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Lin L, Lai J, Luo L, Ye J, Zhong B. Ethnic differences in metabolic and histologic features among White, Hispanic, Black and Asian patients with metabolic-associated Steatotic liver disease: A network meta-analysis. Ann Hepatol 2025; 30:101780. [PMID: 39952324 DOI: 10.1016/j.aohep.2025.101780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/18/2024] [Accepted: 12/26/2024] [Indexed: 02/17/2025]
Abstract
INTRODUCTION AND OBJECTIVES Current evidence on the impact of ethnic disparities on metabolic-associated steatotic liver disease (MASLD) is limited to individual studies with small sample sizes from specific regions. This network meta-analysis aimed to assess variations in metabolism and histological characteristics of MASLD among four ethnicities. MATERIALS AND METHODS Observational studies on MASLD involving at least two ethnic groups (White, Black, Asian, and Hispanic) were identified from PubMed, Embase, and Web of Science databases up to May 7th, 2024, for inclusion in this study. The results were reported as unstandardized mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS A total of twenty-seven articles involving 14,440 non-Hispanic Whites, 4,927 non-Hispanic Blacks, 5,254 Asians, and 8,344 Hispanic MASLD patients were included in this study. The prevalence of type 2 diabetes mellitus of all ethnic groups combined was 33%, without significant difference among the four ethnicities. Asians showed higher levels of total cholesterol compared to the other groups, while Blacks had the lowest levels of alanine aminotransferase. Among biopsy-proven MASLD patients, Blacks individuals had a lower risk of significant fibrosis compared to Whites (OR=0.63, 95% CI: 0.45 to 0.87), as well as lower risks of liver inflammation (OR=0.53, 95% CI: 0.29 to 0.95) and nonalcoholic steatohepatitis (NASH) (OR=0.53, 95% CI: 0.29 to 0.95) compared to Hispanics. CONCLUSIONS Asians MASLD patients had higher risk of suffering from abnormal lipid metabolism while Black MASLD patients presented milder liver histologic features than both Whites and Hispanics individuals.
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Affiliation(s)
- Limin Lin
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China
| | - Jiaming Lai
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China
| | - Ling Luo
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China
| | - Junzhao Ye
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China.
| | - Bihui Zhong
- Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China.
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Besser LM, Forrester SN, Arabadjian M, Bancks MP, Culkin M, Hayden KM, Le ET, Pierre-Louis I, Hirsch JA. Structural and social determinants of health: The multi-ethnic study of atherosclerosis. PLoS One 2024; 19:e0313625. [PMID: 39556532 PMCID: PMC11573213 DOI: 10.1371/journal.pone.0313625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 10/28/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND Researchers have increasingly recognized the importance of structural and social determinants of health (SSDOH) as key drivers of a multitude of diseases and health outcomes. The Multi-Ethnic Study of Atherosclerosis (MESA) is an ongoing, longitudinal cohort study of subclinical cardiovascular disease (CVD) that has followed geographically and racially/ethnically diverse participants starting in 2000. Since its inception, MESA has incorporated numerous SSDOH assessments and instruments to study in relation to CVD and aging outcomes. In this paper, we describe the SSDOH data available in MESA, systematically review published papers using MESA that were focused on SSDOH and provide a roadmap for future SSDOH-related studies. METHODS AND FINDINGS The study team reviewed all published papers using MESA data (n = 2,125) through January 23, 2023. Two individuals systematically reviewed titles, abstracts, and full text to determine the final number of papers (n = 431) that focused on at least one SSDOH variable as an exposure, outcome, or stratifying/effect modifier variable of main interest (discrepancies resolved by a third individual). Fifty-seven percent of the papers focused on racialized/ethnic groups or other macrosocial/structural factors (e.g., segregation), 16% focused on individual-level inequalities (e.g. income), 14% focused on the built environment (e.g., walking destinations), 10% focused on social context (e.g., neighborhood socioeconomic status), 34% focused on stressors (e.g., discrimination, air pollution), and 4% focused on social support/integration (e.g., social participation). Forty-seven (11%) of the papers combined MESA with other cohorts for cross-cohort comparisons and replication/validation (e.g., validating algorithms). CONCLUSIONS Overall, MESA has made significant contributions to the field and the published literature, with 20% of its published papers focused on SSDOH. Future SSDOH studies using MESA would benefit by using recently added instruments/data (e.g., early life educational quality), linking SSDOH to biomarkers to determine underlying causal mechanisms linking SSDOH to CVD and aging outcomes, and by focusing on intersectionality, understudied SSDOH (i.e., social support, social context), and understudied outcomes in relation to SSDOH (i.e., sleep, respiratory health, cognition/dementia).
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Affiliation(s)
- Lilah M. Besser
- Department of Neurology, Comprehensive Center for Brain Health, University of Miami, Boca Raton, Florida, United States of America
| | - Sarah N. Forrester
- Division of Epidemiology, Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America
| | - Milla Arabadjian
- Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, United States of America
| | - Michael P. Bancks
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
| | - Margaret Culkin
- Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
| | - Kathleen M. Hayden
- Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
| | - Elaine T. Le
- Department of Neurology, Comprehensive Center for Brain Health, University of Miami, Boca Raton, Florida, United States of America
| | - Isabelle Pierre-Louis
- Division of Epidemiology, Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America
| | - Jana A. Hirsch
- Urban Health Collaborative and Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania, United States of America
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Pan Z, Khatry MA, Yu ML, Choudhury A, Sebastiani G, Alqahtani SA, Eslam M. MAFLD: an ideal framework for understanding disease phenotype in individuals of normal weight. Ther Adv Endocrinol Metab 2024; 15:20420188241252543. [PMID: 38808010 PMCID: PMC11131400 DOI: 10.1177/20420188241252543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/10/2024] [Indexed: 05/30/2024] Open
Abstract
The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.
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Affiliation(s)
- Ziyan Pan
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Maryam Al Khatry
- Department of Gastroenterology, Obaidullah Hospital, Emirates Health Services, Ministry of Health, Ras Al Khaimah, United Arab Emirates
| | - Ming-Lung Yu
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Giada Sebastiani
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Saleh A. Alqahtani
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, 176 Hawkesbury Road, Westmead 2145, NSW, Australia
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Ito Y, Yoshioka K, Hayashi K, Shimizu Y, Fujimoto R, Yamane R, Yoshizaki M, Kajikawa G, Mizutani T, Goto H. Prevalence of Non-alcoholic Fatty Liver Disease Detected by Computed Tomography in the General Population Compared with Ultrasonography. Intern Med 2024; 63:159-167. [PMID: 37225482 PMCID: PMC10864065 DOI: 10.2169/internalmedicine.1861-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 04/09/2023] [Indexed: 05/26/2023] Open
Abstract
Objective To assess the prevalence and clinical correlates of non-alcoholic fatty liver disease (NAFLD) identified by computed tomography (CT) in the general population compared with ultrasonography (US). Methods Four hundred and fifty-eight subjects who received health checkups at Meijo Hospital in 2021 and underwent CT within a year of US in the past decade were analyzed. The mean age was 52.3±10.1 years old, and 304 were men. Results NAFLD was diagnosed in 20.3% by CT and in 40.4% by the US. The NAFLD prevalence in men was considerably greater in subjects 40-59 years old than in those ≤39 years old and in those ≥60 years old by both CT and US. The NAFLD prevalence in women was substantially higher in the subjects 50-59 years old than in those ≤49 years old or those ≥60 years old on US, while no significant differences were observed on CT. The abdominal circumference, hemoglobin value, high-density lipoprotein cholesterol level, albumin level, and diabetes mellitus were independent predictors of NAFLD diagnosed by CT. The body mass index, abdominal circumference, and triglyceride level were independent predictors of NAFLD diagnosed by the US. Conclusion NAFLD was found in 20.3% of CT cases and 40.4% of US cases among recipients of health checkups. An "inverted U curve" in which the NAFLD prevalence rose with age and dropped in late adulthood was reported. NAFLD was associated with obesity, the lipid profile, diabetes mellitus, hemoglobin values, and albumin levels. Our research is the first in the world to compare the NAFLD prevalence in the general population simultaneously by CT and US.
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Affiliation(s)
- Yuki Ito
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Kentaro Yoshioka
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Yuko Shimizu
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Ryo Fujimoto
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Ryosuke Yamane
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Michiyo Yoshizaki
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Go Kajikawa
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Taro Mizutani
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Japan
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Mawson AR. Understanding health disparities affecting people of West Central African descent in the United States: An evolutionary perspective. Evol Appl 2023; 16:963-978. [PMID: 37216026 PMCID: PMC10197229 DOI: 10.1111/eva.13549] [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: 01/28/2022] [Revised: 03/19/2023] [Accepted: 04/02/2023] [Indexed: 05/24/2023] Open
Abstract
Human populations adapting to diverse aspects of their environment such as climate and pathogens leave signatures of genetic variation. This principle may apply to people of West Central African descent in the United States, who are at increased risk of certain chronic conditions and diseases compared to their European counterparts. Less well known is that they are also at reduced risk of other diseases. While discriminatory practices in the United States continue to affect access to and the quality of healthcare, the health disparities affecting African Americans may also be due in part to evolutionary adaptations to the original environment of sub-Saharan Africa, which involved continuous exposure to the vectors of potentially lethal endemic tropical diseases. Evidence is presented that these organisms selectively absorb vitamin A from the host, and its use in parasite reproduction contributes to the signs and symptoms of the respective diseases. These evolutionary adaptations included (1) sequestering vitamin A away from the liver to other organs, to reduce accessibility to the invaders; and (2) reducing the metabolism and catabolism of vitamin A (vA), causing it to accumulate to subtoxic concentrations and weaken the organisms, thereby reducing the risk of severe disease. However, in the environment of North America, lacking vA-absorbing parasites and with a mainly dairy-based diet that is high in vA, this combination of factors is hypothesized to lead to the accumulation of vA and to increased sensitivity to vA as a toxin, which contribute to the health disparities affecting African Americans. vA toxicity is linked to numerous acute and chronic conditions via mitochondrial dysfunction and apoptosis. Subject to testing, the hypothesis suggests that the adoption of traditional or modified West Central African-style diets that are low in vA and high in vA-absorbing fiber hold promise for disease prevention and treatment, and as a population-based strategy for health maintenance and longevity.
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Affiliation(s)
- Anthony R. Mawson
- Department of Epidemiology and Biostatistics, School of Public Health, College of Health SciencesJackson State UniversityJacksonMississippiUSA
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Le MH, Yeo YH, Li X, Li J, Zou B, Wu Y, Ye Q, Huang DQ, Zhao C, Zhang J, Liu C, Chang N, Xing F, Yan S, Wan ZH, Tang NSY, Mayumi M, Liu X, Liu C, Rui F, Yang H, Yang Y, Jin R, Le RHX, Xu Y, Le DM, Barnett S, Stave CD, Cheung R, Zhu Q, Nguyen MH. 2019 Global NAFLD Prevalence: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:2809-2817.e28. [PMID: 34890795 DOI: 10.1016/j.cgh.2021.12.002] [Citation(s) in RCA: 367] [Impact Index Per Article: 122.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 11/25/2021] [Accepted: 12/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of nonalcoholic fatty liver disease (NAFLD). We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD. METHODS Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence. RESULTS We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% confidence interval [CI], 28.6%-31.1%); of these, 82.5% of included articles used ultrasound to diagnose NAFLD, with prevalence of 30.6% (95% CI, 29.2%-32.0%). South America (3 studies, 5716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI, 34.0%-37.5%) and 35.3% (95% CI, 25.4%-45.9%), respectively. From 1991 to 2019, trend analysis showed NAFLD increased from 21.9% to 37.3% (yearly increase of 0.7%, P < .0001), with South America showing the most rapid change of 2.7% per year, followed by Europe at 1.1%. CONCLUSIONS Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work toward reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
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Affiliation(s)
- Michael H Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, California
| | - Xiaohe Li
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Infectious Disease, The Third People's Hospital of Shenzhen, Shenzhen, China
| | - Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California
| | - Yuankai Wu
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qing Ye
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; The Third Central Clinical College of Tianjin Medical University, Tianjin; Department of Hepatology of The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Artificial Cells, Tianjin, China
| | - Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine and Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Jie Zhang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Chenxi Liu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Na Chang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Feng Xing
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of T.C.M., Shanghai, China
| | - Shiping Yan
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Zi Hui Wan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Natasha Sook Yee Tang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Maeda Mayumi
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Xinting Liu
- Medical School of Chinese People's Liberation Army, Beijing, and Department of Pediatrics, the First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chuanli Liu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Fajuan Rui
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Hongli Yang
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Yao Yang
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Ruichun Jin
- Jining Medical University, Jining, Shandong, China
| | - Richard H X Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Yayun Xu
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - David M Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Scott Barnett
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | | | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan, Shandong, China
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California.
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Eslam M, El-Serag HB, Francque S, Sarin SK, Wei L, Bugianesi E, George J. Metabolic (dysfunction)-associated fatty liver disease in individuals of normal weight. Nat Rev Gastroenterol Hepatol 2022; 19:638-651. [PMID: 35710982 DOI: 10.1038/s41575-022-00635-5] [Citation(s) in RCA: 132] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/13/2022] [Indexed: 12/12/2022]
Abstract
Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects up to a third of the global population; its burden has grown in parallel with rising rates of type 2 diabetes mellitus and obesity. MAFLD increases the risk of end-stage liver disease, hepatocellular carcinoma, death and liver transplantation and has extrahepatic consequences, including cardiometabolic disease and cancers. Although typically associated with obesity, there is accumulating evidence that not all people with overweight or obesity develop fatty liver disease. On the other hand, a considerable proportion of patients with MAFLD are of normal weight, indicating the importance of metabolic health in the pathogenesis of the disease regardless of body mass index. The clinical profile, natural history and pathophysiology of patients with so-called lean MAFLD are not well characterized. In this Review, we provide epidemiological data on this group of patients and consider overall metabolic health and metabolic adaptation as a framework to best explain the pathogenesis of MAFLD and its heterogeneity in individuals of normal weight and in those who are above normal weight. This framework provides a conceptual schema for interrogating the MAFLD phenotype in individuals of normal weight that can translate to novel approaches for diagnosis and patient care.
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
| | - Hashem B El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology and Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.
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8
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Kubiliun MJ, Cohen JC, Hobbs HH, Kozlitina J. Contribution of a genetic risk score to ethnic differences in fatty liver disease. Liver Int 2022; 42:2227-2236. [PMID: 35620859 PMCID: PMC9427702 DOI: 10.1111/liv.15322] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 05/23/2022] [Accepted: 05/25/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIMS Susceptibility to fatty liver disease (FLD) varies among individuals and between racial/ethnic groups. Several genetic variants influence FLD risk, but whether these variants explain racial/ethnic differences in FLD prevalence is unclear. We examined the contribution of genetic risk factors to racial/ethnic-specific differences in FLD. METHODS A case-control study comparing FLD patients (n = 1194) and population-based controls (n = 3120) was performed. Patient characteristics, FLD risk variants (PNPLA3-rs738409 + rs6006460, TM6SF2-rs58542926, HSD17B13-rs80182459 + rs72613567, MBOAT7/TMC4-rs641738, and GCKR-rs1260326) and a multi-locus genetic risk score (GRS) were examined. The odds of FLD for individuals with different risk factor burdens were determined. RESULTS Hispanics and Whites were over-represented (56% vs. 38% and 36% vs. 29% respectively) and Blacks under-represented (5% vs. 23%) among FLD patients, compared to the population from which controls were selected (p < .001). Among cases and controls, Blacks had a lower and Hispanics a greater, net number of risk alleles than Whites (p < .001). GRS was associated with increased odds of FLD (ORQ5vsQ1 = 8.72 [95% CI = 5.97-13.0], p = 9.8 × 10-28 ), with the association being stronger in Hispanics (ORQ5vsQ1 = 14.8 [8.3-27.1]) than Blacks (ORQ5vsQ1 = 3.7 [1.5-11.5], P-interaction = 0.002). After accounting for GRS, the odds of FLD between Hispanics and Whites did not differ significantly (OR = 1.06 [0.87-1.28], p = .58), whereas Blacks retained much lower odds of FLD (OR = 0.21, [0.15-0.30], p < .001). CONCLUSIONS Blacks had a lower and Hispanics a greater FLD risk allele burden than Whites. These differences contributed to, but did not fully explain, racial/ethnic differences in FLD prevalence. Identification of additional factors protecting Blacks from FLD may provide new targets for prevention and treatment of FLD.
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Affiliation(s)
- Maddie J. Kubiliun
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Jonathan C. Cohen
- The Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas, USA,The Eugene McDermott Center of Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Helen H. Hobbs
- The Eugene McDermott Center of Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Julia Kozlitina
- The Eugene McDermott Center of Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA,Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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9
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Abstract
The association between severe acute malnutrition (SAM) in early childhood and liver fat in adults is unknown. We hypothesized that exposure to SAM, especially severe wasting, is associated with fatty liver later in life. In this observational study, abdominal CT was used to quantify mean liver attenuation (MLA) and liver:spleen attenuation ratio (L/S). Birth weight (BW), serum lipids, insulin resistance (homeostatic model assessment), anthropometry and intrabdominal fat were collected. Mean differences between diagnostic groups were tested and hierarchical regression analysis determined the best predictors of liver fat. We studied 88 adult SAM survivors and 84 community participants (CPs); age 29.0 ± 8.4 years, BMI 23.5 ± 5.0 kg/m2 (mean ± SDs). SAM survivors had less liver fat than CPs (using L/S) (p = 0.025). Severe wasting survivors (SWs) had lower BW (-0.51 kg; p = 0.02), were younger, thinner and had smaller waist circumference than oedematous malnutrition survivors (OMs). In the final regression model adjusting for age, sex, birth weight and SAM phenotype (i.e., oedematous malnutrition or severe wasting), SWs had more liver fat than OMs (using MLA) (B = 2.6 ± 1.3; p = 0.04) but similar liver fat using L/S (p = 0.07) and lower BW infants had less liver fat (MLA) (B = -1.8 ± 0.8; p = 0.03). Greater liver fat in SWs than OMs, despite having less body fat, supports our hypothesis of greater cardiometabolic risk in SWs. Other postnatal factors might influence greater liver fat in survivors of severe wasting, suggesting the need to monitor infants exposed to SAM beyond the acute episode.
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Potential relation between non-alcoholic fatty liver disease and glycemic and metabolic parameters in subjects without diabetes. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00154-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is proved to be related to insulin resistance and type 2 diabetes, and it is also not rare in individuals without diabetes. The present study attempts to identify the metabolic risk factors of NAFLD among those individuals.
Results
ALT and HbA1c levels were independently associated with NAFLD development in individuals without diabetes. Receiver operating characteristic (ROC) analysis identified the optimal cutoff point of ALT (> 19 IU/ml) with AUC = 0.731, 95% CI 0.653–0.809. On the other hand, the optimal cutoff point of HbA1c was identified to be > 5.1% with AUC = 0.665, 95% CI 0.581–0.750.
Conclusions
Early identification of NAFLD among subjects without diabetes is crucial. In this study, ALT and HbA1c cutoff values had been identified, so we suggest that inclusion of both HbA1c and ALT levels may have significant implications for prediction of NAFLD among individuals without diabetes.
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11
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Bonacini M, Kassamali F, Kari S, Lopez Barrera N, Kohla M. Racial differences in prevalence and severity of non-alcoholic fatty liver disease. World J Hepatol 2021; 13:763-773. [PMID: 34367497 PMCID: PMC8326166 DOI: 10.4254/wjh.v13.i7.763] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/08/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
The aim of this review is to assess the evidence regarding racial differences in the prevalence and severity of nonalcoholic fatty liver disease (NAFLD). We reviewed the published literature that reported prevalence, severity, and genetic associations of NAFLD in different ethnic groups. The metabolic syndrome (MetS) has been associated with NAFLD, but each component of the MetS is present in various races in different percentages and their effect on NAFLD appears to be dissimilar. An elevated triglyceride (TG) level seems to have the strongest association with NAFLD. The latter is more prevalent in Hispanic patients; Blacks have lower TG levels and a lower NAFLD prevalence, compared to Caucasians or Hispanics. The severity of liver fibrosis is lower in some, but not all biopsy-based studies of Black patients. No study has evaluated the severity of liver disease controlling for the individual components of MetS, especially TG. Important racial differences in the prevalence of selected genetic polymorphisms, particularly PNPLA-3 and MBOAT7 have been documented, together with their effects on the prevalence of liver steatosis and fibrosis. Data on overall and liver mortality have found no significant differences according to race/ethnicity, with the possible exception of one paper reporting lower cirrhosis mortality in Black patients. We conclude that NAFLD is more prevalent in Hispanics and less in Blacks. This is supported by differences in key genetic polymorphisms associated with hepatic fat storage. However, there is presently insufficient evidence to firmly conclude that race, per se, plays a role in the development of liver fibrosis and its complications. Further studies, appropriately controlled for diet, exercise, and individual MetS parameters are needed.
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Affiliation(s)
- Maurizio Bonacini
- Department of Gastroenterology and Hepatology, California Pacific Medical Center, California Pacific Medical Center, San Francisco, CA 94115, United States.
| | - Farah Kassamali
- Department of Gastroenterology and Hepatology, California Pacific Medical Center, San Francisco, CA 94115, United States
| | - Swathi Kari
- Department of Internal Medicine, St. Mary's medical Center, San Francisco, CA 94117, United States
| | | | - Mohamed Kohla
- Department of Hepatology, National Liver Institute, Menoufiya University, Shibin Al Kom 32511, Menoufiya, Egypt
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12
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Gao S, Ramen K, Yu S, Luo J. Higher non-HDL-cholesterol to HDL-cholesterol ratio is linked to increase in non-alcoholic fatty liver disease: secondary analysis based on a longitudinal study. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2020; 13:2569-2575. [PMID: 33165444 PMCID: PMC7642706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 09/15/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Non-high-density lipoprotein cholesterol (non-HDLc) to HDLc ratio (non-HDLc/HDLc), is a viable predictor of metabolic syndrome, insulin resistance, and other cardiac diseases. The study aimed to assess whether non-HDLC/HDLc ratio is an independent predictor of NAFLD. METHODS The present study was a longitudinal study, involving 16173 Chinese men and women, aging 14-95 years old, who received a medical check-up program in a health examination Center in China. A total of 16173 initially NAFLD-free non-obese individuals were included, who completed a 5-year follow-up examination in the longitudinal study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Univariate and multivariate Cox proportional hazards analyses were used to assess the association between nonHDLC/HDLc and NAFLD. ROC curve analysis was performed to compare the predictive value between the nonHDLc/HDLc and the nonHDLc for NAFLD. RESULTS During the five-year follow-up period, a total of 2322 participants (14.4%) developed NAFLD. The HRs for NAFLD in the longitudinal population were 1.3 (95% CI 1.1 to 1.7) and 1.5 (95% CI 1.1 to 2.0) compared with Q1. AUC values for nonHDLc/HDLc ratios (0.705) were significantly higher than nonHDLc (0.656) (P<0.05), while the cut-off value for the detection of NAFLD was 2.26. Individuals with higher nonHDLc/HDLc ratio had an increased cumulative incidence rate of NAFLD in non-obese individuals. CONCLUSION The Non-HDLc ratio/HDLc is an independent predictor of NAFLD. This may help with early identification of high-risk individuals.
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Affiliation(s)
- Shengqiang Gao
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of MedicineJinhua 321000, Zhejiang, P. R. China
| | - Kuvaneshan Ramen
- Department of Hepatobiliary and Pancreatic Surgery, Private Medical PractitionerMauritius
| | - Shian Yu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of MedicineJinhua 321000, Zhejiang, P. R. China
| | - Jiansheng Luo
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of MedicineJinhua 321000, Zhejiang, P. R. China
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Saiman Y, Hooks R, Carr RM. High-Risk Groups for Non-alcoholic Fatty Liver and Non-alcoholic Steatohepatitis Development and Progression. ACTA ACUST UNITED AC 2020. [DOI: 10.1007/s11901-020-00539-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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14
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Zou ZY, Wong VWS, Fan JG. Epidemiology of nonalcoholic fatty liver disease in non-obese populations: Meta-analytic assessment of its prevalence, genetic, metabolic, and histological profiles. J Dig Dis 2020; 21:372-384. [PMID: 32369237 DOI: 10.1111/1751-2980.12871] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 04/10/2020] [Accepted: 04/28/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVE As a subgroup of nonalcoholic fatty liver disease (NAFLD), patients with non-obese NAFLD may also have an increased risk of adverse hepatic and metabolic outcomes. We aimed to estimate the prevalence and incidence of non-obese NAFLD and to describe its clinical characteristics in this systematic review and meta-analysis. METHODS We performed a systematic search of 1235 citations published up to Mar 2020. Meta-analyses, stratified analyses and meta-regression were all performed. RESULTS Of the 46 studies included, 28 cross-sectional and longitudinal studies of 155 846 non-obese participants reported a pooled NAFLD prevalence of 14.5% (95% confidence interval [CI] 12.3%-17.1%). A multivariate meta-regression analysis showed the trend that the prevalence varied by their geographical location. Further stratified analyses showed that NAFLD was relatively prevalent among people aged ≥45 years (16.2%; 95% CI 10.8-23.4) and those in South America (25.7%; 95% CI 24.4-27.0). The PNPLA3 rs738409 gene polymorphism was more frequently observed in non-obese NAFLD than in both obese NAFLD and non-obese controls, while the metabolic profiles of non-obese NAFLD were less severe than those of the obese NAFLD group. Patients with non-obese NAFLD had 4.81-fold and 5.43-fold higher risk of diabetes mellitus and metabolic syndrome, respectively, than the non-obese controls. CONCLUSIONS Non-obese NAFLD is common, particularly in South America and among people aged ≥45 years. Metabolic diseases and PNPLA3 rs738409 gene polymorphism are more frequent in the non-obese NAFLD group than in non-obese controls.
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Affiliation(s)
- Zi Yuan Zou
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jian Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China
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15
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The Prevalence of Lean/Nonobese Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2020; 54:378-387. [PMID: 31651571 DOI: 10.1097/mcg.0000000000001270] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM The prevalence of lean/nonobese nonalcoholic fatty liver disease (NAFLD) ranges widely in studies. Thus, here, we aimed to perform a meta-analysis on NAFLD prevalence in the lean or nonobese population to give clarity. MATERIALS AND METHODS PubMed, Embase, and the Cochrane Library databases were systematically searched to identify studies reporting NAFLD prevalence in the lean/nonobese population. Lean or nonobese was defined by body mass index cutoffs reported by authors in original studies. NAFLD prevalence based on community, population, or health checkups was combined with random-effect model after logit transformation. Subgroup analysis and meta-regression were further performed to investigate the heterogenicity. RESULTS A total of 45 studies were enrolled in the final analysis, with 55,936 lean/nonobese subjects included, among whom 7351 NAFLD patients were diagnosed. Overall, the pooled NAFLD prevalence of the lean or nonobese population was 10.2% (95% confidence interval: 7.6%-13.6%) and 15.7% (95% confidence interval: 12.5%-19.6%), respectively. Compared with western studies, the NAFLD prevalence in the lean or nonobese population was lower in eastern studies. In addition, the NAFLD prevalence in both the lean and nonobese population showed a general upward trend during recent years. The prevalence was similar in community-based and health checkup-based studies. Lean/nonobese NAFLD patients had significantly lower rates of hypertension, lower uric acid and fasting plasma glucose, and a higher level of high-density lipoprotein than nonlean/obese patients. CONCLUSIONS The prevalence of NAFLD in the lean/nonobese population is not rare in either the western or eastern regions of the world. This meta-analysis of prevalence assessment and clinical characteristics should enable higher confidence in more specific interventions and health care standards for these patients.
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Khneizer G, Rizvi S, Gawrieh S. Non-alcoholic Fatty Liver Disease and Diabetes Mellitus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1307:417-440. [PMID: 32424494 DOI: 10.1007/5584_2020_532] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.
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Affiliation(s)
- Gebran Khneizer
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Syed Rizvi
- A&M College of Medicine, Round Rock, Austin, TX, USA
| | - Samer Gawrieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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Chung ST, Cravalho CKL, Meyers AG, Courville AB, Yang S, Matthan NR, Mabundo L, Sampson M, Ouwerkerk R, Gharib AM, Lichtenstein AH, Remaley AT, Sumner AE. Triglyceride Paradox Is Related to Lipoprotein Size, Visceral Adiposity and Stearoyl-CoA Desaturase Activity in Black Versus White Women. Circ Res 2019; 126:94-108. [PMID: 31623522 DOI: 10.1161/circresaha.119.315701] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
RATIONALE In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index. OBJECTIVE In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels. METHODS AND RESULTS In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m2, we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P=0.001). Black women had smaller postprandial changes in large (P=0.005) and medium TRLPs (P=0.007). CONCLUSIONS Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.
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Affiliation(s)
- Stephanie T Chung
- From the Intramural Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (S.T.C., C.K.L.C., L.M., R.O., A.M.G., A.E.S.)
| | - Celeste K L Cravalho
- From the Intramural Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (S.T.C., C.K.L.C., L.M., R.O., A.M.G., A.E.S.)
| | - Abby G Meyers
- Intramural Program of National Institute of Child Health and Development, National Institutes of Health, MD (A.G.M.)
| | | | - Shanna Yang
- NIH Clinical Center, Bethesda, MD (A.B.C., S.Y.)
| | - Nirupa Rachel Matthan
- Cardiovascular Nutrition Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA (N.R.M., A.H.L.)
| | - Lilian Mabundo
- From the Intramural Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (S.T.C., C.K.L.C., L.M., R.O., A.M.G., A.E.S.)
| | - Maureen Sampson
- National Heart, Lung, and Blood Institute, Bethesda, MD (M.S., A.T.R.)
| | - Ronald Ouwerkerk
- From the Intramural Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (S.T.C., C.K.L.C., L.M., R.O., A.M.G., A.E.S.)
| | - Ahmed M Gharib
- From the Intramural Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (S.T.C., C.K.L.C., L.M., R.O., A.M.G., A.E.S.)
| | - Alice H Lichtenstein
- Cardiovascular Nutrition Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA (N.R.M., A.H.L.)
| | - Alan T Remaley
- National Heart, Lung, and Blood Institute, Bethesda, MD (M.S., A.T.R.)
| | - Anne E Sumner
- From the Intramural Program of National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (S.T.C., C.K.L.C., L.M., R.O., A.M.G., A.E.S.).,National Institute of Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD (A.E.S.)
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Thompson DS, Tennant IA, Soares DP, Osmond C, Byrne CD, Forrester TE, Boyne MS. Nonalcoholic Fatty Liver Disease in Nonobese Subjects of African Origin Has Atypical Metabolic Characteristics. J Endocr Soc 2019; 3:2051-2063. [PMID: 31637346 PMCID: PMC6795019 DOI: 10.1210/js.2019-00138] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 08/15/2019] [Indexed: 12/11/2022] Open
Abstract
Background Nonobese nonalcoholic fatty liver disease is reported in several populations. However, because persons of African origin display unique fat accumulation, insulin resistance, and lipid profiles, we investigated fatty liver in nonobese persons of African origin. Method We recruited 78 urban Jamaican volunteers. CT was used to estimate liver and abdominal fat and dual-energy X-ray absorptiometry to measure body composition. Fasting blood was collected for lipids, alanine aminotransferase (ALT), adiponectin, and fetuin-A. Homeostatic model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), insulinogenic index (IGI), and oral disposition index (oDI) were calculated after a 75-g oral glucose tolerance test. Results Fifty-two percent of participants were male; mean (±SD) age was 28.5 ± 7.8 years, and body mass index was 22.4 ± 3.0 kg/m2. Mean liver attenuation (MLA) and liver/spleen (LS) ratio, both inversely correlated to liver fat, were 62.8 ± 4.3 HU and 1.2 ± 0.1, respectively; 3.8% of participants had liver fat >30% (LS ratio < 1). In age, sex, and BMI-adjusted correlations, MLA was negatively associated with weight (r = −0.30; P = 0.009) and height (r = −0.28; P = 0.017) and was associated with fasting glucose (r = 0.23; P = 0.05), fasting insulin (r = 0.42; P ≤ 0.001) and HOMA-IR (r = 0.35; P = 0.004). Serum lipids, ALT, adiponectin, fetuin-A, WBISI, IGI, and oDI were not associated with liver fat. Conclusions In nonobese Afro-Caribbean participants, greater liver fat was associated with weight and height and lower fasting insulin and hyperinsulinemia appears to be influential in the reduction of NAFLD. These findings may be influenced by ethnicity, body size, and method of estimating liver fat.
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Affiliation(s)
- Debbie S Thompson
- Caribbean Institute for Health Research, The University of the West Indies, Kingston, Jamaica
| | - Ingrid A Tennant
- Caribbean Institute for Health Research, The University of the West Indies, Kingston, Jamaica.,Department of, Surgery, Radiology, Anesthesia and Intensive Care, The University of the West Indies, Kingston, Jamaica
| | - Deanne P Soares
- Department of, Surgery, Radiology, Anesthesia and Intensive Care, The University of the West Indies, Kingston, Jamaica
| | - Clive Osmond
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom
| | - Chris D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.,Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, United Kingdom
| | - Terrence E Forrester
- Caribbean Institute for Health Research, The University of the West Indies, Kingston, Jamaica
| | - Michael S Boyne
- Caribbean Institute for Health Research, The University of the West Indies, Kingston, Jamaica.,Department of Medicine, The University of the West Indies, Kingston, Jamaica
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Szanto KB, Li J, Cordero P, Oben JA. Ethnic differences and heterogeneity in genetic and metabolic makeup contributing to nonalcoholic fatty liver disease. Diabetes Metab Syndr Obes 2019; 12:357-367. [PMID: 30936733 PMCID: PMC6430068 DOI: 10.2147/dmso.s182331] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Obesity is the most prevalent noncommunicable disease in the 21st century, associated with triglyceride deposition in hepatocytes leading to nonalcoholic fatty liver disease (NAFLD). NAFLD is now present in around a third of the world's population. Epidemiological studies have concluded that ethnicity plays a role in complications and treatment response. However, definitive correlations of ethnicity with NAFLD are thoroughly under-reported. A comprehensive review was conducted on ethnic variation in NAFLD patients and its potential role as a crucial effector in complications and treatment response. The highest NAFLD prevalence is observed in Hispanic populations, exhibiting a worse disease progression. In contrast, African-Caribbeans exhibit the lowest risk, with less severe steatosis and inflammation, lower levels of triglycerides, and less metabolic derangement, but conversely higher prevalence of insulin resistance. The prevalence of NAFLD in Asian cohorts is under-reported, although reaching epidemic proportions in these populations. The most well-documented NAFLD patient population is that of Caucasian ethnicity, especially from the US. The relative paucity of available literature suggests there is a vital need for more large-scale multi-ethnic clinical cohort studies to determine the incidence of NAFLD within ethnic groups. This would improve therapy and drug development, as well as help identify candidate gene mutations which may differ within the population based on ethnic background.
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Affiliation(s)
- Krisztina B Szanto
- Faculty of Life Sciences and Medicine, School of Medicine, King's College London, London, UK,
- Institute for Liver and Digestive Health, University College London, London, UK,
| | - Jiawei Li
- Institute for Liver and Digestive Health, University College London, London, UK,
- Institute of Child Health, University College London, London, UK
| | - Paul Cordero
- Institute for Liver and Digestive Health, University College London, London, UK,
| | - Jude A Oben
- Institute for Liver and Digestive Health, University College London, London, UK,
- Department of Gastroenterology and Hepatology, Guy's and St Thomas' Hospital, NHS Foundation Trust, London, UK
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20
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Fernandes DM, Pantangi V, Azam M, Salomao M, Iuga AC, Lefkowitch JH, Gill J, Morotti R, Lavine JE, Mencin AA. Pediatric Nonalcoholic Fatty Liver Disease in New York City: An Autopsy Study. J Pediatr 2018; 200:174-180. [PMID: 29903531 DOI: 10.1016/j.jpeds.2018.04.047] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 03/26/2018] [Accepted: 04/20/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To assess the prevalence and severity of nonalcoholic liver disease (NAFLD) in children in a diverse population sample in New York City. STUDY DESIGN Liver specimens were examined from children 2-19 years old who died of unexpected causes within 48 hours of medical presentation and underwent autopsy in New York City from 2005 to 2010. Records were reviewed for age, sex, weight, height, and race. Two hepatopathologists evaluated each liver specimen to determine pathologic diagnosis. RESULTS The final study cohort (n = 582) was 50% black, 33% Hispanic, 12% white, 3% Asian, and 2% other; 36% had a body mass index >85%. There were 26 cases of NAFLD (4.5%) of which 10 had nonalcoholic steatohepatitis (1.7%). There were no cases with severe fibrosis or cirrhosis. One percent (3/290) of black children had NAFLD and none had nonalcoholic steatohepatitis. White and Hispanic children had the highest percentages of NAFLD at 8.3% and 7.9%, respectively. In multiple logistic regression models, we observed that body mass index z-score (P < .001) was associated with NAFLD, and that white (P = .003) and Hispanic (P = .005) children had higher odds of having NAFLD compared with black children. CONCLUSIONS This review of liver tissue demonstrates a lower prevalence and severity of NAFLD in black children compared with the general obese pediatric population. Hispanic children did not have a significantly increased rate of NAFLD compared with white children, most likely related to the large proportion of Caribbean Hispanic children in New York City.
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Affiliation(s)
| | | | - Muhammad Azam
- St. George's University Hospital, London, United Kingdom
| | | | - Alina C Iuga
- Columbia University Medical Center, New York, NY
| | | | - James Gill
- Office of the Chief Medical Examiner, Farmington, CT
| | | | | | - Ali A Mencin
- Columbia University Medical Center, New York, NY.
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Sanyal AJ. Putting non-alcoholic fatty liver disease on the radar for primary care physicians: how well are we doing? BMC Med 2018; 16:148. [PMID: 30139362 PMCID: PMC6108106 DOI: 10.1186/s12916-018-1149-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 08/06/2018] [Indexed: 02/07/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as a common cause of liver-related morbidity and mortality. Tackling this condition at a societal level will require a clear understanding of the burden of disease in the general population. However, a major limitation of such an assessment, particularly in a real-world setting, is the low rate of diagnosis of the condition, as recently identified by Alexander et al. (BMC Med 16:130, 2018). Therein, the likelihood that the condition is indeed underdiagnosed and the potential causes for such underdiagnosis are discussed. The authors underscore the need for physician education and for development of simple evaluation tools that are both robust and implementable in a primary care setting, along with effective therapeutics to overcome this apathy towards NAFLD. Importantly, there remains a need for additional data on the prevalence of non-alcoholic steatohepatitis, the more aggressive form of NAFLD, especially with progressive fibrosis, along with patient outcomes to inform health policy decisions related to screening, surveillance, and access to therapeutics.
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Affiliation(s)
- Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA. .,Medicine, Physiology and Molecular Pathology, MCV Box 980341, Richmond, VA, 23298-0341, USA.
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22
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Pickett-Blakely O, Young K, Carr RM. Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis. Cell Mol Gastroenterol Hepatol 2018; 6:451-462. [PMID: 30294653 PMCID: PMC6170520 DOI: 10.1016/j.jcmgh.2018.07.004] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 07/19/2018] [Indexed: 02/06/2023]
Abstract
Micronutrients include electrolytes, minerals, vitamins, and carotenoids, and are required in microgram or milligram quantities for cellular metabolism. The liver plays an important role in micronutrient metabolism and this metabolism often is altered in chronic liver diseases. Here, we review how the liver contributes to micronutrient metabolism; how impaired micronutrient metabolism may be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a systemic disorder of energy, glucose, and lipid homeostasis; and how insights gained from micronutrient biology have informed NAFLD therapeutics. Finally, we highlight some of the challenges and opportunities that remain with investigating the contribution of micronutrients to NAFLD pathology and suggest strategies to incorporate our understanding into the care of NAFLD patients.
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Affiliation(s)
| | | | - Rotonya M. Carr
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
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Soti S, Corey KE, Lake JE, Erlandson KM. NAFLD and HIV: Do Sex, Race, and Ethnicity Explain HIV-Related Risk? Curr HIV/AIDS Rep 2018; 15:212-222. [PMID: 29671204 PMCID: PMC6003864 DOI: 10.1007/s11904-018-0392-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Here, we review the epidemiology, diagnosis, and management of non-alcoholic fatty liver disease (NAFLD) in the general population, discuss HIV-specific differences in NAFLD pathogenesis, and summarize what is known regarding differences in NAFLD by race/ethnicity and sex. RECENT FINDINGS The reported prevalence of NAFLD among people living with HIV varies by age, body mass index, comorbidity, and method of NAFLD diagnosis, but is generally thought to be greater among HIV-infected compared to HIV-uninfected populations. Minorities and women tend to experience poorer HIV treatment outcomes (Meditz et al. J Infect Dis. 203(4):442-51, 2011; Beer et al. Medicine (Baltimore). 95(13):e 3171, 2016; Gant et al. MMWR Morb Mortal Wkly Rep. 66(40):1065-72, 2017; Millett et al. Lancet. 380(9839):341-8, 2012; Wejnert et al. J Infect Dis. 213(5):776-83, 2016), and are at the greatest risk for significant weight gain with HIV treatment (Erlandson et al. Medicine (Baltimore). 95(46):e 5399, 2016). Thus, women and minorities living with HIV may be at a higher risk of developing NAFLD and progressive liver disease. Disparities in the diagnosis, progression, and prognosis of NAFLD and HIV-associated NAFLD may be, in part, explained by genetic and sex differences; however, data is limited.
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Affiliation(s)
- Subada Soti
- School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA
| | - Kathleen E Corey
- Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Jordan E Lake
- University of Texas Health Sciences Center, Houston, TX, USA
| | - Kristine M Erlandson
- Department of Medicine, Division of Infectious Diseases, University of Colorado-Anschutz Medical Campus, 12700 E. 19th Avenue, Mail Stop B168, Aurora, CO, 80045, USA.
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24
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Younossi ZM, Henry L, Bush H, Mishra A. Clinical and Economic Burden of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Clin Liver Dis 2018; 22:1-10. [PMID: 29128049 DOI: 10.1016/j.cld.2017.08.001] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with an increasing global prevalence associated with tremendous clinical, economic, and health-related quality-of-life burden. Clinically, NAFLD is considered the liver manifestation of metabolic syndrome. However, diagnosing NAFLD presents significant challenges due to the limited noninvasive and accurate diagnostic tools available to not only accurately diagnose nonalcoholic steatohepatitis but also to stage hepatic fibrosis, the major predictor of long-term outcomes, including mortality.
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Affiliation(s)
- Zobair M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA.
| | - Linda Henry
- Center for Outcomes Research in Liver Disease, 2411 I Street NW, Washington, DC 20037, USA
| | - Haley Bush
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, 3300 Gallows Road, Falls Church, VA 22042, USA
| | - Alita Mishra
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA
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Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15:11-20. [PMID: 28930295 DOI: 10.1038/nrgastro.2017.109] [Citation(s) in RCA: 3719] [Impact Index Per Article: 531.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
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Affiliation(s)
- Zobair Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, Virginia 22042, USA
- Center for Outcomes Research in Liver Disease, 2411 I Street NW, Washington DC, 20037, USA
| | - Quentin M Anstee
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4 th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
- Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne, NE7 7DN, UK
| | - Milena Marietti
- Division of Gastroenterology, Department of Medical Sciences, University of Torino, AOU Città della Salute e della Scienza, Corso Dogliotti 14, 10126 Torino, Italy
| | - Timothy Hardy
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, 4 th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
- Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne, NE7 7DN, UK
| | - Linda Henry
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, Virginia 22042, USA
- Center for Outcomes Research in Liver Disease, 2411 I Street NW, Washington DC, 20037, USA
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, 176 Hawkesbury Rd, Westmead NSW 2145, Sydney, New South Wales, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, 176 Hawkesbury Rd, Westmead NSW 2145, Sydney, New South Wales, Australia
| | - Elisabetta Bugianesi
- Division of Gastroenterology, Department of Medical Sciences, University of Torino, AOU Città della Salute e della Scienza, Corso Dogliotti 14, 10126 Torino, Italy
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26
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Kliethermes S, Ma M, Purtell C, Balasubramanian N, Gonzalez B, Layden TJ, Cotler SJ. An assessment of racial differences in the upper limits of normal ALT levels in children and the effect of obesity on elevated values. Pediatr Obes 2017; 12:363-372. [PMID: 27237782 DOI: 10.1111/ijpo.12152] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 12/29/2015] [Accepted: 04/18/2016] [Indexed: 01/23/2023]
Abstract
OBJECTIVES Childhood obesity is a risk factor for non-alcoholic fatty liver disease and poses important public health issues for children. Racial differences in alanine aminotransferase (ALT) levels among children have not been described. This study aimed to identify racial differences in upper limit normal (ULN) ALT levels and evaluate the effect of obesity on elevated levels in children without other metabolic risk factors. METHODS National Health and Nutrition Examination Surveys and clinical data from the Loyola University Health System were used to determine ULN ALT by race and gender. Quantile regression was used to evaluate the impact of obesity on elevated ALT and to identify potential risk factors for ALT above the ULN. RESULTS Upper limit normal (ULN) ALT was approximately 28.0 and 21.0-24.0 U/L for boys and girls, respectively. No significant difference in ULN ALT across race was observed. Obesity was significantly associated with elevated ALT; obese children with elevated ALT had values 10 U/L higher than normal-weight children. CONCLUSIONS Racial differences in ALT levels among adults are not evident in children. Obesity, in the absence of metabolic risk factors and other causes of liver disease, is associated with elevated ALT, providing evidence against the concept of healthy obesity in children.
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Affiliation(s)
- S Kliethermes
- Department of Medicine, Section of Hepatology, Loyola University Chicago, Maywood, IL, USA.,Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, USA
| | - M Ma
- Department of Pediatrics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - C Purtell
- Department of Pediatrics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - N Balasubramanian
- Department of Medicine, Section of Hepatology, Loyola University Chicago, Maywood, IL, USA
| | - B Gonzalez
- Department of Medicine, Section of Hepatology, Loyola University Chicago, Maywood, IL, USA
| | - T J Layden
- Department of Medicine, Section of Hepatology, Loyola University Chicago, Maywood, IL, USA
| | - S J Cotler
- Department of Medicine, Section of Hepatology, Loyola University Chicago, Maywood, IL, USA
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Chalasani N, Reddy KRK, Fontana RJ, Barnhart H, Gu J, Hayashi PH, Ahmad J, Stolz A, Navarro V, Hoofnagle JH. Idiosyncratic Drug Induced Liver Injury in African-Americans Is Associated With Greater Morbidity and Mortality Compared to Caucasians. Am J Gastroenterol 2017; 112:1382-1388. [PMID: 28762375 PMCID: PMC5667647 DOI: 10.1038/ajg.2017.215] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Accepted: 05/01/2017] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Idiosyncratic drug induced liver injury (DILI) is a rare but potentially serious liver disorder and a major cause of significant liver injury. Limited data exist on racial differences in DILI incidence, presentation, and course. METHODS We compared the causative agents, clinical features, and outcomes of DILI among self-described African-Americans and non-Hispanic whites (Caucasians) enrolled in the DILIN Prospective Study. Individuals with definite, highly likely, or probable DILI enrolled between September 2004 and February 2016 were included in this analysis. RESULTS 144 African-Americans and 841 Caucasian patients met the eligibility criteria. Causal medications varied by race: trimethoprim/sulfamethoxazole being the most common cause among African-Americans (7.6 vs. 3.6%) followed by methyldopa (4 vs. <1%), phenytoin (5 vs. <1%), isoniazid (4 vs. 4%), and amoxicillin/clavulanate (4.1 vs. 13.4%). The severity of illness, however, tended to be greater in African-Americans than Caucasians as determined by peak mean bilirubin (14.3 vs. 12.8 mg/dl), INR (1.9 vs. 1.6), and DILIN severity score (3.0 vs. 2.6). The frequency of severe cutaneous reactions was significantly higher in African-Americans (2.1 vs. 0.36% in Caucasians, P=0.048). African-Americans also had higher rates of hospitalization (76.7 vs. 57.6%, P<0.001), liver transplantation or liver related death by 6 months (10.2 vs. 5.8%, P=0.02 after controlling for selected covariates), and chronic DILI (24 vs. 16%, P=0.06). CONCLUSIONS The most common DILI causative agents differ between African-Americans and Caucasians. African-Americans are more likely to have severe cutaneous reactions and more severe liver injury leading to worse outcomes, including death and liver transplant.
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Affiliation(s)
| | | | | | | | - Jiezhun Gu
- University of North Carolina, Chapel Hill, NC
| | | | - Jawad Ahmad
- University of Southern California, Los Angeles, CA
| | | | - Victor Navarro
- Liver Diseases Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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28
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Vreman RA, Goodell AJ, Rodriguez LA, Porco TC, Lustig RH, Kahn JG. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model. BMJ Open 2017; 7:e013543. [PMID: 28775179 PMCID: PMC5577881 DOI: 10.1136/bmjopen-2016-013543] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 06/20/2017] [Accepted: 06/21/2017] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVES Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. METHODS Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015-2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. FINDINGS The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. CONCLUSIONS The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits.
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Affiliation(s)
- Rick A Vreman
- Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, California, USA
| | - Alex J Goodell
- Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, California, USA
| | - Luis A Rodriguez
- Department of Epidemiology & Biostatistics, University of California, San Francisco, California, USA
| | - Travis C Porco
- Department of Epidemiology & Biostatistics, University of California, San Francisco, California, USA
- FI Proctor Foundation for Research in Ophthalmology, University of California, San Francisco, California, USA
| | - Robert H Lustig
- Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, California, USA
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
| | - James G Kahn
- Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, California, USA
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Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk. Adv Ther 2017; 34:1291-1326. [PMID: 28526997 PMCID: PMC5487879 DOI: 10.1007/s12325-017-0556-1] [Citation(s) in RCA: 394] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatis, cirrhosis, and hepatocellular carcinoma (HCC) associated with striking systemic features and excess cardiovascular and liver-related mortality. The pathogenesis of NAFLD is complex and multifactorial. Endocrine derangements are closely linked with dysmetabolic traits. For example, in animal and human studies, female sex is protected from dysmetabolism thanks to young individuals' ability to partition fatty acids towards ketone body production rather than very low density lipoprotein (VLDL)-triacylglycerol, and to sex-specific browning of white adipose tissue. Ovarian senescence facilitates both the development of massive hepatic steatosis and the fibrotic progression of liver disease in an experimental overfed zebrafish model. Consistently, estrogen deficiency, by potentiating hepatic inflammatory changes, hastens the progression of disease in a dietary model of nonalcoholic steatohepatitis (NASH) developing in ovariectomized mice fed a high-fat diet. In humans, NAFLD more often affects men; and premenopausal women are equally protected from developing NAFLD as they are from cardiovascular disease. It would be expected that early menarche, definitely associated with estrogen activation, would produce protection against the risk of NAFLD. Nevertheless, it has been suggested that early menarche may confer an increased risk of NAFLD in adulthood, excess adiposity being the primary culprit of this association. Fertile age may be associated with more severe hepatocyte injury and inflammation, but also with a decreased risk of liver fibrosis compared to men and postmenopausal status. Later in life, ovarian senescence is strongly associated with severe steatosis and fibrosing NASH, which may occur in postmenopausal women. Estrogen deficiency is deemed to be responsible for these findings via the development of postmenopausal metabolic syndrome. Estrogen supplementation may at least theoretically protect from NAFLD development and progression, as suggested by some studies exploring the effect of hormonal replacement therapy on postmenopausal women, but the variable impact of different sex hormones in NAFLD (i.e., the pro-inflammatory effect of progesterone) should be carefully considered.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena, Pavullo Hospital, Pavullo nel Frignano, Italy
| | - Fabio Nascimbeni
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Marrazzo
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Dante Romagnoli
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Amedeo Lonardo
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
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Adejumo AC, Alliu S, Ajayi TO, Adejumo KL, Adegbala OM, Onyeakusi NE, Akinjero AM, Durojaiye M, Bukong TN. Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study. PLoS One 2017; 12:e0176416. [PMID: 28441459 PMCID: PMC5404771 DOI: 10.1371/journal.pone.0176416] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 04/09/2017] [Indexed: 12/24/2022] Open
Abstract
Cannabis use is associated with reduced prevalence of obesity and diabetes mellitus (DM) in humans and mouse disease models. Obesity and DM are a well-established independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most prevalent liver disease globally. The effects of cannabis use on NAFLD prevalence in humans remains ill-defined. Our objective is to determine the relationship between cannabis use and the prevalence of NAFLD in humans. We conducted a population-based case-control study of 5,950,391 patients using the 2014 Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Survey (NIS) discharge records of patients 18 years and older. After identifying patients with NAFLD (1% of all patients), we next identified three exposure groups: non-cannabis users (98.04%), non-dependent cannabis users (1.74%), and dependent cannabis users (0.22%). We adjusted for potential demographics and patient related confounders and used multivariate logistic regression (SAS 9.4) to determine the odds of developing NAFLD with respects to cannabis use. Our findings revealed that cannabis users (dependent and non-dependent) showed significantly lower NAFLD prevalence compared to non-users (AOR: 0.82[0.76-0.88]; p<0.0001). The prevalence of NAFLD was 15% lower in non-dependent users (AOR: 0.85[0.79-0.92]; p<0.0001) and 52% lower in dependent users (AOR: 0.49[0.36-0.65]; p<0.0001). Among cannabis users, dependent patients had 43% significantly lower prevalence of NAFLD compared to non-dependent patients (AOR: 0.57[0.42-0.77]; p<0.0001). Our observations suggest that cannabis use is associated with lower prevalence of NAFLD in patients. These novel findings suggest additional molecular mechanistic studies to explore the potential role of cannabis use in NAFLD development.
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Affiliation(s)
- Adeyinka Charles Adejumo
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
- Biomedical Engineering & Biotechnology Program, University of Massachusetts Lowell, Lowell Massachusetts, United States of America
| | - Samson Alliu
- Department of Medicine, Maimonides Medical Center, Brooklyn, New York, United States of America
| | - Tokunbo Opeyemi Ajayi
- Johns Hopkins Medicine, Howard County General Hospital, Columbia, Maryland, United States of America
| | | | - Oluwole Muyiwa Adegbala
- Department of Medicine, Englewood Hospital and Medical Center, Englewood, New Jersey, United States of America
| | | | - Akintunde Micheal Akinjero
- Department of Medicine, Englewood Hospital and Medical Center, Englewood, New Jersey, United States of America
| | - Modupeoluwa Durojaiye
- Department of Maternal and Child Health, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
| | - Terence Ndonyi Bukong
- Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
- INRS-Institut Armand-Frappier, Institut National de la Reserche Scientifique, Laval, Quebec, Canada
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31
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Kim D, Kim WR. Nonobese Fatty Liver Disease. Clin Gastroenterol Hepatol 2017; 15:474-485. [PMID: 27581063 DOI: 10.1016/j.cgh.2016.08.028] [Citation(s) in RCA: 258] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 08/22/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) refers to a group of conditions characterized by hepatic steatosis in the absence of significant alcohol consumption. NAFLD is seen commonly in patients with metabolic abnormalities associated with obesity, such as type II diabetes, dyslipidemia, and metabolic syndrome. Evidently, however, not all obese subjects develop NAFLD and, more importantly, NAFLD can be found in nonobese individuals. Although NAFLD occurring in nonobese subjects has been reported in children and adults of all ethnicities, it appears to be recognized more frequently in Asians, even when strict ethnicity-specific body mass index criteria are used to define obesity. Studies based on liver biopsies suggest that the prevalence of nonalcoholic steatohepatitis and fibrosis does not differ significantly between nonobese NAFLD and NAFLD in obese patients. Visceral obesity as opposed to general obesity, high fructose and cholesterol intake, and genetic risk factors (eg, palatin-like phospholipase domain-containing 3) may be associated with nonobese NAFLD. In general, nonalcoholic steatohepatitis is associated with increased mortality, primarily from cardiovascular causes, independent of other metabolic factors. Although data regarding the mortality impact of nonobese NAFLD are not as mature, it may be important to identify high-risk nonobese NAFLD patients and manage their metabolic profile. Currently, lifestyle modification to reduce visceral adiposity, including dietary changes and physical activity, remains the standard of care in patients with nonobese NAFLD.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
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32
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Hannah WN, Torres DM, Harrison SA. Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials. Gastroenterol Hepatol (N Y) 2016; 12:756-763. [PMID: 28035202 PMCID: PMC5193083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development. The complex molecular mechanisms leading to NASH and the long duration of time to develop complications of disease are challenges to developing meaningful clinical endpoints. Because of these challenges, surrogate endpoints that are linked to all-cause mortality, liver-related death, and complications of cirrhosis are much more likely to be beneficial in the majority of patients.
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Affiliation(s)
- William N Hannah
- Dr Hannah is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Department of Medicine at the San Antonio Military Medical Center in Joint Base San Antonio-Fort Sam Houston, Texas. Dr Torres is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Division of Gastroenterology in the Department of Medicine at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr Harrison is a visiting professor of hepatology in the Radcliffe Department of Medicine at the University of Oxford in Oxford, United Kingdom
| | - Dawn M Torres
- Dr Hannah is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Department of Medicine at the San Antonio Military Medical Center in Joint Base San Antonio-Fort Sam Houston, Texas. Dr Torres is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Division of Gastroenterology in the Department of Medicine at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr Harrison is a visiting professor of hepatology in the Radcliffe Department of Medicine at the University of Oxford in Oxford, United Kingdom
| | - Stephen A Harrison
- Dr Hannah is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Department of Medicine at the San Antonio Military Medical Center in Joint Base San Antonio-Fort Sam Houston, Texas. Dr Torres is an associate professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland and the Division of Gastroenterology in the Department of Medicine at the Walter Reed National Military Medical Center in Bethesda, Maryland. Dr Harrison is a visiting professor of hepatology in the Radcliffe Department of Medicine at the University of Oxford in Oxford, United Kingdom
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Association between nonalcoholic fatty liver disease and coronary artery calcification in postmenopausal women. Menopause 2016; 22:1323-7. [PMID: 26154274 PMCID: PMC4666010 DOI: 10.1097/gme.0000000000000503] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Objective: Cardiovascular disease is a leading cause of death in postmenopausal women, and nonalcoholic fatty liver disease (NAFLD) has been known to be associated with cardiovascular disease. However, little information regarding the relationship between NAFLD and coronary artery calcification (CAC) in postmenopausal women is available. The aim of this study was to investigate the association between NAFLD and CAC in postmenopausal women. Methods: Among 4,377 participants who underwent cardiac computed tomography in a health promotion center, 919 postmenopausal women were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were measured. NAFLD was measured by ultrasonography, and CAC was evaluated by cardiac computed tomography. Odds ratios and 95% CI for the presence of CAC, by severity of fatty liver disease, were estimated using logistic regression. Results: Women were stratified into three groups by severity of NAFLD. There were significant differences in cardiovascular parameters among the groups, and prevalence of CAC significantly increased with severity of NAFLD. On logistic regression analysis after adjustment for multiple risk factors, the odds ratios for the prevalence of CAC were as follows (P < 0.05): no NAFLD, 1.0; mild NAFLD, 1.34 (95% CI, 0.92-2.16); moderate to severe NAFLD, 1.83 (95% CI, 1.06-3.16). However, this association was attenuated after adjustment for insulin resistance (P = 0.16). Conclusions: There is a significant correlation between NAFLD and prevalence of CAC, but NAFLD is not an independent factor for coronary atherosclerosis in postmenopausal women.
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Burton BK. Reply to a Letter to the Editor Regarding the Original Article, Clinical Features of Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2015;61(6): 619-625. J Pediatr Gastroenterol Nutr 2016; 63:e39-40. [PMID: 27035378 DOI: 10.1097/mpg.0000000000001212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Barbara K Burton
- Division of Genetics, Birth Defects, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
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Yun KE, Nam GE, Lim J, Park HS, Chang Y, Jung HS, Kim CW, Ko BJ, Chung EC, Shin H, Ryu S. Waist Gain Is Associated with a Higher Incidence of Nonalcoholic Fatty Liver Disease in Korean Adults: A Cohort Study. PLoS One 2016; 11:e0158710. [PMID: 27420035 PMCID: PMC4946777 DOI: 10.1371/journal.pone.0158710] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 06/21/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We examined the relationship between changes in waist circumference (WC) and the incidence of nonalcoholic fatty liver disease (NAFLD). METHODS A cohort study of 37,130 men and women were followed-up annually or biennially. Differences in WC between baseline and subsequent measurements were categorized in quartiles: first (WC loss), second (no change in WC as the reference), third and highest quartiles (WC gain). The presence of fatty liver was determined using ultrasound. Parametric Cox modeling was used to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) of the incidence of NAFLD. RESULTS During 127,324.4 person-years of follow-up, 6249 participants developed NAFLD. Despite adjusting for possible confounders, the risk of development of NAFLD increased with increasing quartiles of WC change in a dose-response manner (p for trend < 0.001). Compared with the reference, WC loss was associated with a lower risk of NAFLD (men: aHR 0.79 [95% CI: 0.73-0.87]; women: 0.72 [0.63-0.81]), and the highest quartile (WC gain) was associated with a higher risk of NAFLD (men: 1.30 [1.19-1.42]; women: 1.48 [1.31-1.67]). CONCLUSION Waist gain appears to increase the risk of developing NAFLD, independently of the baseline body mass index and WC.
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Affiliation(s)
- Kyung Eun Yun
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Ga Eun Nam
- Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan-si, South Korea
| | - Jisun Lim
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hye Soon Park
- Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Hyun-Suk Jung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Chan-Won Kim
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Byung-Joon Ko
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Eun Chul Chung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea
| | - Hocheol Shin
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
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Olusanya TO, Lesi OA, Adeyomoye AA, Fasanmade OA. Non alcoholic fatty liver disease in a Nigerian population with type II diabetes mellitus. Pan Afr Med J 2016; 24:20. [PMID: 27583084 PMCID: PMC4992392 DOI: 10.11604/pamj.2016.24.20.8181] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Accepted: 12/01/2015] [Indexed: 01/01/2023] Open
Abstract
Introduction Worldwide, Non-alcoholic fatty liver disease (NAFLD) has become an important cause of chronic liver disease and cardiovascular morbidity, even more so in subjects with Type II Diabetes Mellitus (T2DM). The aim of this study was to determine the prevalence and risk factors of NAFLD in an African population with Type II Diabetes Mellitus. Methods We performed a case control study and evaluated anthropometric and biochemical risk factors for NAFLD in 336 subjects (T2DM and non-diabetic controls). Parameters assessed included estimation of BMI (Body Mass Index), measurement of waist circumference (WC), serum cholesterol including HDL-C, LDL-C and triglyceride and serum transaminases (ALT and AST). Hepatitis B and C viral antibody screening was also performed. The diagnosis of NAFLD was confirmed by identification of hepatic steatosis on abdominal ultrasound scan evaluation and exclusion of significant alcohol consumption. Results NAFLD was identified in 16.7% (28 of 168) patients with T2DM compared with 1.2% (2 of 168) non-diabetic controls (Odds Ratio 16.6; p < 0.001). Central obesity (WC > 102cm) and dyslipidaemia (HDL-c < 40mg/dl) were independently associated with NAFLD in male subjects with T2DM (p = 0.03 and p = 0.04 respectively). Conclusion NAFLD occurred more frequently in patients with T2DM than controls and was associated with central obesity and dyslipidaemia. The diabetic subjects with NAFLD will require more intensive therapy to decrease the risk of hepatic, cardiovascular and other adverse events.
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Affiliation(s)
| | | | | | - Olufemi Adetola Fasanmade
- Department of Radiology, Lagos, Nigeria, Faculty of Clinical Sciences, College of Medicine, University of Lagos Teaching Hospital, PMB 12003, Idi-Araba, Lagos Nigeria
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Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the United States and the Rest of the World. Clin Liver Dis 2016; 20:205-14. [PMID: 27063264 DOI: 10.1016/j.cld.2015.10.001] [Citation(s) in RCA: 397] [Impact Index Per Article: 44.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease with increasing prevalence, which can progress to cirrhosis and liver failure. Because of the obesity epidemic and increasing prevalence of metabolic syndrome, NAFLD and its progressive form, nonalcoholic steatohepatitis, are seen more commonly in different parts of the world. This article reviews the worldwide epidemiology of NAFLD and nonalcoholic steatohepatitis. The PubMed database was used to identify studies related to epidemiology of NAFLD in the adult population. It is estimated that the epidemic of obesity will continue to fuel the burden of NAFLD and its long-term complications.
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Thinkhamrop K, Khuntikeo N, Phonjitt P, Chamadol N, Thinkhamrop B, Moore MA, Promthet S. Association between Diabetes Mellitus and Fatty Liver Based on Ultrasonography Screening in the World's Highest Cholangiocarcinoma Incidence Region, Northeast Thailand. Asian Pac J Cancer Prev 2016; 16:3931-6. [PMID: 25987063 DOI: 10.7314/apjcp.2015.16.9.3931] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Fatty liver disease (FLD) can be a precondition for other liver pathology including cholangiocarcinoma (CCA). Diabetes mellitus (DM) has been suggested in some studies to be a risk factor for FLD as well as cancers, including cholangiocellular carcinoma; however, there are currently very few studies on FLD in DM subjects, although the rate of FLD continues to increase annually. To determine the association between DM and FLD ultrasonographic data were analyzed from the Cholangiocarcinoma Screening and Care Program (CASCAP), in northeast Thailand. DM was reported by the subjects based on the CASCAP health questionnaire. Factors that were associated with FLD were determined by prevalence, odds ratio (ORs) and its 95% confidence intervals (CIs) using multiple logistic regression. There were 45,263 subjects with a mean age of 53.46 (±9.25) years. FLD was found in 36.3% of DM subjects but only in 20.7% of non-DM subjects. The association between DM and FLD was adjusted for all other factors including gender, age, education level, relatives diagnosed with CCA, smoking, alcohol consumption, and hepatitis B and C. The risk of DM in subjects having FLD was highly significant compared with the non-DM subjects (OR 2.13; 95%CI: 1.92 to 2.35; p-value < 0.001). Thus DM is significantly associated with FLD which in turn may facilitate the development of several diseases including CCA. DM should be taken into consideration in future ultrasonic investigations of FLD and CCA.
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Affiliation(s)
- Kavin Thinkhamrop
- Doctor of Public Health Program, Faculty of Public Health, Khon Kaen University, Thailand E-mail :
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Saab S, Manne V, Nieto J, Schwimmer JB, Chalasani NP. Nonalcoholic Fatty Liver Disease in Latinos. Clin Gastroenterol Hepatol 2016; 14:5-12; quiz e9-10. [PMID: 25976180 DOI: 10.1016/j.cgh.2015.05.001] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/28/2015] [Accepted: 05/05/2015] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious public health concern that affects almost one third of the US population. The prevalence of NAFLD varies among ethnic/racial groups, with the Latin American population being affected disproportionately. The severity of NAFLD also may be greater in the Latino population. The increased prevalence and severity of NAFLD in Latino Americans likely is related to the interplay between issues such as genetic factors, access to health care, or the prevalence of chronic diseases such as metabolic syndrome or diabetes. In this review, we summarize the current literature on the prevalence and risk factors of NAFLD that are seen to be more common in the Latino population in the United States. Finally, we discuss available treatment options, medical and surgical, that are available for NAFLD and how they affect the Latino population. Health care providers need to address modifiable risk factors that impact the natural history as well as treatment outcomes for NAFLD among Latinos. Additional efforts are needed to improve awareness and health care utilization for Latinos.
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Affiliation(s)
- Sammy Saab
- Division of Digestive Diseases, Departments of Medicine and Surgery, University of California Los Angeles School of Medicine, Los Angeles, California.
| | - Vignan Manne
- Department of Medicine, Akron General Medical Center, Akron, Ohio
| | - Jose Nieto
- Borland-Groover Clinic, Jacksonville, Florida
| | - Jeffrey B Schwimmer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, San Diego, California
| | - Naga P Chalasani
- Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
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Lonardo A, Bellentani S, Argo CK, Ballestri S, Byrne CD, Caldwell SH, Cortez-Pinto H, Grieco A, Machado MV, Miele L, Targher G. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis 2015; 47:997-1006. [PMID: 26454786 DOI: 10.1016/j.dld.2015.08.004] [Citation(s) in RCA: 334] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 07/27/2015] [Accepted: 08/06/2015] [Indexed: 02/07/2023]
Abstract
An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidaemia", "familial heterozygous hypobetalipoproteinaemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to "non-alcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease. A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups.
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Affiliation(s)
- Amedeo Lonardo
- Internal Medicine and Outpatient Liver Clinic, NOCSAE Baggiovara, Azienda USL di Modena, Modena, Italy.
| | - Stefano Bellentani
- Internal Medicine and Outpatient Liver Clinic, NOCSAE Baggiovara, Azienda USL di Modena, Modena, Italy; Department of Gastroenterology and Endoscopy, NOCSE Baggiovara, Azienda USL di Modena Modena, Italy
| | | | - Stefano Ballestri
- Internal Medicine Pavullo Hospital, Azienda USL di Modena, Modena, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, University of Southampton, Southampton National Institute for Health Research Biomedical Research Centre, Southampton, UK
| | | | - Helena Cortez-Pinto
- Department of Gastroenterology, University Hospital of Santa Maria, Faculty of Medicine, Lisbon, Portugal
| | - Antonio Grieco
- Institute of Internal Medicine, Catholic University of Rome, Rome, Italy
| | - Mariana V Machado
- Department of Gastroenterology, University Hospital of Santa Maria, Faculty of Medicine, Lisbon, Portugal
| | - Luca Miele
- Institute of Internal Medicine, Catholic University of Rome, Rome, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
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Pang Q, Zhang JY, Song SD, Qu K, Xu XS, Liu SS, Liu C. Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index. World J Gastroenterol 2015; 21:1650-1662. [PMID: 25663786 PMCID: PMC4316109 DOI: 10.3748/wjg.v21.i5.1650] [Citation(s) in RCA: 131] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Revised: 06/11/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether central obesity is associated with nonalcoholic fatty liver disease (NAFLD) formation after adjusting for general obesity. METHODS The online databases PubMed, EMBASE, and ISI Web of Science were searched for studies estimating the influence of central obesity on NAFLD occurrence published through April 2014. Studies that did not adjust for body mass index (BMI) were excluded. In addition, the independent effect of BMI was also assessed with the included studies. The pooled effect sizes and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the degree of heterogeneity. Furthermore, subgroup analyses, meta-regression, sensitivity analyses, and publication bias were performed. RESULTS Twenty eligible studies were identified. The summary odds ratio (OR) values per-unit increase in waist circumference (WC) and BMI for NAFLD formation were 1.07 (95%CI: 1.03-1.10, I (2) = 73.9%, n = 11 studies) and 1.25 (95%CI: 1.13-1.38, I (2) = 88.7%, n = 11 studies), respectively. When the indices were expressed as binary variables (with the non-obesity group as reference), the pooled OR in WC, waist-to-hip ratio, and BMI were 2.34 (95%CI: 1.83-3.00, I (2) = 41.8%, n = 7 studies), 4.06 (95%CI: 1.53-10.79, I (2) = 65.7%, n = 3 studies), and 2.85 (95%CI: 1.60-5.08, I (2) = 57.8%, n = 5 studies), respectively. Using the same studies as the latter (n = 5), pooled OR in WC was 3.14 (95%CI: 2.07-4.77), which is greater than that in BMI. CONCLUSION Central obesity may pose a greater threat to national health than general obesity, although both are independently associated with increased risk of NAFLD.
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Bertolotti M, Lonardo A, Mussi C, Baldelli E, Pellegrini E, Ballestri S, Romagnoli D, Loria P. Nonalcoholic fatty liver disease and aging: epidemiology to management. World J Gastroenterol 2014; 20:14185-14204. [PMID: 25339806 PMCID: PMC4202348 DOI: 10.3748/wjg.v20.i39.14185] [Citation(s) in RCA: 223] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 02/17/2014] [Accepted: 06/14/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic (nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications (cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment (diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.
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Methotrexate-associated nonalcoholic fatty liver disease with transaminitis in rheumatoid arthritis. ScientificWorldJournal 2014; 2014:823763. [PMID: 24971392 PMCID: PMC4058155 DOI: 10.1155/2014/823763] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Revised: 05/03/2014] [Accepted: 05/17/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. METHODS Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. RESULTS Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512). CONCLUSION The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.
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