney, New South Wales, Australia
| | - Yasser Fouad
- Minia University, Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia, Egypt
| | - Imam Waked
- National Liver Institute, Department of Hepatology, Shebeen el Kom, Egypt
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Pansa CC, Molica LR, Moraes KCM. Non-alcoholic fatty liver disease establishment and progression: genetics and epigenetics as relevant modulators of the pathology. Scand J Gastroenterol 2022; 58:521-533. [PMID: 36426638 DOI: 10.1080/00365521.2022.2148835] [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] [Indexed: 11/26/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) results from metabolic dysfunctions that affect more than one-third of the world population. Over the last decades, scientific investigations have clarified many details on the pathology establishment and development; however, effective therapeutics approaches are still evasive. In addition, studies demonstrated that NAFLD establishment and progression are related to several etiologies. Recently, genetics and epigenetics backgrounds have emerged as relevant elements to the pathology onset, and, hence, deserve deep investigation to clarify molecular details on NAFLD signaling, which may be correlated with population behavior. Thus, to minimize the global problem, public health and public policies should take advantage of studies on NAFLD over the next following decades. METHODS In this context, we have performed a selective literature review focusing on biochemistry of lipid metabolism, genetics, epigenetics, and the ethnicity as strong elements that drive NAFLD establishment. RESULTS Considering the etiological agents that acts on NAFLD development and progression, the genetics and the epigenetics emerged as relevant factors. Genetics acts as a powerful element in the establishment and progression of the NAFLD. Over the last decades, details concerning genes and their polymorphisms, as well as epigenetics, have been considered relevant elements in the systems biology of diseases, and their effects on NAFLD should be considered in-depth, as well as the ethnicity, clarifying whether people are susceptible to liver diseases. Moreover, the endemicity and social problems of hepatic disfunction are far to be solved, which require a combined effort of various sectors of society. CONCLUSION Hence, the elements presented and discussed in this short review demonstrated their relevance to the physiological control of NAFLD, opening perspectives for research to develop new strategy to treat fatty liver diseases.
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Affiliation(s)
- Camila Cristiane Pansa
- Departamento de Biologia Geral e Aplicada, Cellular Signalling and Gene Expression Laboratory, Universidade Estadual Paulista "Júlio de Mesquita Filho", Instituto de Biociências, Rio Claro, Brazil
| | - Letícia Ramos Molica
- Departamento de Biologia Geral e Aplicada, Cellular Signalling and Gene Expression Laboratory, Universidade Estadual Paulista "Júlio de Mesquita Filho", Instituto de Biociências, Rio Claro, Brazil
| | - Karen C M Moraes
- Departamento de Biologia Geral e Aplicada, Cellular Signalling and Gene Expression Laboratory, Universidade Estadual Paulista "Júlio de Mesquita Filho", Instituto de Biociências, Rio Claro, Brazil
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Yun B, Ahn SH, Oh J, Yoon JH, Kim BK. Prognostic Impact of MAFLD Following Surgical Resection of Hepatitis B Virus-Related Hepatocellular Carcinoma: A Nationwide Cohort Study. Cancers (Basel) 2022; 14:5002. [PMID: 36291786 PMCID: PMC9599346 DOI: 10.3390/cancers14205002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/12/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
The association between the metabolic effects of hepatic steatosis as a part of postoperative outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has rarely been studied. This study aimed to assess the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and patients’ prognoses following curative resection of HBV-related HCC. Patients who underwent surgical resection for HBV-related HCC between 2009 and 2015 were recruited. The study endpoints were postoperative hepatocellular carcinoma (HCC) recurrence and all-cause mortality. Adjusted hazard ratios (aHRs) for the outcomes were estimated using multivariate Cox regression models. The mean age of the 2032 enrolled patients was 55.0 years, and 77.9% were men. During follow-up (median 5.3 years), HCC recurrence and all-cause mortality occurred in 954 (47.0%) and 422 (20.8%) patients, respectively. HCC recurrence and all-cause mortality were significantly associated with MAFLD, with aHRs of 1.22 (p = 0.003) and 1.44 (p < 0.001), respectively. Propensity score matching and inverse probability treatment weighting analyses confirmed similar results (p < 0.05). MAFLD was associated with significantly poor prognoses in terms of HCC recurrence and all-cause mortality following surgical resection of HBV-related HCC. Further studies are needed to develop an effective preventive strategy through the management of metabolic health.
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Affiliation(s)
- Byungyoon Yun
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
| | - Juyeon Oh
- Department of Public Health, Yonsei University Graduate School, Seoul 03722, Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- The Institute for Occupational Health, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, Korea
- Yonsei Liver Centre, Severance Hospital, Yonsei University Health System, Seoul 03722, Korea
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