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Attanasi ML, Gregoski MJ, Rockey DC. Racial Differences in Liver Fibrosis Burden. Dig Dis Sci 2025:10.1007/s10620-025-08936-w. [PMID: 40102343 DOI: 10.1007/s10620-025-08936-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 02/15/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND & AIMS Liver histology is the classic method for staging the severity of liver fibrosis, which in turn is an important predictor of clinical outcome. Here, we have hypothesized that the susceptibility to develop fibrosis varies among racial groups. METHODS We examined the histology of all patients over 18 years of age who underwent liver biopsy at the Medical University of South Carolina from 1/1/2013 to 7/1/2021. Patients with malignancy, liver metastases, or missing data were excluded. Fibrosis was quantified using the Batts-Ludwig system (F0 = no fibrosis to F4 = histological cirrhosis). Racial groups were propensity matched based on age, gender, diabetes, alcohol consumption, and CDC/ATSDR Social Vulnerability Index Themes to mitigate the risk of selection bias. RESULTS We identified 1101 patients with liver biopsy histological fibrosis scores. The cohort included 23% Black patients. After propensity matching, Black patients were significantly more likely to have Hepatitis C (73/228 (32%) vs 45/228 (20%), p < 0.001) and autoimmune hepatitis (34/228 (15%) vs 6/228 (3%), p < 0.001) than White patients, while White patients were significantly more likely to have metabolic dysfunction associated steatotic liver disease (71/228 (31%) vs 18/228 (8%), p < 0.001). White patients were significantly more likely to have cirrhosis than Black patients (White - 89/228 (39%) vs Black - 68/228 (30%), p < 0.05). CONCLUSION White patients had a greater overall burden of advanced fibrosis (F4/cirrhosis) than Black patients, independent of etiology. The data suggest that fibrosis risk and/or progression may be worse in White than Black patients.
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Affiliation(s)
- Michael L Attanasi
- Department of Internal Medicine, North Shore University Hospital, Manhasset, NY, USA
| | - Mathew J Gregoski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA
| | - Don C Rockey
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, USA.
- Department of Internal Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 803, Charleston, SC, 29425, USA.
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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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Goldberg D, Wilder J, Terrault N. Health disparities in cirrhosis care and liver transplantation. Nat Rev Gastroenterol Hepatol 2025; 22:98-111. [PMID: 39482363 DOI: 10.1038/s41575-024-01003-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2024] [Indexed: 11/03/2024]
Abstract
Morbidity and mortality from cirrhosis are substantial and increasing. Health disparities in cirrhosis and liver transplantation are reflective of inequities along the entire spectrum of chronic liver disease care, from screening and diagnosis to prevention and treatment of liver-related complications. The key populations experiencing disparities in health status and healthcare delivery include racial and ethnic minority groups, sexual and gender minorities, people of lower socioeconomic status and underserved rural communities. These disparities lead to delayed diagnosis of chronic liver disease and complications of cirrhosis (for example, hepatocellular carcinoma), to differences in treatment of chronic liver disease and its complications, and ultimately to unequal access to transplantation for those with end-stage liver disease. Calling out these disparities is only the first step towards implementing solutions that can improve health equity and clinical outcomes for everyone. Multi-level interventions along the care continuum for chronic liver disease are needed to mitigate these disparities and provide equitable access to care.
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Affiliation(s)
- David Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
| | - Julius Wilder
- Division of Gastroenterology, Duke University, Durham, NC, USA
| | - Norah Terrault
- Division of GI and Liver Diseases, University of Southern California, Los Angeles, CA, USA.
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Chen J, Wu Y, Hao W, You J, Wu L. Non-canonical hepatic androgen receptor mediates glucagon sensitivity in female mice through the PGC1α/ERRα/mitochondria axis. Cell Rep 2025; 44:115188. [PMID: 39792556 DOI: 10.1016/j.celrep.2024.115188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/27/2024] [Accepted: 12/19/2024] [Indexed: 01/12/2025] Open
Abstract
Glucagon has recently been found to modulate liver fat content, in addition to its role in regulating gluconeogenesis. However, the precise mechanisms by which glucagon signaling synchronizes glucose and lipid metabolism in the liver remain poorly understood. By employing chemical and genetic approaches, we demonstrate that inhibiting the androgen receptor (AR) impairs the ability of glucagon to stimulate gluconeogenesis and lipid catabolism in primary hepatocytes and female mice. Notably, AR expression in the liver of female mice is up to three times higher than that in their male littermates, accounting for the more pronounced response to glucagon in females. Mechanistically, hepatic AR promotes energy metabolism and enhances lipid breakdown for liver glucose production in response to glucagon treatment through the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/estrogen-related receptor alpha (ERRα)-mitochondria axis. Overall, our findings highlight the crucial role of hepatic AR in mediating glucagon signaling and the sexual dimorphism in hepatic glucagon sensitivity.
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Affiliation(s)
- Jie Chen
- Fudan University, Shanghai, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China
| | - Yuanyuan Wu
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Wenyuan Secondary School Affiliated to Xuejun High School, Hangzhou, Zhejiang, China
| | - Wanyu Hao
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Pharmaceuticals, Hangzhou, Zhejiang, China
| | - Jia You
- Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China.
| | - Lianfeng Wu
- Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China.
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Al Ghaithi F, Waly MI, Al-Farsi Y, Al Mukhaini Z, Al Balushi R, Almashrafi A. Biochemical and nutritional determinants of non-alcoholic fatty liver disease in Omani adult patients: a case-control study. INTERNATIONAL JOURNAL OF NUTRITION, PHARMACOLOGY, NEUROLOGICAL DISEASES 2024; 14:407-415. [DOI: 10.4103/ijnpnd.ijnpnd_57_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 08/05/2024] [Indexed: 01/03/2025]
Abstract
Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is a risk factor for atherosclerosis, diabetes, kidney disease, and liver cirrhosis. Limited research exists on the biochemical and nutritional elements influencing NAFLD among adult patients in Oman. Objective: This study aimed to characterize the biochemical parameters and nutritional factors of Omani adults diagnosed with NAFLD at the Diwan Polyclinic in Muscat, Oman. Methods: This retrospective case–control study included 104 participants (52 cases and 52 controls) who have 2 or more risk factors for NAFLD and were referred to the Radiology department from January 2021 to January 2022 for abdominal ultrasound after Internal Medicine consultations. A validated scale, incorporating a semi-quantitative food frequency questionnaire, was employed. Results: The study revealed a significantly higher risk of NAFLD among men (69%) compared to women (31%). A common characteristic among participants was a prior diabetes diagnosis, 61.5% of the case group and 65% of the control group. While average liver enzyme levels were within the normal range for both groups, alanine transaminase levels were notably elevated in the case group. The case group exhibited a significantly higher average caloric intake than the control group. Conclusion: NAFLD is significantly more common among men. Alanine transaminase is significantly high in NAFLD group, which might be considered as a biochemical marker for NAFLD, but further investigations are needed. Moreover, high daily caloric intake is directly related to NAFLD.
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Affiliation(s)
| | - Mostafa I. Waly
- Food Science and Nutrition Department, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
| | - Yahya Al-Farsi
- Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Oman
| | | | - Ruqaiya Al Balushi
- Food Science and Nutrition Department, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman
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Zheng W, Pang K, Min Y, Wu D. Prospect and Challenges of Volatile Organic Compound Breath Testing in Non-Cancer Gastrointestinal Disorders. Biomedicines 2024; 12:1815. [PMID: 39200279 PMCID: PMC11351786 DOI: 10.3390/biomedicines12081815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 07/16/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett's esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring.
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Affiliation(s)
- Weiyang Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;
| | - Ke Pang
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (K.P.); (Y.M.)
| | - Yiyang Min
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (K.P.); (Y.M.)
| | - Dong Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;
- Clinical Epidemiology Unit, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
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7
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DiStefano JK, Piras IS, Wu X, Sharma R, Garcia-Mansfield K, Willey M, Lovell B, Pirrotte P, Olson ML, Shaibi GQ. Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis. Clin Nutr ESPEN 2024; 60:333-342. [PMID: 38479932 PMCID: PMC10937812 DOI: 10.1016/j.clnesp.2024.02.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND Recent studies suggest that proteomic cargo of extracellular vesicles (EVs) may play a role in metabolic improvements following lifestyle interventions. However, the relationship between changes in liver fat and circulating EV-derived protein cargo following intervention remains unexplored. METHODS The study cohort comprised 18 Latino adolescents with obesity and hepatic steatosis (12 males/6 females; average age 13.3 ± 1.2 y) who underwent a six-month lifestyle intervention. EV size distribution and concentration were determined by light scattering intensity; EV protein composition was characterized by liquid chromatography tandem-mass spectrometry. RESULTS Average hepatic fat fraction (HFF) decreased 23% by the end of the intervention (12.5% [5.5] to 9.6% [4.9]; P = 0.0077). Mean EV size was smaller post-intervention compared to baseline (120.2 ± 16.4 nm to 128.4 ± 16.5 nm; P = 0.031), although the difference in mean EV concentration (1.1E+09 ± 4.1E+08 particles/mL to 1.1E+09 ± 1.8E+08 particles/mL; P = 0.656)) remained unchanged. A total of 462 proteins were identified by proteomic analysis of plasma-derived EVs from participants pre- and post-intervention, with 113 proteins showing differential abundance (56 higher and 57 lower) between the two timepoints (adj-p <0.05). Pathway analysis revealed enrichment in complement cascade, initial triggering of complement, creation of C4 and C2 activators, and regulation of complement cascade. Hepatocyte-specific EV affinity purification identified 40 proteins with suggestive (p < 0.05) differential abundance between pre- and post-intervention samples. CONCLUSIONS Circulating EV-derived proteins, particularly those associated with the complement cascade, may contribute to improvements in liver fat in response to lifestyle intervention.
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Affiliation(s)
- Johanna K DiStefano
- Diabetes and Metabolic Disease Research Unit, Translational Genomics Research Institute, Phoenix, AZ, USA.
| | - Ignazio S Piras
- Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Xiumei Wu
- Diabetes and Metabolic Disease Research Unit, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Ritin Sharma
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Krystine Garcia-Mansfield
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Maya Willey
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Brooke Lovell
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Patrick Pirrotte
- Integrated Mass Spectrometry Shared Resource, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Micah L Olson
- Division of Endocrinology and Diabetes, Phoenix Children's, Phoenix, AZ, USA; Center for Health Promotion and Disease Prevention, Edson College of Nursing, Arizona State University, Phoenix, AZ, USA
| | - Gabriel Q Shaibi
- Division of Endocrinology and Diabetes, Phoenix Children's, Phoenix, AZ, USA; Center for Health Promotion and Disease Prevention, Edson College of Nursing, Arizona State University, Phoenix, AZ, USA
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Elsaid MI, Bridges JFP, Mumtaz K, Li N, Sobotka L, Rustgi VK, Paskett ED. The impact of metabolic syndrome severity on racial and ethnic disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease. PLoS One 2024; 19:e0299836. [PMID: 38489287 PMCID: PMC10942082 DOI: 10.1371/journal.pone.0299836] [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: 10/17/2023] [Accepted: 02/15/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND & AIMS Previous studies have examined the effects of metabolic syndrome (MetS) rather than its severity on race and ethnic disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We used the MetS severity score, a validated sex-race-ethnicity-specific severity measure, to examine the effects of race/ethnicity on the association between MetS severity and MASLD. METHODS This study included 10,605 adult participants from the Third National Health and Nutrition Examination Survey. The MASLD diagnosis was based on ultrasound findings in patients without excessive alcohol intake or other liver diseases. MetS severity Z-scores were calculated and stratified into four categories low (1st-50th), moderate (>50th-75th), high (>75th-90th), and very high (>90th+)]. Multivariable adjusted logistic regression models with complex survey methods were used to test the effect of MetS severity on MASLD. RESULTS The age-adjusted MASLD prevalence was 17.4%, 25.7%, 42.5, and 54.9% in adults with mild, moderate, high, and very high MetS severities, respectively (P-trend <0.001). MetS severity was significantly higher in patients with MASLD than in those without [mean percentile 60th vs. 44th, P<0.001]. Among patients with MASLD, Mexican-American and Black non-Hispanic females had significantly higher age-adjusted MetS severity (68th and 61st, respectively) than White non-Hispanic females 54th, while Black non-Hispanic males had significantly lower MetS severity (56th) than White non-Hispanic males (70th) (P-Interaction = 0.02). Adults with high and very high MetS severity had 2.27 (95% CI:1.70 to 3.03) and 3.12 (95% CI:2.20 to 4.42), respectively, higher adjusted odds of MASLD than those with mild MetS severity. CONCLUSIONS Racial/ethnic disparities in MetS severity play a pivotal role in the risk of MASLD. Our findings highlight the potential clinical utility of the MetS severity score in identifying at-risk individuals, which will help guide targeted prevention and tailoring management strategies to mitigate the MASLD burden.
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Affiliation(s)
- Mohamed I. Elsaid
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
- Center for Biostatistics, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
- Department of Internal Medicine, Division of Medical Oncology, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
| | - John F. P. Bridges
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
- Department of Health, Behavior and Society, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Khalid Mumtaz
- Division of Gastroenterology, Hepatology, & Nutrition, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
| | - Na Li
- Division of Gastroenterology, Hepatology, & Nutrition, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
| | - Lindsay Sobotka
- Division of Gastroenterology, Hepatology, & Nutrition, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
| | - Vinod K. Rustgi
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
- Center for Liver Diseases and Masses, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
| | - Electra D. Paskett
- Division of Population Sciences, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States of America
- Department of Internal Medicine, Division of Cancer Prevention and Control, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America
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Cao L, An Y, Liu H, Jiang J, Liu W, Zhou Y, Shi M, Dai W, Lv Y, Zhao Y, Lu Y, Chen L, Xia Y. Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis. BMC Med 2024; 22:101. [PMID: 38448943 PMCID: PMC10919055 DOI: 10.1186/s12916-024-03315-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 02/23/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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Affiliation(s)
- Limin Cao
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Yu An
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Huiyuan Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Jinguo Jiang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wenqi Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yuhan Zhou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Mengyuan Shi
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wei Dai
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanling Lv
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuhong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanhui Lu
- School of Nursing, Peking University, 38 Xueyuan Rd, Haidian District, Beijing, 100191, China.
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China.
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China.
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Fantasia KL, Austad K, Mohanty A, Long MT, Walkey A, Drainoni ML. Safety-Net Primary Care and Endocrinology Clinicians' Knowledge and Perspectives on Screening for Nonalcoholic Fatty Liver Disease: A Mixed-Methods Evaluation. Endocr Pract 2024; 30:270-277. [PMID: 38184239 DOI: 10.1016/j.eprac.2023.12.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/22/2023] [Accepted: 12/27/2023] [Indexed: 01/08/2024]
Abstract
OBJECTIVE Clinical guidelines have expanded the indications for nonalcoholic fatty liver disease (NAFLD) screening to type 2 diabetes mellitus and obesity, which are conditions common in populations who receive care in urban safety-net settings. This study aimed to evaluate safety-net primary care and endocrinology clinicians' knowledge of NAFLD, determine barriers and facilitators to screening, and examine perspectives on the use of electronic health record tools for risk assessment. METHODS Sequential explanatory mixed methods using survey and qualitative interviews with primary care, primary care subspecialty, and endocrinology clinicians in an urban safety-net health care system. RESULTS A total of 109 participants completed the survey (36.5% response rate), and 13 participated in interviews. Most respondents underestimated or did not know the prevalence of NAFLD (68%), did not use the recommended noninvasive tests for risk stratification (65%), and few were comfortable with screening for (27%) or managing (17%) NAFLD. Endocrinologists had greater knowledge of risk factors but lower rates of comfort and more often felt that screening was not their responsibility. The qualitative themes included the following: (1) lack of knowledge about screening, (2) concern for underdiagnosing NAFLD, (3) perception of severity impacts beliefs about screening, (4) screening should occur in primary care but is not normative practice, (5) concerns exist about benefit, (6) competing demands with a complex population hinder screening, and (7) a need for easier ways to integrate screening into practice. CONCLUSION Knowledge gaps may hamper uptake of new guidelines for NAFLD screening in primary care and endocrinology clinics in an urban safety-net health care system. Implementation strategies focused on training and educating clinicians and informed by behavioral economics may increase screening.
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Affiliation(s)
- Kathryn L Fantasia
- Section of Endocrinology Diabetes and Nutrition, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts; Evans Center for Implementation and Improvement Sciences (CIIS), Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts.
| | - Kirsten Austad
- Evans Center for Implementation and Improvement Sciences (CIIS), Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts; Department of Family Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
| | - Arpan Mohanty
- Section of Gastroenterology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
| | - Michelle T Long
- Section of Gastroenterology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts; Medical & Science, Clinical Drug Development, Novo Nordisk A/S, Vandtårnsvej, Søborg, Denmark
| | - Allan Walkey
- Evans Center for Implementation and Improvement Sciences (CIIS), Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts; Section of Pulmonary, Allergy, Critical Care and Sleep, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
| | - Mari-Lynn Drainoni
- Evans Center for Implementation and Improvement Sciences (CIIS), Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts; Section of Infectious Diseases, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts; Department of Health Law Policy and Management, Boston University School of Public Health, Boston, Massachusetts
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11
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Moura PC, Raposo M, Vassilenko V. Breath biomarkers in Non-Carcinogenic diseases. Clin Chim Acta 2024; 552:117692. [PMID: 38065379 DOI: 10.1016/j.cca.2023.117692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/02/2023] [Accepted: 12/03/2023] [Indexed: 12/19/2023]
Abstract
The analysis of volatile organic compounds (VOCs) from human matrices like breath, perspiration, and urine has received increasing attention from academic and medical researchers worldwide. These biological-borne VOCs molecules have characteristics that can be directly related to physiologic and pathophysiologic metabolic processes. In this work, gathers a total of 292 analytes that have been identified as potential biomarkers for the diagnosis of various non-carcinogenic diseases. Herein we review the advances in VOCs with a focus on breath biomarkers and their potential role as minimally invasive tools to improve diagnosis prognosis and therapeutic monitoring.
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Affiliation(s)
- Pedro Catalão Moura
- Laboratory for Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, NOVA University of Lisbon, Campus FCT-UNL, 2829-516, Caparica, Portugal.
| | - Maria Raposo
- Laboratory for Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, NOVA University of Lisbon, Campus FCT-UNL, 2829-516, Caparica, Portugal.
| | - Valentina Vassilenko
- Laboratory for Instrumentation, Biomedical Engineering and Radiation Physics (LIBPhys-UNL), Department of Physics, NOVA School of Science and Technology, NOVA University of Lisbon, Campus FCT-UNL, 2829-516, Caparica, Portugal.
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12
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Tiniakos DG, Anstee QM, Brunt EM, Burt AD. Fatty Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:330-401. [DOI: 10.1016/b978-0-7020-8228-3.00005-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Pourteymour S, Drevon CA, Dalen KT, Norheim FA. Mechanisms Behind NAFLD: a System Genetics Perspective. Curr Atheroscler Rep 2023; 25:869-878. [PMID: 37812367 DOI: 10.1007/s11883-023-01158-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2023] [Indexed: 10/10/2023]
Abstract
PURPOSE OF REVIEW To summarize the key factors contributing to the onset and progress of nonalcoholic fatty liver disease (NAFLD) and put them in a system genetics context. We particularly focus on how genetic regulation of hepatic lipids contributes to NAFLD. RECENT FINDINGS NAFLD is characterized by excessive accumulation of fat in the liver. This can progress to steatohepatitis (inflammation and hepatocyte injury) and eventually, cirrhosis. The severity of NAFLD is determined by a combination of factors including obesity, insulin resistance, and lipotoxic lipids, along with genetic susceptibility. Numerous studies have been conducted on large human cohorts and mouse panels, to identify key determinants in the genome, transcriptome, proteome, lipidome, microbiome and different environmental conditions contributing to NAFLD. We review common factors contributing to NAFLD and put them in a systems genetics context. In particular, we describe how genetic regulation of liver lipids contributes to NAFLD. The combination of an unhealthy lifestyle and genetic predisposition increases the likelihood of accumulating lipotoxic specie lipids that may be one of the driving forces behind developing severe forms of NAFLD.
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Affiliation(s)
- Shirin Pourteymour
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Blindern, PO Box 1046, 0317, Oslo, Norway
| | - Christian A Drevon
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Blindern, PO Box 1046, 0317, Oslo, Norway
- Vitas Ltd. Oslo Science Park, Oslo, Norway
| | - Knut Tomas Dalen
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Blindern, PO Box 1046, 0317, Oslo, Norway
| | - Frode A Norheim
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Blindern, PO Box 1046, 0317, Oslo, Norway.
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14
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Reinshagen M, Kabisch S, Pfeiffer AF, Spranger J. Liver Fat Scores for Noninvasive Diagnosis and Monitoring of Nonalcoholic Fatty Liver Disease in Epidemiological and Clinical Studies. J Clin Transl Hepatol 2023; 11:1212-1227. [PMID: 37577225 PMCID: PMC10412706 DOI: 10.14218/jcth.2022.00019] [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: 09/15/2022] [Revised: 12/16/2022] [Accepted: 03/21/2023] [Indexed: 07/03/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome and type 2 diabetes and independently contributes to long-term complications. Being often asymptomatic but reversible, it would require population-wide screening, but direct diagnostics are either too invasive (liver biopsy), costly (MRI) or depending on the examiner's expertise (ultrasonography). Hepatosteatosis is usually accommodated by features of the metabolic syndrome (e.g. obesity, disturbances in triglyceride and glucose metabolism), and signs of hepatocellular damage, all of which are reflected by biomarkers, which poorly predict NAFLD as single item, but provide a cheap diagnostic alternative when integrated into composite liver fat indices. Fatty liver index, NAFLD LFS, and hepatic steatosis index are common and accurate indices for NAFLD prediction, but show limited accuracy for liver fat quantification. Other indices are rarely used. Hepatic fibrosis scores are commonly used in clinical practice, but their mandatory reflection of fibrotic reorganization, hepatic injury or systemic sequelae reduces sensitivity for the diagnosis of simple steatosis. Diet-induced liver fat changes are poorly reflected by liver fat indices, depending on the intervention and its specific impact of weight loss on NAFLD. This limited validity in longitudinal settings stimulates research for new equations. Adipokines, hepatokines, markers of cellular integrity, genetic variants but also simple and inexpensive routine parameters might be potential components. Currently, liver fat indices lack precision for NAFLD prediction or monitoring in individual patients, but in large cohorts they may substitute nonexistent imaging data and serve as a compound biomarker of metabolic syndrome and its cardiometabolic sequelae.
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Affiliation(s)
- Mona Reinshagen
- Department of Endocrinology and Metabolism, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
- Deutsches Zentrum für Diabetesforschung e.V., Geschäftsstelle am Helmholtz-Zentrum München, Neuherberg, Germany
| | - Stefan Kabisch
- Department of Endocrinology and Metabolism, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
- Deutsches Zentrum für Diabetesforschung e.V., Geschäftsstelle am Helmholtz-Zentrum München, Neuherberg, Germany
| | - Andreas F.H. Pfeiffer
- Department of Endocrinology and Metabolism, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
- Deutsches Zentrum für Diabetesforschung e.V., Geschäftsstelle am Helmholtz-Zentrum München, Neuherberg, Germany
| | - Joachim Spranger
- Department of Endocrinology and Metabolism, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
- Deutsches Zentrum für Diabetesforschung e.V., Geschäftsstelle am Helmholtz-Zentrum München, Neuherberg, Germany
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15
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Reinson T, Buchanan RM, Byrne CD. Identification of individuals at risk of hepatocellular carcinoma: screening for clinically significant liver fibrosis in patients with T2DM. Expert Rev Endocrinol Metab 2023; 18:355-359. [PMID: 37587863 DOI: 10.1080/17446651.2023.2248242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/17/2023] [Accepted: 08/10/2023] [Indexed: 08/18/2023]
Affiliation(s)
- Tina Reinson
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | - Ryan M Buchanan
- National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
- Primary Care and Population Science, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- National Institute for Health and Care Research, Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
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16
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Teng PC, Huang DQ, Lin TY, Noureddin M, Yang JD. Diabetes and Risk of Hepatocellular Carcinoma in Cirrhosis Patients with Nonalcoholic Fatty Liver Disease. Gut Liver 2023; 17:24-33. [PMID: 36530125 PMCID: PMC9840929 DOI: 10.5009/gnl220357] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/09/2022] [Accepted: 09/19/2022] [Indexed: 12/23/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. NAFLD is a hepatic manifestation of insulin resistance, the core pathophysiology of diabetes. Multiple clinical studies show that diabetes increases the risk of liver disease progression and cirrhosis development in patients with NAFLD. Diabetes has causal associations with many different cancers, including hepatocellular carcinoma (HCC). More recent studies demonstrate that diabetes increases the risk of HCC in patients with underlying NAFLD cirrhosis, confirming the direct hepatocarcinogenic effect of diabetes among cirrhosis patients. Diabetes promotes hepatocarcinogenesis via the activation of inflammatory cascades producing reactive oxygen species and proinflammatory cytokines, leading to genomic instability, cellular proliferation, and inhibition of apoptosis. Given the global increase in the burden of NAFLD and HCC, high-risk patients such as older diabetic individuals should be carefully monitored for HCC development. Future larger studies should explore whether the effect of diabetes on HCC risk in NAFLD cirrhosis is modifiable by the type of antidiabetic medication and the effectiveness of diabetes control.
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Affiliation(s)
- Pai-Chi Teng
- Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei, Taiwan
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Daniel Q. Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Ting-Yi Lin
- Doctoral Degree Program of Translational Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan
| | - Mazen Noureddin
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Ju Dong Yang
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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17
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Abdel-Hamid MS, Mansour AM, Hassan MH, Abdelhady R, Elsadek BEM, El-Sayed ESM, Salama SA. Estrogen Attenuates Diethylnitrosamine-Induced Hepatocellular Carcinoma in Female Rats via Modulation of Estrogen Receptor/FASN/CD36/IL-6 Axis. Biol Pharm Bull 2023; 46:1558-1568. [PMID: 37914358 DOI: 10.1248/bpb.b23-00342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
Abstract
This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.
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Affiliation(s)
| | - Ahmed M Mansour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University
| | - Memy H Hassan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University
| | - Rasha Abdelhady
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Fayoum University
| | - Bakheet E M Elsadek
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University
| | - El-Sayed M El-Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University
| | - Salama A Salama
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University
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18
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Shah PA, Patil R, Harrison SA. NAFLD-related hepatocellular carcinoma: The growing challenge. Hepatology 2023; 77:323-338. [PMID: 35478412 PMCID: PMC9970023 DOI: 10.1002/hep.32542] [Citation(s) in RCA: 123] [Impact Index Per Article: 61.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/15/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity worldwide. With the obesity pandemic, NAFLD-related HCC is contributing to the burden of disease exponentially. Genetic predisposition and clinical risk factors for NAFLD-related HCC have been identified. Cirrhosis is a well-known and major risk factor for NAFLD-related HCC. However, the occurrence of NAFLD-related HCC in patients without cirrhosis is increasingly recognized and poses a significant challenge regarding cancer surveillance. It is of paramount importance to develop optimal risk stratification scores and models to identify subsets of the population at high risk so they can be enrolled in surveillance programs. In this review, we will discuss the risks and prediction models for NAFLD-related HCC.
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Affiliation(s)
- Pir Ahmad Shah
- Department of Internal Medicine, University of Texas Health Science Center, San Antonio, Texas, USA
| | - Rashmee Patil
- South Texas Research Institute, Edinburg, Texas, USA
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19
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Prieto Ortíz JE, Sánchez Luque CB, Ortega Quiróz RJ. Hígado graso (parte 1): aspectos generales, epidemiología, fisiopatología e historia natural. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2022; 37:420-433. [DOI: 10.22516/25007440.952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
El hígado graso no alcohólico (NAFLD) se define por la presencia de grasa o esteatosis en los hepatocitos y abarca un espectro que va desde la esteatosis simple, pasa por la esteatohepatitis no alcohólica (NASH) con inflamación y fibrosis, y finaliza en la cirrosis. Se considera una prevalencia mundial global cercana al 25% en la población general y se diagnóstica entre los 40 y 50 años, con variaciones respecto al sexo predominante y con diferencias étnicas (la población hispana es la más afectada). El hígado graso está asociado al síndrome metabólico (SM), y la obesidad se considera el principal factor de riesgo con su presencia y con su progresión.
El hígado graso es un trastorno complejo y muy heterogéneo en su fisiopatología, que resulta de la interacción de múltiples elementos: factores genéticos, epigenéticos, ambientales, culturales, entre otros. Todo ello en conjunto lleva a incremento paulatino de grasa hepática, resistencia a la insulina y alteraciones hormonales y de la microbiota intestinal, lo que genera un daño hepatocelular a través de la formación de radicales libres de oxígeno y activación de la fibrogénesis hepática.
La historia natural del hígado graso es dinámica: los pacientes con esteatosis simple tienen bajo riesgo de progresión a cirrosis, mientras que en los pacientes con NASH este riesgo se aumenta; sin embargo, el proceso puede ser reversible y algunas personas tendrán una mejoría espontánea. La fibrosis parece ser el determinante de la mortalidad global y de los desenlaces asociados a la enfermedad hepática; se considera que en todos los pacientes la fibrosis empeora una etapa cada 14 años y en NASH empeora en una etapa cada 7 años. Estudios previos concluyen que aproximadamente 20% de los casos de esteatosis simple progresan a NASH y que, de ellos, aproximadamente el 20% progresan a cirrosis, con presencia de hepatocarcinoma (HCC) en el 5% a 10% de ellos.
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20
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Cardoso AC, Tovo CV, Leite NC, El Bacha IA, Calçado FL, Coral GP, Sammarco GN, Cravo C, Carvalho Filho RJ, de Mello Perez R, Luiz RR, Parise ER, Villela-Nogueira CA. Validation and Performance of FibroScan®-AST (FAST) Score on a Brazilian Population with Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2022; 67:5272-5279. [PMID: 35091842 DOI: 10.1007/s10620-021-07363-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 12/07/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIM FAST score has a good performance for diagnosing the composite of NASH + NAS ≥ 4 + F ≥ 2. However, it has not been evaluated in Latin American individuals with nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the performance of the FAST score in a Brazilian NAFLD population. METHODS Cross-sectional study was held in ≥ 18 years NAFLD patients diagnosed by ultrasonography and submitted to liver biopsy (LB). Liver stiffness (LSM) and CAP measurements were performed with FibroScan®, using M (BMI < 32 kg/m2) or XL probes. Area under receiver operating characteristic (AUROC) curves were calculated as well as sensitivity (S), specificity (Spe), positive predictive value (VPP) and negative predictive value (NPV) for the previously established FAST score cut-offs. RESULTS Among 287 patients included (75% female; mean age 55 ± 10 years), NASH + NAS ≥ 4 + F ≥ 2 was reported in 30% of LB. For the FAST cut-off of 0.35, the S and NPV to rule out NASH + NAS ≥ 4 + F ≥ 2 were 78.8% and 87.8%, respectively. Regarding the cut-off of 0.67, the Spe and PPV to rule-in NASH + NAS ≥ 4 + F ≥ 2 were 89.1%, 61.8%, respectively. The AUROC of FAST for all included patients was 0.78 (95% CI 0.72-0.84) and for those with ≥ 32 kg/m2 was 0.81 (95% CI 0.74-0.88). CONCLUSION FAST score has a good performance in a Brazilian NAFLD population, even in patients with higher BMI when the XL probe is adopted. Therefore, FAST can be used as a noninvasive screening tool mainly for excluding the diagnosis of progressive NASH, reducing the number of unnecessary liver biopsies.
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Affiliation(s)
- Ana Carolina Cardoso
- Hepatology Unit - Clementino Fraga Filho University Hospital - School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 - Room 9E16, Rio de Janeiro, 29913-941, Brazil
| | - Cristiane Valle Tovo
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
| | - Nathalie Carvalho Leite
- Hepatology Unit - Clementino Fraga Filho University Hospital - School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 - Room 9E16, Rio de Janeiro, 29913-941, Brazil
| | - Ibrahim A El Bacha
- Division of Gastroenterology, Hepatology Section, Federal University of São Paulo, São Paulo, Brazil
| | - Fernanda Luiza Calçado
- Hepatology Unit - Clementino Fraga Filho University Hospital - School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 - Room 9E16, Rio de Janeiro, 29913-941, Brazil
| | - Gabriela Perdomo Coral
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil
| | - Glauco Navas Sammarco
- Division of Gastroenterology, Hepatology Section, Federal University of São Paulo, São Paulo, Brazil
| | - Claudia Cravo
- Hepatology Unit - Clementino Fraga Filho University Hospital - School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 - Room 9E16, Rio de Janeiro, 29913-941, Brazil
| | | | - Renata de Mello Perez
- Hepatology Unit - Clementino Fraga Filho University Hospital - School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 - Room 9E16, Rio de Janeiro, 29913-941, Brazil
| | - Ronir Raggio Luiz
- Institute of Public Health Studies, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Edison Roberto Parise
- Division of Gastroenterology, Hepatology Section, Federal University of São Paulo, São Paulo, Brazil
| | - Cristiane A Villela-Nogueira
- Hepatology Unit - Clementino Fraga Filho University Hospital - School of Medicine, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 - Room 9E16, Rio de Janeiro, 29913-941, Brazil.
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21
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Monitoring and treatment of Wilson disease: progress and challenges. Lancet Gastroenterol Hepatol 2022; 7:1063-1065. [DOI: 10.1016/s2468-1253(22)00284-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 08/19/2022] [Accepted: 08/20/2022] [Indexed: 11/19/2022]
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22
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Singh SP, Panigrahi MK, Patel A, Viswanathan L, Rath MM, Kar SK, Harrison SA. Comparison of Clinical, Biochemical, and Histopathologic Profiles between NAFLD in Asian-Indians and United States Adults. Euroasian J Hepatogastroenterol 2022; 12:S15-S18. [PMID: 36466104 PMCID: PMC9681572 DOI: 10.5005/jp-journals-10018-1362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
Abstract
BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is very common in both Asian and Western countries. Geographic variation leads to differences in epidemiological and demographic characters of NAFLD patients. Studies conducted upon different ethnic groups in the United States (US) show a higher prevalence of NAFLD in Hispanics and African-Americans. There is however, a paucity of studies involving Asians. It has been observed that Asian-Indian NAFLD patients have unique characteristics compared to their counterparts in the West. This study is the first attempt at comparing the characteristics of Asian-Indian and US NAFLD patients. MATERIALS AND METHODS A retrospective analysis of clinical, biochemical, and histological data was performed for 633 Asian-Indian NAFLD patients and 451 US NAFLD patients. Clinical parameters [age, gender, body mass index (BMI), diabetes, hypertension, etc.], biochemical tests (liver function tests, lipid profile, and fasting blood sugar), hepatic ultrasound and hepatic histology were compared between the two cohorts. RESULTS Eighty-two percent of US NAFLD patients were more than 40 years of age compared to 51.3% of Asian-Indian patients (p <0.01). US (male 56.3%) and Asian-Indian (male 81.7%) (p <0.01) patients differed from each other as regards gender prevalence. Rates of obesity were greater in the US patients compared to Asian-Indians (BMI 32.6 ± 5.3 kg/m2 vs 26.2 ± 3.4 kg/m2). There was a higher prevalence of both diabetes and hypertension (diabetes 42.1% vs 33%, and hypertension 56.8% vs 29.7%, p ≤0.01) in US patients. ALT levels were also significantly higher in US NAFLD patients compared to Asian-Indians (ALT 82.78 ± 71.30 vs 53.66 ± 37, p ≤0.01). A higher proportion of US patients were found to have the more advanced liver disease at the time of diagnosis compared to Asian-Indians (Stage 3 fibrosis 10.42% vs 0%, and Stage 4 fibrosis 2.66% vs 0%, p <0.01). CONCLUSION Asian-Indian and US NAFLD patients differ significantly on several parameters. Further studies need to be carried out to understand the mechanistic basis of these differences better. HOW TO CITE THIS ARTICLE Singh SP, Panigrahi MK, Patel A, et al. Comparison of Clinical, Biochemical, and Histopathologic Profiles between NAFLD in Asian-Indians and United States Adults. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S15-S18.
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Affiliation(s)
- Shivaram P Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Odisha, India
| | | | - Anish Patel
- Department of Gastroenterology and Hepatology, Brooke Army Medical Center, San Antonio, Texas, United States of America
| | - Lavanya Viswanathan
- Department of Gastroenterology and Hepatology, David Grant Medical Center, Fairfield, California, United States of America
| | - Mitali M Rath
- Department of Pathology, Hi-Tech Medical College and Hospital, Bhubaneswar, Odisha, India
| | - Sanjib K Kar
- Department of Gastroenterology, Gastro Liver Care, Cuttack, Odisha, India
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Zhou K, Dodge JL, Yuan L, Terrault NA. Metabolic Risk Profiles for Hepatic Steatosis Differ by Race/Ethnicity: An Elastography-Based Study of US Adults. Dig Dis Sci 2022; 67:3340-3355. [PMID: 34173916 DOI: 10.1007/s10620-021-07124-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/16/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Most population-based studies of risk profiles for liver steatosis have relied upon serum markers (e.g., ALT or FIB-4) or ultrasound steatosis index to define cases. We sought to examine racial/ethnic differences in metabolic risk factors associated with liver steatosis and fibrosis at the population level using elastography-based measures. METHODS In total, 4509 adults completed vibration-controlled transient elastography (VCTE) with controlled attenuated parameter (CAP) examinations in the 2017-2018 National Health and Nutrition Examinations Survey. Race/ethnicity was self-identified; metabolic parameters included waist circumference, obesity, diabetes, hypertension, and hyperlipidemia. Primary outcome was steatosis defined by CAP score ≥ 280 decibels per meter and secondary outcome significant fibrosis by VCTE median stiffness ≥ 8 kilopascals. Race-specific logistic regression models were performed to assess the relationship between metabolic parameters and hepatic steatosis and fibrosis. RESULTS Prevalence of elastography-based hepatic steatosis was > 30% for all race/ethnicities. Steatosis was associated with increasing waist circumference for all race/ethnicities (OR ranging 1.7-2.3, p < 0.01). Steatosis was associated with diabetes for Whites (OR 2.4, 95% CI 1.2-4.7), Asians (OR 3.0, 1.4-6.3), and Hispanics (OR 2.2, 1.3-3.6), but not Blacks (OR 1.3, 0.8-2.2); hypertension for Whites (OR 1.7, 1.3-4.7) and Asians (OR 2.1, 1.1-3.8); and hyperlipidemia for Blacks only (OR 2.2, 1.3-3.7). Of metabolic risk factors, higher odds of fibrosis were demonstrated with higher waist circumference per 10 cm increase (OR 2.1, 1.8-2.4) and diabetes (OR 2.5, 1.6-3.7), but the effect of diabetes was present in all racial/ethnic groups except Blacks (p-interaction < 0.05). CONCLUSION Blacks have a distinct metabolic phenotype for steatosis, while Asians, Whites, and Hispanics are more similar. Racial/ethnic differences in risk profiles are important to consider in prevention, screening strategies, and interventions for fatty liver disease.
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Affiliation(s)
- Kali Zhou
- Division of Gastrointestinal and Liver Diseases, University of Southern California, 1450 San Pablo St. HC4, Room 3000, Los Angeles, CA, 90033, USA.
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
| | - Jennifer L Dodge
- Division of Gastrointestinal and Liver Diseases, University of Southern California, 1450 San Pablo St. HC4, Room 3000, Los Angeles, CA, 90033, USA
- Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Liyun Yuan
- Division of Gastrointestinal and Liver Diseases, University of Southern California, 1450 San Pablo St. HC4, Room 3000, Los Angeles, CA, 90033, USA
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, 1450 San Pablo St. HC4, Room 3000, Los Angeles, CA, 90033, USA
- Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Noureddin M, Ntanios F, Malhotra D, Hoover K, Emir B, McLeod E, Alkhouri N. Predicting NAFLD prevalence in the United States using National Health and Nutrition Examination Survey 2017-2018 transient elastography data and application of machine learning. Hepatol Commun 2022; 6:1537-1548. [PMID: 35365931 PMCID: PMC9234676 DOI: 10.1002/hep4.1935] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 02/10/2022] [Accepted: 02/19/2022] [Indexed: 12/12/2022] Open
Abstract
This cohort analysis investigated the prevalence of nonalcoholic fatty liver disease (NAFLD) and NAFLD with fibrosis at different stages, associated clinical characteristics, and comorbidities in the general United States population and a subpopulation with type 2 diabetes mellitus (T2DM), using the National Health and Nutrition Examination Survey (NHANES) database (2017-2018). Machine learning was explored to predict NAFLD identified by transient elastography (FibroScan® ). Adults ≥20 years of age with valid transient elastography measurements were included; those with high alcohol consumption, viral hepatitis, or human immunodeficiency virus were excluded. Controlled attenuation parameter ≥302 dB/m using Youden's index defined NAFLD; vibration-controlled transient elastography liver stiffness cutoffs were ≤8.2, ≤9.7, ≤13.6, and >13.6 kPa for F0-F1, F2, F3, and F4, respectively. Predictive modeling, using six different machine-learning approaches with demographic and clinical data from NHANES, was applied. Age-adjusted prevalence of NAFLD and of NAFLD with F0-F1 and F2-F4 fibrosis was 25.3%, 18.9%, and 4.4%, respectively, in the overall population and 54.6%, 32.6%, and 18.3% in those with T2DM. The highest prevalence was among Mexican American participants. Test performance for all six machine-learning models was similar (area under the receiver operating characteristic curve, 0.79-0.84). Machine learning using logistic regression identified male sex, hemoglobin A1c, age, and body mass index among significant predictors of NAFLD (P ≤ 0.01). Conclusion: Data show a high prevalence of NAFLD with significant fibrosis (≥F2) in the general United States population, with greater prevalence in participants with T2DM. Using readily available, standard demographic and clinical data, machine-learning models could identify subjects with NAFLD across large data sets.
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Affiliation(s)
- Mazen Noureddin
- Karsh Division of Gastroenterology and HepatologyComprehensive Transplant CenterCedars-Sinai Medical CenterLos AngelesCaliforniaUSA
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Liu Y, Liu S, Huang J, Zhu Y, Lin S. Validation of five hepatic steatosis algorithms in metabolic-associated fatty liver disease: A population based study. J Gastroenterol Hepatol 2022; 37:938-945. [PMID: 35174539 DOI: 10.1111/jgh.15799] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/11/2021] [Accepted: 01/23/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Non-invasive hepatic steatosis algorithms are recommended in detecting metabolic-associated fatty liver disease (MAFLD) in epidemiological studies. However, the diagnostic accuracy of these models is unclear. This study aimed to evaluate the diagnostic efficiency of five common models in a national survey population. METHODS The Third National Health and Nutrition Examination Survey (NHANES III) datasets were used in this study. The fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic liver disease-liver fat score (NAFLD-LFS), the steato text (ST), and visceral adiposity index (VAI) were evaluated. RESULTS The prevalence of MAFLD in the general population was 31.2%. The proportion of MAFLD estimated using the NAFLD-LFS (30.8%) was the closest to the real number, whereas the ST model (66.1%) significantly overestimated the prevalence of MAFLD in this cohort. The FLI (36.9%) and HSI models (38.5%) also slightly overestimated the prevalence of MAFLD in the study population. The FLI had the highest area under the receiver operating characteristic (AUROC) value (0.793) among all models, with a sensitivity of 57.0%, a specificity of 83.8%, a positive predictive value (PPV) of 67.3%, and a negative predictive value (NPV) of 77.0%. The combination of the original algorithm with additional metabolic dysfunction criteria did not improve the diagnostic efficiency. The discriminative ability for MAFLD in all models was lower in participants with a normal body mass index (BMI). CONCLUSIONS Non-invasive models, especially the FLI, have satisfactory diagnostic performance in detecting MAFLD. However, models in people with normal BMIs require further development.
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Affiliation(s)
- Yuxiu Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Shiying Liu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, The First Hospital of Nanping City, Nanping, China
| | - Jiaofeng Huang
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Clinical Research Center for Liver and Intestinal Diseases of Fujian Province, Fuzhou, Fujian, China
| | - Yueyong Zhu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Clinical Research Center for Liver and Intestinal Diseases of Fujian Province, Fuzhou, Fujian, China
| | - Su Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Clinical Research Center for Liver and Intestinal Diseases of Fujian Province, Fuzhou, Fujian, China
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26
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Akter S. Non-alcoholic Fatty Liver Disease and Steatohepatitis: Risk Factors and Pathophysiology. Middle East J Dig Dis 2022; 14:167-181. [PMID: 36619154 PMCID: PMC9489315 DOI: 10.34172/mejdd.2022.270] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 01/20/2022] [Indexed: 01/11/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its progressive subtype non-alcoholic steatohepatitis (NASH) are the most prevalent liver diseases, often leading to hepatocellular carcinoma (HCC). This review aims to describe the present knowledge of the risk factors responsible for the development of NAFLD and NASH. I performed a literature review identifying studies focusing on the complex pathogenic pathway and risk factors of NAFLD and steatohepatitis. The relationship between NAFLD and metabolic syndrome is well established and widely recognized. Obesity, dyslipidemia, type 2 diabetes, hypertension, and insulin resistance are the most common risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly suggests obesity and type 2 diabetes as risk factors of NASH and HCC. However, other elements, namely gender divergences, ethnicity, genetic factors, participation of innate immune system, oxidative stress, apoptotic pathways, and adipocytokines, take a leading role in the onset and promotion of NAFLD. Pathophysiological mechanisms that are responsible for NAFLD development and subsequent progression to NASH are insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell (HSC) activation, cytokine/adipokine signaling pathways, and genetic and environmental factors. Major pathophysiological findings of NAFLD are dysfunction of adipose tissue through the enhanced flow of free fatty acids (FFAs) and release of adipokines, and altered gut microbiome that generate proinflammatory signals and cause NASH progression. Understanding the pathophysiology and risk factors of NAFLD and NASH; this review could provide insight into the development of therapeutic strategies and useful diagnostic tools.
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Affiliation(s)
- Sharmin Akter
- Department of Physiology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh,Corresponding Author: Sharmin Akter, PhD Department of Physiology, Bangladesh Agricultural University, Mymensingh-2202, Bangladesh Tel: +0088-091-67401-6 (ext. 6320) Fax: + 880 91 61510
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Allencherril RP, Markides KS, Al Snih S. Liver Disease Among Mexican Americans Aged 67 Years and Older. J Prim Care Community Health 2022; 13:21501319221116231. [PMID: 35929017 PMCID: PMC9358553 DOI: 10.1177/21501319221116231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background: The Center for Disease Control and Prevention (CDC) reports that liver disease is a significant cause of morbidity and mortality in the US, afflicting 4.5 million people in 2018, or approximately 1.7% of the American adult population. Objective: To determine the prevalence and risk factors associated with liver disease among older Mexican Americans over 18 years of follow-up. Methods: Non-institutionalized Mexican Americans aged ≥67 years (N = 1938) from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1995/96-2012/13) were studied. Measures included socio-demographic variables, self-reported liver disease, language of interview, medical conditions, hand-grip strength, physical and cognitive function, depressive symptoms, and body mass index. Generalized estimating equation models were used to estimate the odds ratio and 95% confidence interval (CI) of liver disease over time. Results: The mean age at baseline was 74.9 ± 6.0 years and 58.4% were female. The prevalence of liver disease ranged from 2.4% to 8.4%. Over time, the odds ratio of reporting liver disease was 1.17 (CI = 1.12-1.22). Older age, Spanish interview, arthritis, diabetes, heart failure, cancer, and high scores on the Mini-Mental-State-Examination were factors associated with greater odds of reporting liver disease over time. Married participants reported lower odds of liver disease over time. Conclusions: The prevalence of liver disease in this population was high, ranging from 2.4% to 8.4%. Diabetes, heart failure, arthritis, and cancer were risk factors for liver disease. Screening for liver function among patients with these morbidities may help prevent liver disease in this population with high rates of diabetes and obesity.
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Affiliation(s)
| | | | - Soham Al Snih
- The University of Texas Medical Branch, Galveston, TX, USA
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28
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Villavicencio EA, Crocker RM, Garcia DO. A Qualitative Analysis of Mexican-Origin Men's Knowledge and Cultural Attitudes Toward Non-Alcoholic Fatty Liver Disease and Interest in Risk Reduction. Am J Mens Health 2021; 15:15579883211063335. [PMID: 34872379 PMCID: PMC8655456 DOI: 10.1177/15579883211063335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Mexican-origin men are at increased risk of developing non-alcoholic fatty liver disease (NAFLD). The purpose of this qualitative research was to assess Mexican-origin men’s knowledge and cultural attitudes toward NAFLD and their interest in risk reduction. Semi-structured interviews were conducted with 11 Spanish-speaking Mexican-origin men who were considered high-risk of having NAFLD according to transient elastography (FibroScan®) continuous attenuation parameter (CAP) scores (≥280). Audio recordings of these interviews were transcribed and interpreted in their respective language to facilitate data analysis using NVivo 12. A thematic codebook was developed, from which the research team identified emerging themes. Findings demonstrated limited knowledge about NAFLD and in general chronic liver disease among Mexican-origin men. Cultural attitudes appeared to both enhance and mitigate their perceived risk for NAFLD. Interviews also revealed high interest levels for reducing NAFLD risk, with family and loved ones acting as the main motivators for engagement in healthier behaviors. Inclination toward family-based interventions was reported as a subject of interest for this high-risk population. This qualitative study suggests that the development of a NAFLD-specific intervention approach for Mexican-origin men may be feasible and should consider a familial and cultural context centered in improving lifestyle health behaviors.
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Affiliation(s)
- Edgar A Villavicencio
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, The University of Arizona, Tucson, AZ, USA
| | - Rebecca M Crocker
- Center for Border Health Disparities, Health Sciences, The University of Arizona, Tucson, AZ, USA
| | - David O Garcia
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, The University of Arizona, Tucson, AZ, USA
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Arya A, Azarmehr N, Mansourian M, Doustimotlagh AH. Inactivation of the superoxide dismutase by malondialdehyde in the nonalcoholic fatty liver disease: a combined molecular docking approach to clinical studies. Arch Physiol Biochem 2021; 127:557-564. [PMID: 31475569 DOI: 10.1080/13813455.2019.1659827] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The objective of the present study was to investigate the plasma levels of oxidative stress markers and the activity of antioxidant enzymes in NAFLD and healthy subjects. Furthermore, the interaction behaviors of malondialdehyde (MDA) with Cu/Zn superoxide dismutase (SOD1) enzyme were elucidated by molecular docking. The study involved 60 patients with NAFLD and 25 healthy volunteers. The plasma levels of oxidative stress parameters and antioxidant enzymes activity were determined. NAFLD patients had significantly higher alanine aminotransferase, MDA and nitric oxide metabolites values, as well as significantly lower total thiol and SOD activity than the control group. Based on the molecular docking, MDA could deactivate the enzymatic activity of SOD1. Impaired antioxidant defense systems may be involved in the progression of NAFLD. This study provides direct evidence at a molecular level to explain that MDA may exert its oxidant activity by specific action within the specific molecular pathway.HighlightsImpairing antioxidant defense systems may be a main factor in the progression of nonalcoholic fatty liver disease (NAFLD).Increasing MDA and NO metabolites, as well as decreasing TSH values and SOD activity in NAFLD patients as compared to control subjectsIncreasing MDA level in NAFLD patients may be inactivate SOD activity by reaction with the key residues Cu ion inside active site of the enzyme catalytic site.
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Affiliation(s)
- Arash Arya
- Internal Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Nahid Azarmehr
- Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Mahboubeh Mansourian
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Amir Hossein Doustimotlagh
- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
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Talens M, Tumas N, Lazarus JV, Benach J, Pericàs JM. What Do We Know about Inequalities in NAFLD Distribution and Outcomes? A Scoping Review. J Clin Med 2021; 10:5019. [PMID: 34768539 PMCID: PMC8584385 DOI: 10.3390/jcm10215019] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/17/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
With prevalence high and rising given the close relationship with obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is progressively becoming the most common chronic liver condition worldwide. However, little is known about the health inequalities in NAFLD distribution and outcomes. This review aims to analyze health inequalities in NAFLD distribution globally and to assess the health disparities in NAFLD-related outcomes. We conducted a scoping review of global health inequalities in NAFLD distribution and outcomes according to gender/sex, ethnicity/race, and socioeconomic position from PubMed's inception to May 2021. Ultimately, 20 articles were included in the review, most (75%) of them carried out in the United States. Males were found to have a higher NAFLD prevalence (three articles), while available evidence suggests that women have an overall higher burden of advanced liver disease and complications (four articles), whereas they are less likely to be liver-transplanted once cirrhosis develops (one article). In the US, the Hispanic population had the highest NAFLD prevalence and poorer outcomes (seven articles), whereas Whites had fewer complications than other ethnicities (two articles). Patients with low socioeconomic status had higher NAFLD prevalence (four articles) and a higher likelihood of progression and complications (five articles). In conclusion, globally there is a lack of studies analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review were based on the US population. Available evidence suggests that NAFLD distribution and outcomes show large inequalities by social group. Further research on this issue is warranted.
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Affiliation(s)
- Mar Talens
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
| | - Natalia Tumas
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
- Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain
- Centro de Investigaciones y Estudios sobre Cultura y Sociedad, Consejo Nacional de Investigaciones Científicas y Técnicas y Universidad Nacional de Córdoba, Córdoba 5016, Argentina
| | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain;
| | - Joan Benach
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
- Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain
- Transdisciplinary Research Group on Socioecological Transitions (GinTrans2), Universidad Autónoma de Madrid, 28049 Madrid, Spain
| | - Juan M. Pericàs
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
- Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain
- Liver Unit, Internal Medicine Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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Flores YN, Amoon AT, Su B, Velazquez-Cruz R, Ramírez-Palacios P, Salmerón J, Rivera-Paredez B, Sinsheimer JS, Lusis AJ, Huertas-Vazquez A, Saab S, Glenn BA, May FP, Williams KJ, Bastani R, Bensinger SJ. Serum lipids are associated with nonalcoholic fatty liver disease: a pilot case-control study in Mexico. Lipids Health Dis 2021; 20:136. [PMID: 34629052 PMCID: PMC8504048 DOI: 10.1186/s12944-021-01526-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico. Methods A nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (< 40 U/L) results in a 6-month period, and a normal liver ultrasound elastography result in January 2018. Samples were analyzed on the Sciex Lipidyzer Platform and quantified with normalization to serum volume. As many as 1100 lipid species can be identified using the Lipidyzer targeted multiple-reaction monitoring list. The association between serum lipids and NAFLD was investigated using analysis of covariance, random forest analysis, and by generating receiver operator characteristic (ROC) curves. Results NAFLD cases had differences in total amounts of serum cholesterol esters, lysophosphatidylcholines, sphingomyelins, and triacylglycerols (TAGs), however, other lipid subclasses were similar to controls. Analysis of individual TAG species revealed increased incorporation of saturated fatty acyl tails in serum of NAFLD cases. After adjusting for age, sex, body mass index, and PNPLA3 genotype, a combined panel of ten lipids predicted case or control status better than an area under the ROC curve of 0.83. Conclusions These preliminary results indicate that the serum lipidome differs in patients with NAFLD, compared to healthy controls, and suggest that assessing the desaturation state of TAGs or a specific lipid panel may be useful clinical tools for the diagnosis of NAFLD. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-021-01526-5.
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Affiliation(s)
- Yvonne N Flores
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. .,UCLA Center for Cancer Prevention and Control and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA. .,Unidad de Investigación Epidemiológica y en Servicios de Salud, Morelos, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, Mexico.
| | - Aryana T Amoon
- UCLA Center for Cancer Prevention and Control and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Baolong Su
- UCLA Lipidomics Laboratory, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Rafael Velazquez-Cruz
- Laboratorio de Genómica del Metabolismo Óseo, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, Mexico
| | - Paula Ramírez-Palacios
- Unidad de Investigación Epidemiológica y en Servicios de Salud, Morelos, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, Mexico
| | - Jorge Salmerón
- Centro de Investigación en Políticas, Población y Salud, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Berenice Rivera-Paredez
- Centro de Investigación en Políticas, Población y Salud, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Janet S Sinsheimer
- UCLA Department of Human Genetics and Computational Medicine, Los Angeles, CA, USA.,Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA
| | - Aldons J Lusis
- UCLA Department of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA.,UCLA Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Adriana Huertas-Vazquez
- UCLA Department of Medicine, Division of Cardiology, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Sammy Saab
- UCLA Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, Los Angeles, CA, USA.,Pfleger Liver Institute, UCLA David Geffen School of Medicine, Los Angeles, CA, USA
| | - Beth A Glenn
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,UCLA Center for Cancer Prevention and Control and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Folasade P May
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,UCLA Center for Cancer Prevention and Control and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.,UCLA Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, Los Angeles, CA, USA.,Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Kevin J Williams
- UCLA Lipidomics Laboratory, David Geffen School of Medicine, Los Angeles, CA, USA.,UCLA Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA, USA
| | - Roshan Bastani
- Department of Health Policy and Management, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,UCLA Center for Cancer Prevention and Control and UCLA-Kaiser Permanente Center for Health Equity, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Steven J Bensinger
- UCLA Lipidomics Laboratory, David Geffen School of Medicine, Los Angeles, CA, USA.,UCLA Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Los Angeles, CA, USA
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Prieto Ortiz JE, Sánchez Pardo S, Prieto Ortiz RG, Garzón Orjuela N, S Ford J, Eslava Schmalbach J. Comparison of shear wave elastography (supersonic) with liver biopsy in a cohort of patients from a medium-income country: an observational study. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:318-323. [PMID: 33213167 DOI: 10.17235/reed.2020.6816/2019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION shear-wave elastography is a non-invasive diagnostic test that calculates the degree of liver fibrosis by measuring liver elasticity. This technique was recently introduced in Colombia. Thus, cutoff points delineating the change between fibrosis stages (using the Metavir scale) have not been previously defined in our patient population. PATIENTS AND METHODS a retrospective study was performed of patients who had undergone two-dimensional shear-wave elastography (2D-SWE) and liver biopsy (LB) between June 2010 and June 2018 at a private outpatient hepatology center in Bogota, Colombia. We used a training dataset (subjects with time between biopsy and 2D-SWE of ≤ 6 months) to establish diagnostic cutoff values and a test dataset (subjects with time between biopsy and 2D-SWE of > 6 months) to validate our results. RESULTS a total of 453 subjects (training dataset, n = 153; test dataset, n = 300) were included. In the training dataset, the cutoff points were 7.6, 8.4, 9.5 and 10.9 kPa, and the areas under the curve were 0.75, 0.83, 0.89 and 0.94 for mild fibrosis, significant fibrosis, advanced fibrosis and cirrhosis, respectively. In the test dataset, the areas under the curve were 0.77, 0.78, 0.83 and 0.89 for mild fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis, respectively. CONCLUSION two-dimensional shear-wave elastography was reliable and useful for the non-invasive evaluation of liver fibrosis, particularly in patients with advanced fibrosis and cirrhosis. Cutoff points for fibrosis in a Hispanic population were described.
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Affiliation(s)
- Jhon Edison Prieto Ortiz
- Gastroenterology and Hepatology, Center for Research in Hepatic and Digestive Diseases (CEHYD), Colombia
| | | | - Robin Germán Prieto Ortiz
- General Surgery and Gantroenterology, Center for Research in Hepatic and Digestive Diseases (CEHYD), COLOMBIA
| | - Nathaly Garzón Orjuela
- Clinical Research Institute. School of Medicine, National University of Colombia, Colombia
| | - James S Ford
- School of Medicine , University of California, United States
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Dongiovanni P, Paolini E, Corsini A, Sirtori CR, Ruscica M. Nonalcoholic fatty liver disease or metabolic dysfunction-associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches. Eur J Clin Invest 2021; 51:e13519. [PMID: 33583033 DOI: 10.1111/eci.13519] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/10/2021] [Accepted: 02/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND A consensus of experts has proposed to replace the term nonalcoholic fatty liver disease (NAFLD), whose global prevalence is 25%, with metabolic dysfunction-associated fatty liver disease (MAFLD), to describe more appropriately the liver disease related to metabolic derangements. MAFLD is closely intertwined with type 2 diabetes, obesity, dyslipidaemia, all linked to a rise in the risk of cardiovascular disease (CVDs). Since controversy still stands on whether or not NAFLD/MAFLD raises the odds of CVD, the present review aims to evaluate the impact of NAFLD/MAFLD aetiologies on CV health and the potential correction by dietary and drug approaches. RESULTS Epidemiological studies indicate that NAFLD raises risk of fatal or non-fatal CVD events. NAFLD patients have a higher prevalence of arterial plaques and stiffness, coronary calcification, and endothelial dysfunction. Although genetic and environmental factors strongly contribute to NAFLD pathogenesis, a Mendelian randomization analysis indicated that the PNPLA3 genetic variant leading to NAFLD may not be causally associated with CVD risk. Among other genetic variants related to NAFLD, TM6SF2 appears to be protective, whereas MBOAT7 may favour venous thromboembolism. CONCLUSIONS NAFLD is correlated to a higher CVD risk which may be ameliorated by dietary interventions. This is not surprising, since new criteria defining MAFLD include other metabolic risk abnormalities fuelling development of serious adverse extrahepatic outcomes, for example CVD. The present lack of a targeted pharmacological approach makes the identification of patients with liver disease at higher CVD risk (eg diabetes, hypertension, obesity or high levels of C-reactive protein) of major clinical interest.
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Affiliation(s)
- Paola Dongiovanni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Erika Paolini
- General Medicine and Metabolic Diseases, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Alberto Corsini
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.,Multimedica IRCCS, Sesto San Giovanni (MI), Milan, Italy
| | - Cesare R Sirtori
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
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34
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Bellarosa C, Bedogni G, Bianco A, Cicolini S, Caroli D, Tiribelli C, Sartorio A. Association of Serum Bilirubin Level with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study of 1672 Obese Children. J Clin Med 2021; 10:2812. [PMID: 34202304 PMCID: PMC8268762 DOI: 10.3390/jcm10132812] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/17/2021] [Accepted: 06/21/2021] [Indexed: 12/12/2022] Open
Abstract
As in adults, obesity also plays a central role in the development of metabolic syndrome (MS) in children. Non-alcoholic fatty liver disease (NAFLD) is considered a manifestation of MS. Not only MS but also NAFLD seem to be inversely associated with serum bilirubin concentrations, an important endogenous tissue protector when only mild elevated. The aim of the study was to evaluate the association between serum bilirubin levels and the prevalence of MS and NAFLD in Italian obese children and adolescents. A retrospective cross-sectional study was performed in 1672 patients aged from 5 to 18 years. Clinical and laboratory parameters were assessed. NAFLD was measured by liver ultrasonography. The study was approved by the Ethical Committee of the Istituto Auxologico Italiano (research project code 1C021_2020, acronym BILOB). MS was present in 24% and fatty liver (FL) in 38% of this population. Bilirubin was not associated with FL and MS as a whole, but it was inversely associated only with selected components of MS, i.e., large WC, high blood pressure and high triglycerides. Our data suggest that bilirubin is not protective against MS and NAFLD in the presence of severe obesity.
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Affiliation(s)
| | - Giorgio Bedogni
- Italian Liver Foundation, 34149 Trieste, Italy; (G.B.); (A.B.); (C.T.)
| | - Annalisa Bianco
- Italian Liver Foundation, 34149 Trieste, Italy; (G.B.); (A.B.); (C.T.)
- Life Science Department, University of Trieste, 34127 Trieste, Italy
| | - Sabrina Cicolini
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, 28824 Verbania, Italy; (S.C.); (D.C.); (A.S.)
| | - Diana Caroli
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, 28824 Verbania, Italy; (S.C.); (D.C.); (A.S.)
| | - Claudio Tiribelli
- Italian Liver Foundation, 34149 Trieste, Italy; (G.B.); (A.B.); (C.T.)
| | - Alessandro Sartorio
- Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-Endocrinological Research, 28824 Verbania, Italy; (S.C.); (D.C.); (A.S.)
- Istituto Auxologico Italiano, IRCCS, Division of Auxology and Metabolic Diseases, 28824 Verbania, Italy
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35
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Zhu JH. COVID-19 mRNA vaccines and their applications in chronic liver diseases. CANADIAN LIVER JOURNAL 2021; 4:110-112. [DOI: 10.3138/canlivj-2020-0001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 01/11/2021] [Indexed: 11/20/2022]
Affiliation(s)
- Julie H Zhu
- Division of Digestive Care and Endoscopy, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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36
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Andreadou I, Daiber A, Baxter GF, Brizzi MF, Di Lisa F, Kaludercic N, Lazou A, Varga ZV, Zuurbier CJ, Schulz R, Ferdinandy P. Influence of cardiometabolic comorbidities on myocardial function, infarction, and cardioprotection: Role of cardiac redox signaling. Free Radic Biol Med 2021; 166:33-52. [PMID: 33588049 DOI: 10.1016/j.freeradbiomed.2021.02.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 02/03/2021] [Accepted: 02/06/2021] [Indexed: 02/06/2023]
Abstract
The morbidity and mortality from cardiovascular diseases (CVD) remain high. Metabolic diseases such as obesity, hyperlipidemia, diabetes mellitus (DM), non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) as well as hypertension are the most common comorbidities in patients with CVD. These comorbidities result in increased myocardial oxidative stress, mainly from increased activity of nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, mitochondria as well as downregulation of antioxidant defense systems. Oxidative and nitrosative stress play an important role in ischemia/reperfusion injury and may account for increased susceptibility of the myocardium to infarction and myocardial dysfunction in the presence of the comorbidities. Thus, while early reperfusion represents the most favorable therapeutic strategy to prevent ischemia/reperfusion injury, redox therapeutic strategies may provide additive benefits, especially in patients with heart failure. While oxidative and nitrosative stress are harmful, controlled release of reactive oxygen species is however important for cardioprotective signaling. In this review we summarize the current data on the effect of hypertension and major cardiometabolic comorbidities such as obesity, hyperlipidemia, DM, NAFLD/NASH on cardiac redox homeostasis as well as on ischemia/reperfusion injury and cardioprotection. We also review and discuss the therapeutic interventions that may restore the redox imbalance in the diseased myocardium in the presence of these comorbidities.
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Affiliation(s)
- Ioanna Andreadou
- Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
| | - Andreas Daiber
- Department of Cardiology 1, Molecular Cardiology, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany; Partner Site Rhine-Main, German Center for Cardiovascular Research (DZHK), Langenbeckstr, Germany.
| | - Gary F Baxter
- Division of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, United Kingdom
| | | | - Fabio Di Lisa
- Department of Biomedical Sciences, University of Padova, Italy; Neuroscience Institute, National Research Council of Italy (CNR), Padova, Italy
| | - Nina Kaludercic
- Neuroscience Institute, National Research Council of Italy (CNR), Padova, Italy
| | - Antigone Lazou
- Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece
| | - Zoltán V Varga
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary
| | - Coert J Zuurbier
- Laboratory of Experimental Intensive Care Anesthesiology, Department Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Rainer Schulz
- Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany.
| | - Péter Ferdinandy
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary
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Satapathy SK, Marella HK, Heda RP, Ganguli S, Kirthi Reddy Y, Podila PSB, Clark I, Maliakkal B. African Americans have a distinct clinical and histologic profile with lower prevalence of NASH and advanced fibrosis relative to Caucasians. Eur J Gastroenterol Hepatol 2021; 33:388-398. [PMID: 32317586 DOI: 10.1097/meg.0000000000001735] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Racial/ethnic disparities have been reported in the prevalence of nonalcoholic fatty liver disease (NAFLD). Thus, we aimed to understand the inter-ethnic clinical, biochemical, and histological differences in a large cohort of Caucasians and African-Americans (AA). METHODS Laboratory and liver biopsy data of 942 NAFLD patients were retrospectively analyzed. Nine hundred seven patients were included in the analysis: 677 (74.6%) Caucasians and 230 (25.3%) AA. RESULTS AA had higher mean BMI compared to Caucasians (42.6 ± 9.5 vs. 39 ± 8.6 kg/m2). The prevalence of nonalcoholic steatohepatitis (NASH), defined by NAFLD activity score (NAS . 5), was higher in the Caucasians (n = 67) compared to AA (n = 7) (9.8% vs. 3%, P = 0.0007). One hundred fifteen patients (12.8%) had advanced fibrosis: 109 (16.2%) Caucasians and six (2.6%) AA. No AA patients had stage 4 fibrosis or cirrhosis. Multivariate logistic regression analysis revealed advanced fibrosis was significantly associated with age at liver biopsy (OR 1.03, 95% CI 1.0.1.1, P = 0.017, lower platelet count (OR 0.99, 95% CI 0.98.0.99, P = <0.0001), AST/ALT ratio (OR 5.19, 95% CI 2.9.9.2, P <0.0001) and Caucasian race (OR 7.49, 95% CI 2.53.22.2, P = 0.0003). Advanced fibrosis in AA was predicted by lower platelet count and AST/ALT ratio. Whereas Advanced fibrosis in Caucasians was predicted by age at biopsy, lower platelet count and AST/ALT ratio. CONCLUSION The AA have a distinct clinical and histologic phenotype. Caucasians have a significantly greater proportion of NASH and are eight times more likely to develop advanced fibrosis than AA.
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Affiliation(s)
- Sanjaya K Satapathy
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Science Center, Memphis, Tennessee
- Division of Hepatology and Liver Transplantation, Sandra Atlas Bass Center for Liver Diseases, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, Manhasset, New York
| | | | - Rajiv P Heda
- University of Tennessee Health Science Center, College of Medicine, Methodist University Hospital, Memphis, Tennessee
| | - Surosree Ganguli
- Department of Medicine, University of Louisville, Louisville, Kentucky
| | - Yala Kirthi Reddy
- Department of Medicine, University of Tennessee Health Science Center
| | - Pradeep S B Podila
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Ian Clark
- Department of Pathology, Methodist University Hospital, Memphis, Tennessee, USA
| | - Benedict Maliakkal
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Science Center, Memphis, Tennessee
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38
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Wijarnpreecha K, Aby ES, Panjawatanan P, Lapumnuaypol K, Cheungpasitporn W, Lukens FJ, Harnois DM, Ungprasert P. Modest alcohol consumption and risk of advanced liver fibrosis in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Ann Gastroenterol 2021; 34:568-574. [PMID: 34276197 PMCID: PMC8276361 DOI: 10.20524/aog.2021.0612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 12/30/2020] [Indexed: 11/18/2022] Open
Abstract
Background Recent studies have suggested an association between modest alcohol consumption and a decreased risk of advanced liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) although the results are inconsistent. The current systematic review and meta-analysis was conducted to comprehensively investigate this possible association by identifying all the relevant studies and combining their results. Methods A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through February 2019 to identify all cross-sectional studies that compared the prevalence of advanced liver fibrosis among NAFLD patients who were modest alcohol drinkers to NAFLD patients who were non-drinkers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. Results A total of 6 studies with 8,936 participants fulfilled the eligibility criteria and were included in the meta-analysis. The risk of advanced liver fibrosis among patients with NAFLD who were modest alcohol drinkers was significantly lower compared to patients with NAFLD who were non-drinkers with a pooled odds ratio of 0.51 (95% confidence interval [CI] 0.35-0.75; I2 47%). The funnel plot was symmetric and was not suggestive of publication bias. Conclusion A significantly lower risk of advanced liver fibrosis was observed among NAFLD patients who were modest alcohol drinkers compared to non-drinkers in this meta-analysis.
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Affiliation(s)
- Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA (Karn Wijarnpreecha, Denise M. Harnois)
| | - Elizabeth S Aby
- Department of Medicine, University of California at Los Angeles, CA, USA (Elizabeth S. Aby, Frank J. Lukens)
| | - Panadeekarn Panjawatanan
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (Panadeekarn Panjawatanan)
| | - Kamolyut Lapumnuaypol
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA (Kamolyut Lapumnuaypol)
| | - Wisit Cheungpasitporn
- Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, USA (Wisit Cheungpasitporn)
| | - Frank J Lukens
- Department of Medicine, University of California at Los Angeles, CA, USA (Elizabeth S. Aby, Frank J. Lukens)
| | - Denise M Harnois
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA (Karn Wijarnpreecha, Denise M. Harnois)
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand (Patompong Ungprasert)
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Nyberg LM, Cheetham TC, Patton HM, Yang SJ, Chiang KM, Caparosa SL, Stern JA, Nyberg AH. The Natural History of NAFLD, a Community-Based Study at a Large Health Care Delivery System in the United States. Hepatol Commun 2021; 5:83-96. [PMID: 33437903 PMCID: PMC7789841 DOI: 10.1002/hep4.1625] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 09/15/2020] [Accepted: 09/26/2020] [Indexed: 12/20/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. However, the natural history of NAFLD is incomplete. This is a retrospective cohort study of patients identified with NAFLD by diagnosis codes in a large, community-based health care delivery system. The objectives were (1) to follow patients from initial NAFLD presentation through progression to cirrhosis and/or decompensated cirrhosis to liver cancer, liver transplant, and death for up to 10 years; and (2) to conduct disease progression analysis restricted to patients with NAFLD identified as having diabetes at baseline. A total of 98,164 patients with full NAFLD and 26,488 with diabetes were divided into three baseline prevalent states: (1) no cirrhosis, (2) compensated cirrhosis, and (3) decompensated cirrhosis. In baseline patients without cirrhosis, annual rates of compensated cirrhosis, decompensated cirrhosis, and death were 0.28%, 0.31%, and 0.63% per year, respectively. With baseline compensated cirrhosis, the annual rates of decompensation and death were 2.4% and 6.7% per year. Finally, in those with decompensated cirrhosis at baseline, the death rate was 8.0% per year. In those without cirrhosis and with cirrhosis at baseline, the rates of liver cancer and death were increased approximately 2-fold in the diabetic subpopulation compared with the full NAFLD cohort. Age and comorbidities increased with increasing disease severity. Cox proportional hazards regression analysis showed that cirrhosis was strongly associated with death and liver cancer, and that diabetes was associated with a significant increase in the hazard of both liver cancer and death (2.56 [2.04-3.20] and 1.43 [1.35-1.52]), respectively. Conclusion: The findings of this community-based study further our understanding of the natural history of NAFLD and demonstrate that diabetes is a major factor in the progression of this disease.
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Affiliation(s)
- Lisa M Nyberg
- Gastroenterology/HepatologySouthern California Permanente Medical GroupSan DiegoCAUSA
| | | | - Heather M Patton
- Gastroenterology/HepatologySouthern California Permanente Medical GroupSan DiegoCAUSA
| | - Su-Jau Yang
- Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaCAUSA
| | | | - Susan L Caparosa
- Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaCAUSA
| | - Julie A Stern
- Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaCAUSA
| | - Anders H Nyberg
- Gastroenterology/HepatologySouthern California Permanente Medical GroupSan DiegoCAUSA
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40
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Lavekar AS, Deshpande A, Raje D. Comparison of knowledge and awareness between consultant physicians and resident doctors about non-alcoholic fatty liver disease. Clin Exp Hepatol 2020; 6:374-383. [PMID: 33511287 PMCID: PMC7816641 DOI: 10.5114/ceh.2020.102152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 10/03/2020] [Indexed: 11/17/2022] Open
Abstract
AIM OF THE STUDY Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease and is commonly associated with diabetes mellitus, dyslipidaemia, hypertension and obesity. These illnesses are usually treated by physicians, and hence they need to stay updated on NAFLD. The aim of the study was to assess and compare the knowledge and awareness about NAFLD among consultant physicians and resident doctors. MATERIAL AND METHODS A questionnaire concerning epidemiology, risk factors, complications, diagnostic methods, management options, progression and screening of NAFLD was given to the consultant physicians and resident doctors and their responses were sought. The comparison of responses was carried out between residents and consultants using Pearson's χ2 test. RESULTS A total of 240 doctors participated in the study with 60 resident doctors and 180 consultant physicians. 45% of the total participants did not consider NAFLD as a major health hazard. Consultants had better knowledge than residents about the prevalence of NAFLD, and the risks due to various factors. Also they had better knowledge about non-invasive diagnostic modalities. Resident doctors advocated use of antioxidants more than consultants. There was no statistically significant difference of perception between residents and physicians about association of NAFLD with diabetes and obesity, diet advice, dietary modification and exercise, usage of medications, avoidance of hepatotoxic drugs and alcohol. CONCLUSIONS This study revealed that physicians participating in our survey appreciate the prevalence of NAFLD but are unaware of the seriousness and the optimal management. This has implications for targeting 'at-risk' populations and appropriate referral of patients to gastroenterology/hepatology clinics.
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Affiliation(s)
| | - Aditi Deshpande
- Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India
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41
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Tanaka S, Fujishiro M, Watanabe K, Imatake K, Suzuki Y, Abe M, Ishihara H, Tani S. Effect of Adult Weight Gain on Non-Alcoholic Fatty Liver Disease and Its Association with Anthropometric Parameters in the Lean Japanese Population. Diagnostics (Basel) 2020; 10:diagnostics10110863. [PMID: 33113887 PMCID: PMC7690736 DOI: 10.3390/diagnostics10110863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 10/21/2020] [Accepted: 10/21/2020] [Indexed: 01/01/2023] Open
Abstract
Limited data are available on the prevalence of non-alcoholic fatty liver disease (NAFLD) and its association with adult weight gain (AWG) in the lean population. This study aimed to determine the prevalence of NAFLD and to investigate whether AWG is associated with NAFLD in the lean Japanese population. We retrospectively analyzed patients who underwent abdominal ultrasonography as part of the annual health checkup between January 2019 and December 2019. Participants were classified into two groups: those with AWG ≥ 10 kg (AWG group, n = 497), and those without gain (non-AWG group, n = 3006). To adjust for the confounding effects, we generated 482 pairs using 1:1 propensity score matching. The associations between AWG and NAFLD, anthropometric parameters and NAFLD were investigated using univariate logistic regression analysis. We identified NAFLD in 197 (5.6%) participants. AWG was significantly associated with NAFLD (odds ratio (OR), 1.81; p = 0.003). Waist circumference was significantly associated with NAFLD in both the AWG (OR, 1.24; p < 0.001) and non-AWG groups (OR, 1.17; p < 0.001). The association between body mass index and NAFLD existed in the former group (OR, 1.76; p < 0.001), but was not significant in the latter group. AWG is a risk factor for NAFLD even in the lean Japanese population, and associations between anthropometric parameters and NAFLD become stronger if AWG coexists.
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Affiliation(s)
- Sho Tanaka
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan; (S.T.); (M.A.)
- Department of Internal Medicine, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan
| | - Midori Fujishiro
- Department of Internal Medicine, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan; (K.W.); (H.I.)
- Correspondence:
| | - Kentaro Watanabe
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan; (K.W.); (H.I.)
| | - Kazuhiro Imatake
- Department of Health Planning Center, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan; (K.I.); (Y.S.); (S.T.)
| | - Yasuyuki Suzuki
- Department of Health Planning Center, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan; (K.I.); (Y.S.); (S.T.)
- Department of Cardiology, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan
| | - Masanori Abe
- Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan; (S.T.); (M.A.)
| | - Hisamitsu Ishihara
- Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan; (K.W.); (H.I.)
| | - Shigemasa Tani
- Department of Health Planning Center, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan; (K.I.); (Y.S.); (S.T.)
- Department of Cardiology, Nihon University Hospital, 1-6 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-8309, Japan
- Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan
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Tobari M, Hashimoto E. Characteristic Features of Nonalcoholic Fatty Liver Disease in Japan with a Focus on the Roles of Age, Sex and Body Mass Index. Gut Liver 2020; 14:537-545. [PMID: 31887811 PMCID: PMC7492496 DOI: 10.5009/gnl19236] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 09/08/2019] [Accepted: 09/16/2019] [Indexed: 02/06/2023] Open
Abstract
This review provides an update on the characteristics of nonalcoholic fatty liver disease (NAFLD), with a focus on the effects of age, sex, and body mass index. Age is a risk factor for NAFLD progression; however, extremely old patients have unique features, namely, the associations between metabolic comorbidities and NAFLD are weaker and NAFLD is not a risk factor for mortality. The prevalence of NAFLD is higher in men than in premenopausal women, whereas the reverse is true after menopause. Thus, before menopause, estrogen may have protective effects against NAFLD. Our hospital data showed that over 25% of male patients with NAFLD and almost 40% of female patients with NAFLD, especially elderly patients, were nonobese. Although histological steatosis and activity were associated with body mass index, the prevalence of nonalcoholic steatohepatitis was not. The prevalence of advanced fibrosis showed a significant sex difference. Advanced fibrosis was significantly more frequent among severely obese men but the prevalence was lower among severely obese women. This difference could be because a substantial proportion of severely obese women were premenopausal; thus, estrogen may have much stronger effects on the development of fibrosis than on obesity. Further studies are required to develop tailored management strategies.
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Affiliation(s)
- Maki Tobari
- Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, Japan
| | - Etsuko Hashimoto
- Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan
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Patel P, Muller C, Paul S. Racial disparities in nonalcoholic fatty liver disease clinical trial enrollment: A systematic review and meta-analysis. World J Hepatol 2020; 12:506-518. [PMID: 32952877 PMCID: PMC7475777 DOI: 10.4254/wjh.v12.i8.506] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 07/09/2020] [Accepted: 07/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has a heterogeneous distribution across racial and ethnic groups, with a disproportionate burden among Hispanics. Although there are currently no approved therapies for treatment of NAFLD, several therapies have been investigated in clinical trials.
AIM To analyze the inclusion of racial and ethnic minority groups in clinical trials for NAFLD.
METHODS We performed a systematic review of North American, English-language, prospective studies for NAFLD therapies published from 2005 to 2019. Racial and ethnic enrollment data were recorded for each eligible study. Meta-analysis was performed to compute pooled prevalence of different racial and ethnic groups, followed by further subgroup analyses. These analyses were based on diagnosis of non-alcoholic steatohepatitis (NASH) and timing of study on enrollment by ethnicity. Descriptive statistics were performed to compare racial and ethnic study enrollment to previously reported NAFLD population prevalence.
RESULTS Thirty-eight studies met criteria for inclusion in the systematic review. When reported, median age of enrolled subjects was 49 years (range 41.5-58) with 56% female participants. NAFLD was defined through biopsy findings in 79% (n = 30) of the studies. Of the included articles, treatment modalities ranged from medications (n = 28, 74%), lifestyle interventions (n = 5, 13%), bariatric surgery (n = 4, 11%) and phlebotomy (n = 1, 2%). Twenty-eight studies (73%) included racial and/or ethnic demographic information, while only 17 (45%) included information regarding Hispanic participation. Of the 2983 patients enrolled in all eligible trials, a total of only 346 (11.6%) Hispanic participants was reported. Meta-analysis revealed a pooled Hispanic prevalence of 24.3% (95% confidence interval 16.6-32.0, I2 94.6%) among studies documenting Hispanic enrollment. Hispanic enrollment increased over time from 15% from 2005-2014 to 37% from 2015-2019.
CONCLUSION In a meta-analysis of NAFLD trials, documentation of racial/ethnic demographic data occurred in less than half of studies. Standardization of reporting of race/ethnicity and targeted interventions toward minority recruitment are needed to improve diversity of enrollment.
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Affiliation(s)
- Parita Patel
- Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medical Center, Chicago, IL 60637, United States
| | - Charles Muller
- Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medical Center, Chicago, IL 60637, United States
| | - Sonali Paul
- Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medical Center, Chicago, IL 60637, United States
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Samji NS, Snell PD, Singal AK, Satapathy SK. Racial Disparities in Diagnosis and Prognosis of Nonalcoholic Fatty Liver Disease. Clin Liver Dis (Hoboken) 2020; 16:66-72. [PMID: 32922753 PMCID: PMC7474141 DOI: 10.1002/cld.948] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 01/29/2020] [Accepted: 02/11/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Naga Swetha Samji
- Department of Internal MedicineTennova Cleveland HospitalClevelandTN
| | - Peter D. Snell
- Department of Internal MedicineUniversity of Tennessee Health Science CenterMemphisTN
| | - Ashwani K. Singal
- Department of Internal MedicineUniversity of South Dakota Sanford School of Medicine and Avera Transplant InstituteSioux FallsSD
| | - Sanjaya K. Satapathy
- Division of Hepatology, Sandra Atlas Bass Center for Liver DiseasesNorthwell HealthManhassetNY
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Eslam M, Sanyal AJ, George J. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology 2020; 158:1999-2014.e1. [PMID: 32044314 DOI: 10.1053/j.gastro.2019.11.312] [Citation(s) in RCA: 2142] [Impact Index Per Article: 428.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 10/27/2019] [Accepted: 11/05/2019] [Indexed: 12/02/2022]
Abstract
Fatty liver associated with metabolic dysfunction is common, affects a quarter of the population, and has no approved drug therapy. Although pharmacotherapies are in development, response rates appear modest. The heterogeneous pathogenesis of metabolic fatty liver diseases and inaccuracies in terminology and definitions necessitate a reappraisal of nomenclature to inform clinical trial design and drug development. A group of experts sought to integrate current understanding of patient heterogeneity captured under the acronym nonalcoholic fatty liver disease (NAFLD) and provide suggestions on terminology that more accurately reflects pathogenesis and can help in patient stratification for management. Experts reached consensus that NAFLD does not reflect current knowledge, and metabolic (dysfunction) associated fatty liver disease "MAFLD" was suggested as a more appropriate overarching term. This opens the door for efforts from the research community to update the nomenclature and subphenotype the disease to accelerate the translational path to new treatments.
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
| | - Arun J Sanyal
- Virginia Commonwealth University School of Medicine, Richmond, Virginia.
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
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Kallwitz E, Tayo BO, Kuniholm MH, Daviglus M, Zeng D, Isasi CR, Cotler SJ. Association of HSD17B13 rs72613567:TA with non-alcoholic fatty liver disease in Hispanics/Latinos. Liver Int 2020; 40:889-893. [PMID: 31965669 DOI: 10.1111/liv.14387] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic/Latinos and rates of NAFLD vary among Hispanics from different background groups. Genetic variants and continental ancestry contribute to NAFLD disparities among Hispanics. We evaluated two newly identified NAFLD-associated single nucleotide polymorphisms of HSD17B13, rs72613567:TA and rs62305723:A in Hispanics/Latinos. METHODS Clinical data, genotypes of variants of interest and estimates of continental ancestry were extracted from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) database, which includes a cohort of 16 415 US Hispanic/Latinos. Surrogate endpoints for NAFLD were suspected NAFLD based on unexplained aminotransferase elevation, continuous ALT levels and FIB-4 scores to estimate hepatic fibrosis. RESULTS In all, 9342 participants were included for analysis. The rs72613567:TA allele was found in 15.3% and the rs62305723:A allele was identified in 4.5% of HCHS/SOL participants. rs72613567:TA was less frequent in persons with vs without suspected NAFLD (12.4% vs 15.7%, P < .001) and rs72613567:TA was associated with lower FIB-4 scores (P = .01). For persons with the NAFLD-associated PNPLA3 rs738409:G allele, the presence of rs72613567:TA was associated with a lower rate of suspected NAFD (odds ratio = 0.76, P < .001). rs72613567:TA was less frequent in Hispanic/Latino background groups with higher rates of suspected NAFLD. The rs62305723:A allele was not associated with suspected NAFLD or FIB-4 score. CONCLUSION The rs72613567:TA allele is associated with lower rates of suspected NAFLD and lower FIB-4 scores among Hispanic/Latinos and with lower rates of suspected NAFLD in persons with the PNPLA3 rs738409:G allele. The rs72613567:TA allele contributes to NAFLD disparities among Hispanic/Latino background groups.
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Affiliation(s)
- Eric Kallwitz
- Department of Medicine, Loyola University Medical Center, Maywood, IL, USA
| | - Bamidele O Tayo
- Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA
| | - Mark H Kuniholm
- School of Public Health, State University of New York, Albany, NY, USA
| | - Martha Daviglus
- Institute of Minority Health Research, University of Illinois, Chicago, IL, USA
| | - Donglin Zeng
- Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA
| | - Carmen R Isasi
- Department of Epidemiology and Population Health, Einstein College of Medicine, New York, NY, USA
| | - Scott J Cotler
- Department of Medicine, Loyola University Medical Center, Maywood, IL, USA
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Lin YC, Wu CC, Ni YH. New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease. Front Pediatr 2020; 8:603654. [PMID: 33363067 PMCID: PMC7755886 DOI: 10.3389/fped.2020.603654] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic or recently re-defined metabolic associated fatty liver disease (MAFLD), a spectrum of progressive hepatic disease, has become a public health issue in obese children and adolescents. MAFLD is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subject will develop MAFLD. Different ethnic/racial groups display differences in MAFLD prevalence, indicating genetic factor plays a role. In the past two decades, sequence variations in genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, etc. have been shown to confer susceptibility to MAFLD in children and adults. This review article provides an updated viewpoint of genetic predictors related to pediatric MAFLD. We discuss whether these susceptible genes can be clinically used for risk stratification and personalized care. Understanding human genetics and molecular mechanisms can give important information not only for prediction of risk but also on how to design drugs. In view of current epidemic of MAFLD worldwide, it is necessary to identify which children with MAFLD progress rapidly and need earlier intervention. In the future, a comprehensive analysis of individualized genetic and environmental factors may help assess the risk of children with MAFLD and personalize their treatment.
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Affiliation(s)
- Yu-Cheng Lin
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Department of Healthcare Administration, Oriental Institute of Technology, New Taipei City, Taiwan
| | - Chi-Chien Wu
- Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Yen-Hsuan Ni
- Departments of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
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Kallwitz ER, Tayo BO, Kuniholm MH, Cai J, Daviglus M, Cooper RS, Cotler SJ. American Ancestry Is a Risk Factor for Suspected Nonalcoholic Fatty Liver Disease in Hispanic/Latino Adults. Clin Gastroenterol Hepatol 2019; 17:2301-2309. [PMID: 30743004 DOI: 10.1016/j.cgh.2019.02.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 01/27/2019] [Accepted: 02/03/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) disproportionally affects Hispanic/Latino populations. However, the magnitude varies among Hispanic/Latino ethnic groups. We investigated the mechanisms of these disparities. METHODS We examined associations of NAFLD-associated genetic variants and continental ancestry with suspected NAFLD, levels of alanine aminotransferase (ALT), and liver fibrosis using data from the Hispanic Community Health Study/Study of Latinos-a population-based study of Hispanic/Latino adults in the United States. We evaluated data from 16,415 Hispanic/Latino adults in 4 cities from 2008 through 2011. Subjects suspected of having NAFLD or liver fibrosis were identified based on unexplained increases in levels of aminotransferases and FIB-4 score, respectively. RESULTS Among the 9342 participants with available genetic and aminotransferase data, the PNPLA3 G allele (odds ratio [OR], 1.53; 95% CI, 1.41-1.66), TM6SF2 T allele (OR, 1.41; 95% CI, 1.20-1.67), and PPP1R3B G allele (OR, 1.16; 95% CI, 1.06-1.28) were associated with suspected NAFLD. PNPLA3 G was also associated with increased levels of ALT, except in participants with Dominican and South American backgrounds, and with liver fibrosis. The frequency of PNPLA3 G was high (41%) and TM6SF2 T (5%) was low in Hispanic/Latinos. PNPLA3 G frequency differed among Hispanic background groups with the highest proportion in Mexicans (52%) and the lowest proportion in Dominicans (23%). After adjustment for demographic, clinical, and behavioral factors, as well as PNPLA3 G, TM6SF2 T, and PPP1R3B G, American ancestry had a positive association with level of ALT (r = 6.61%; P < .001), whereas African (r = -3.84%; P < .001) and European (r = -4.31%; P < .001) ancestry were inversely associated with level of ALT. CONCLUSIONS American ancestry and PNPLA3 G are independent predictors of ALT levels in US Hispanic/Latinos and may in part explain NAFLD disparities in US Hispanic/Latinos.
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Affiliation(s)
- Eric R Kallwitz
- Division of Hepatology, Loyola University Medical Center, Maywood, Illinois.
| | - Bamidele O Tayo
- Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
| | | | - Jianwen Cai
- UNC Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina
| | - Martha Daviglus
- Institute for Minority Health Research, University of Illinois, Chicago, Illinois
| | - Richard S Cooper
- Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois
| | - Scott J Cotler
- Division of Hepatology, Loyola University Medical Center, Maywood, Illinois
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Agbim U, Carr RM, Pickett-Blakely O, Dagogo-Jack S. Ethnic Disparities in Adiposity: Focus on Non-alcoholic Fatty Liver Disease, Visceral, and Generalized Obesity. Curr Obes Rep 2019; 8:243-254. [PMID: 31144261 PMCID: PMC6662200 DOI: 10.1007/s13679-019-00349-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Excessive adiposity has become a public health problem worldwide, contributing to the rise in obesity-related diseases and associated morbidity and mortality. This review details the relative significance of race/ethnicity as it pertains to adiposity and non-alcoholic fatty liver disease (NAFLD). RECENT FINDINGS Fat distribution remains a more reliable measure of adiposity than anthropometric measures, with visceral adipose tissue (VAT) associated with increased risk of cardiometabolic disease. While obesity is the most common risk factor for NAFLD, the racial/ethnic prevalence of obesity does not completely parallel NAFLD risk. Combating racial/ethnic disparities in obesity requires understanding differential risk among various groups. Hispanics are disproportionally impacted by NAFLD and have high rates of obesity, VAT, and insulin resistance (IR). This contrasts with Blacks, who have high prevalence of obesity and IR, accompanied by a paradoxically favorable lipid profile and low prevalence of VAT and NAFLD. Many features of adiposity and NAFLD are mediated by genetic and environmental factors, the latter being modifiable and the focus of interventions.
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Affiliation(s)
- Uchenna Agbim
- Division of Transplant Surgery, Department of Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Rotonya M Carr
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Octavia Pickett-Blakely
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sam Dagogo-Jack
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Tennessee Health Science Center, 920 Madison Avenue, Suite 300A, Memphis, TN, 38163, USA.
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