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Powers C, Gunabushanam V, Centonze L, Humar A. Current perspectives on living donor selection in liver transplantation. Updates Surg 2025:10.1007/s13304-025-02131-2. [PMID: 39979551 DOI: 10.1007/s13304-025-02131-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 02/04/2025] [Indexed: 02/22/2025]
Abstract
The careful selection of donors is crucial to achieving a successful outcome in living donor liver transplantation. The evaluation process involves obtaining a comprehensive medical history and pertinent laboratory testing, evaluating surgical anatomy using cross-sectional radiologic imaging and understanding donor motivation and psycho social considerations. This review outlines the evaluation of a potential living liver donor and discussed frequently encountered special considerations that may need to be addressed by the transplant team.
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Affiliation(s)
- Colin Powers
- Division of Transplant Surgery, Starzl Transplantation Institute, University of Pittsburgh Medical Center, UPMC Montefiore N725, 3459 Fifth Av, Pittsburgh, PA, 15213, USA
| | - Vikraman Gunabushanam
- Division of Transplant Surgery, Starzl Transplantation Institute, University of Pittsburgh Medical Center, UPMC Montefiore N725, 3459 Fifth Av, Pittsburgh, PA, 15213, USA
| | - Leonardo Centonze
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Abhinav Humar
- Division of Transplant Surgery, Starzl Transplantation Institute, University of Pittsburgh Medical Center, UPMC Montefiore N725, 3459 Fifth Av, Pittsburgh, PA, 15213, USA.
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Fu Y, Wang C, Gao Z, Liao Y, Peng M, Fu F, Li G, Su D, Guo J, Shan Y. Microbes: Drivers of Chenpi manufacturing, biotransformation, and physiological effects. Food Chem 2025; 464:141631. [PMID: 39454433 DOI: 10.1016/j.foodchem.2024.141631] [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: 05/27/2024] [Revised: 09/16/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024]
Abstract
Chenpi holds a rich history of both edible and medicinal applications worldwide, garnering increased attention from researchers in recent years due to its diverse physiological effects. While current research predominantly exploresed its chemical composition and physiological effects, there remains a notable gap in knowledge concerning its manufacturing, characteristic chemical substances, and the underlying mechanisms driving its physiological effects. In this review, the impacts of microbes on the manufacturing, biotransformation, and physiological effects of Chenpi were summarized, as well as the present status of product development. Furthermore, this review engaged in an in-depth discussion highlighting the challenges and shortcomings in recent research, while proposing potential directions and prospects. Additionally, the claim that "The longer the aging, the better the quality" of Chenpi was scientifically evaluated for the first time, providing a solid theoretical foundation for advancing the Chenpi industry.
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Affiliation(s)
- Yanjiao Fu
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Chao Wang
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Zhipeng Gao
- Fisheries College, Hunan Agricultural University, Changsha 410128, China
| | - Yanfang Liao
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Mingfang Peng
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Fuhua Fu
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Gaoyang Li
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Donglin Su
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China
| | - Jiajing Guo
- Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China.
| | - Yang Shan
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China; Hunan Agriculture Product Processing Institute; Dongting Laboratory; Hunan Academy of Agricultural Sciences, Changsha 410125, China.
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3
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Jo S, Kim JM, Li M, Kim HS, An YJ, Park S. TAT as a new marker and its use for noninvasive chemical biopsy in NASH diagnosis. Mol Med 2024; 30:232. [PMID: 39592957 PMCID: PMC11590374 DOI: 10.1186/s10020-024-00992-8] [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: 09/04/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Early diagnosis of Nonalcoholic steatohepatitis (NASH) is crucial to prevent its progression to hepatocellular carcinoma, but its gold standard diagnosis still requires invasive biopsy. Here, a new marker-based noninvasive chemical biopsy approach is introduced that uses urine-secreted tyrosine metabolites. METHODS We first identified NASH-specific decrease in TAT expression, the first enzyme in the tyrosine degradation pathway (TDP), by employing exometabolome-transcriptome correlations, single-cell RNA -seq, and tissue staining on human NASH patient samples. A selective extrahepatic monitoring of the TAT activity was established by the chemical biopsy exploiting the enzyme's metabolic conversion of D2-tyrosine into D2-4HPP. The approach was applied to a NASH mouse model using the methionine-choline deficient diet, where urine D2-4HPP level was measured with a specific LC-MS detection, following oral administration of D2-tyrosine. RESULTS The noninvasive urine chemical biopsy approach could effectively differentiate NASH from normal mice (normal = 14, NASH = 15, p = 0.0054), correlated with the NASH pathology and TAT level decrease observed with immunostaining on the liver tissue. In addition, we showed that the diagnostic differentiation could be enhanced by measuring the downstream metabolites of TDP. The specificity of the TAT and the related TDP enzymes in NASH were also addressed in other settings employing high fat high fructose mouse NASH model and human obesity vs. NASH cohort. CONCLUSIONS Overall, we propose TAT and TDP as pathology-relevant markers for NASH and present the urine chemical biopsy as a noninvasive modality to evaluate the NASH-specific changes in urine that may help the NASH diagnosis.
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Affiliation(s)
- Sihyang Jo
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak- Ro 1, Gwanak-gu, Seoul, 08826, Republic of Korea
| | - Jin-Mo Kim
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak- Ro 1, Gwanak-gu, Seoul, 08826, Republic of Korea
| | - Minshu Li
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak- Ro 1, Gwanak-gu, Seoul, 08826, Republic of Korea
| | - Han Sun Kim
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak- Ro 1, Gwanak-gu, Seoul, 08826, Republic of Korea
- Department of Biochemistry, College of Medicine, Dongguk University, Gyeongju, 38066, Republic of Korea
| | - Yong Jin An
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak- Ro 1, Gwanak-gu, Seoul, 08826, Republic of Korea.
| | - Sunghyouk Park
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Gwanak- Ro 1, Gwanak-gu, Seoul, 08826, Republic of Korea.
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Duan H, Ding Y, Cheng Z, Cai L, Tong Y, Che F, Han Z, Li F, Wang Q, Geng X. Low serum alanine aminotransferase (ALT) levels are associated with poor outcomes in acute ischemic stroke patients regardless of age. Brain Res 2024; 1842:149130. [PMID: 39048033 DOI: 10.1016/j.brainres.2024.149130] [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: 04/29/2024] [Revised: 07/10/2024] [Accepted: 07/21/2024] [Indexed: 07/27/2024]
Abstract
Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown. This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes. Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11-18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11-22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24-5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05). Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke.
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Affiliation(s)
- Honglian Duan
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China
| | - Yuchuan Ding
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
| | - Zhe Cheng
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China
| | - Lipeng Cai
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China
| | - Yanna Tong
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China
| | - Fengli Che
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China
| | - Zhenzhen Han
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China
| | - Fengwu Li
- Luhe Institute of Neuroscience, Capital Medical University, Beijing, China
| | - Qingzhu Wang
- Luhe Institute of Neuroscience, Capital Medical University, Beijing, China
| | - Xiaokun Geng
- Department of Neurology and the Stroke Intervention & Translational Center (SITC), Beijing Luhe Hospital, Capital Medical University, China; Luhe Institute of Neuroscience, Capital Medical University, Beijing, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
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Alshuweishi Y, Alfayez D, Almufarrih AA, Abudawood A, Alyami H, Alshuweishi FA, Al-Sheikh YA, Alfhili MA. Elevated Alanine Transaminase-to-Platelet Index (APRI) Is Associated with Obesity and Distinct Forms of Dyslipidemia: A Retrospective Cross-Sectional Study. J Clin Med 2024; 13:5650. [PMID: 39337137 PMCID: PMC11432626 DOI: 10.3390/jcm13185650] [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: 07/08/2024] [Revised: 09/17/2024] [Accepted: 09/22/2024] [Indexed: 09/30/2024] Open
Abstract
Background: Obesity is a pathological condition and a major risk factor for dyslipidemia, type 2 diabetes, and non-alcoholic fatty liver disease. Recent research highlighted the association of non-invasive serum markers with these conditions but the clinical utility of ALT APRI in obesity and its relationship with dyslipidemia remain unexplored. Methods: We examined the association of ALT APRI in 165 non-diabetic adults stratified by BMI and serum lipid parameters. Results: Obese subjects had significantly higher APRI than lean subjects, with an area under the curve (AUC) of 0.65 (p = 0.019). Medians of APRI were significantly increased in subjects with high TG, TG/HDL, TC/HDL, and LDL/HDL and low HDL. Notably, all lipid parameters and ratios were significantly elevated in the highest APRI tertile, compared with patients in the lowest tertile. APRI was weakly yet significantly correlated with BMI (R2 = 0.032, p = 0.022), HDL (R2 = 0.071), TG/HDL (R2 = 0.031), TC/HDL (R2 = 0.063), LDL/HDL (R2 = 0.072), and TyG index (R2 = 0.081). While APRI only showed a discriminating capacity for HDL (AUC: 0.69, p = 0.003), TG/HDL (AUC: 0.63, p = 0.020), LDL/HDL (AUC: 0.68, p < 0.001), and TyG index (AUC: 0.65, p = 0.037), the highest diagnostic performance of APRI was observed with TC/HDL (AUC: 0.74, p < 0.001). Additionally, APRI was a risk factor for high TG (OR: 1.6, p = 0.028), low HDL (OR: 2.7, p = 0.0002), high TG/HDL (OR: 1.94, p = 0.0011), high TC/HDL (OR: 2.3, p < 0.0001), high LDL/HDL (OR: 2.2, p = 0.0001), and high TyG index (OR: 2.1, p = 0.008). Conclusions: Our findings argue for the role of APRI as a potential marker for obesity and dyslipidemia, which requires further confirmation in longitudinal studies.
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Affiliation(s)
- Yazeed Alshuweishi
- Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia
| | - Dalal Alfayez
- Department of Family and Community Medicine, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Abdulmalik A Almufarrih
- Department of Family and Community Medicine, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Arwa Abudawood
- Department of Family and Community Medicine, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
| | - Hanan Alyami
- Department of Medical and Surgical Nursing, College of Nursing, Princess Norah bint Abdurrahman University, Riyadh 11564, Saudi Arabia
| | - Faisal A Alshuweishi
- Department of Pathology and Laboratory Medicine, King Khalid University Hospital, King Saud University Medical City, Riyadh 12372, Saudi Arabia
| | - Yazeed A Al-Sheikh
- Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia
| | - Mohammad A Alfhili
- Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 12372, Saudi Arabia
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Ramírez-Vélez R, Izquierdo M, García-Hermoso A, Correa-Rodríguez M. Reference values and associated factors of controlled attenuation parameter and liver stiffness in adults: A cross-sectional study. Nutr Metab Cardiovasc Dis 2024; 34:1879-1889. [PMID: 38866615 DOI: 10.1016/j.numecd.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 04/02/2024] [Accepted: 04/08/2024] [Indexed: 06/14/2024]
Abstract
BACKGROUND & AIMS The utilization of non-invasive techniques for liver fibrosis and steatosis assessment has gained acceptance as a viable substitute for liver biopsy in clinical practice. This study aimed to establish normative data for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by age and gender, as well as to explore the relationship between anthropometric measures, clinical status, and biochemical profile according to the 90th percentile cut-off values for CAP/LSM in a U.S. adult population. METHODS AND RESULTS In this cross-sectional analysis, 7.522 US adults aged 20-80 years from the National Health and Nutrition Examination Survey (NHANES 2017-2020) were included. CAP and LSM were quantified using the FibroScan® 502-v2 device. A comprehensive range of data was collected, including sociodemographic, anthropometric, biochemical, lifestyle, and clinical conditions. Participants were segmented by sex and age. The median ± standard deviation (SD) for CAP was significantly lower in women (258.27 ± 61.02 dB/m) than in men (273.43 ± 63.56 dB/m), as was the median ± SD for LSM (women: 5.50 ± 4.12 kPa, men: 6.36 ± 5.63 kPa). Although median CAP and LSM values displayed an upward trend with age, statistical significance was not achieved. Notably, higher liver CAP values (above the 90th percentile) correlated with more pronounced clinical and biochemical profile differences compared to lower CAP values (below the 90th percentile) (p < 0.001). CONCLUSIONS Our study provides age- and sex-stratified standard values for CAP and LSM in a sizeable, nationally representative cohort of adults. The evidence of sex-specific variations in TE test results from our study sets the stage for future research to further corroborate these findings.
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Affiliation(s)
- Robinson Ramírez-Vélez
- Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain; CIBER of Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Mikel Izquierdo
- Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain; CIBER of Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Antonio García-Hermoso
- Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
| | - María Correa-Rodríguez
- Department of Nursing, Faculty of Health Sciences, University of Granada (UGR), Av. Ilustración, 60, 18016 Granada, Spain; Instituto de Investigación Biosanitaria Granada (IBIS Granada), Av. de Madrid, 15, Pabellón de consultas externas 2, 2(a) planta, 18012 Granada, Spain.
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7
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Mumtaz T, Tariq K, Kanwal K, Tariq Z. A case-control regression analysis of liver enzymes in obesity-induced metabolic disorders in South Asian females. PLoS One 2024; 19:e0303835. [PMID: 39024244 PMCID: PMC11257360 DOI: 10.1371/journal.pone.0303835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 05/02/2024] [Indexed: 07/20/2024] Open
Abstract
Excessive body weight may disrupt hepatic enzymes that may be aggravated by obesity-related comorbidities. The current case-control study was designed to evaluate the extent of liver enzyme alteration in obesity-related metabolic disorders. Obese females with BMI ≥ 30 suffering from metabolic disorders were grouped according to existing co-morbidity and their hepatic enzymes were compared with non-obese healthy females. The resultant data was subjected to analysis of variance and mean difference in liver enzymes were calculated at P = 0.05. Analysis of variance indicated that obese diabetic and obese hypertensive females had almost 96% and 67% increase in the concentration of gamma-glutamyl transferase than control, respectively (P<0.0001). The obese females suffering from diabetes and hypertension exhibited nearly 54% enhancement in alanine transaminase level (P<0.0001) and a 17% increase in aspartate aminotransferase concentration (P = 0.0028). Obesity along with infertility decline liver enzyme production and a 31% significant decline in aspartate aminotransferase was observed while other enzyme concentrations were not significantly altered. Regression analysis was performed on the resultant data to understand the association between liver enzyme alteration and the development of metabolic diseases. Regression analysis indicated that obese diabetic and obese diabetic hypertensive women had 20% production of normal liver enzymes and 80% enzymes produced abnormally. Obese hypertensive and obese infertile females had only 5% and 6% normal production of liver enzymes, respectively. This research leads to the conclusion that the ability of the liver to function normally is reduced in obesity-related diabetes and hypertension. This may be due to inflamed and injured liver and poses a serious threat to developing fatty liver disease and ultimately liver cirrhosis.
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Affiliation(s)
- Tamseela Mumtaz
- Department of Zoology, Government College Women University Faisalabad, Punjab, Pakistan
| | - Kainat Tariq
- Department of Zoology, Government College Women University Faisalabad, Punjab, Pakistan
| | - Khadija Kanwal
- Department of Statistics, Government College Women University Faisalabad, Punjab, Pakistan
| | - Zainab Tariq
- Department of Zoology, Government College Women University Faisalabad, Punjab, Pakistan
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8
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Jiménez-Cortegana C, López-Enríquez S, Alba G, Santa-María C, Martín-Núñez GM, Moreno-Ruiz FJ, Valdés S, García-Serrano S, Rodríguez-Díaz C, Ho-Plágaro A, Fontalba-Romero MI, García-Fuentes E, Garrido-Sánchez L, Sánchez-Margalet V. The Expression of Genes Related to Reverse Cholesterol Transport and Leptin Receptor Pathways in Peripheral Blood Mononuclear Cells Are Decreased in Morbid Obesity and Related to Liver Function. Int J Mol Sci 2024; 25:7549. [PMID: 39062791 PMCID: PMC11276733 DOI: 10.3390/ijms25147549] [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: 05/27/2024] [Revised: 07/02/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.
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MESH Headings
- Humans
- Obesity, Morbid/metabolism
- Obesity, Morbid/surgery
- Obesity, Morbid/genetics
- Male
- Leukocytes, Mononuclear/metabolism
- Female
- Receptors, Leptin/genetics
- Receptors, Leptin/metabolism
- Adult
- Cholesterol/metabolism
- Liver X Receptors/metabolism
- Liver X Receptors/genetics
- ATP Binding Cassette Transporter 1/genetics
- ATP Binding Cassette Transporter 1/metabolism
- Middle Aged
- Liver/metabolism
- ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism
- ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics
- Signal Transduction
- Biological Transport
- Gene Expression Regulation
- Non-alcoholic Fatty Liver Disease/metabolism
- Non-alcoholic Fatty Liver Disease/genetics
- Adaptor Proteins, Signal Transducing/metabolism
- Adaptor Proteins, Signal Transducing/genetics
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Grants
- PI09/01016 Instituto de Salud Carlos III
- PE-0098-2019 Consejería de Salud y Familias, Junta de Andalucía, Spain
- PI-2013-575 Consejería de Salud y Familias, Junta de Andalucía, Spain
- P10-CTS6928, P11-CTS8161, P11-CTS8081, CTS-151 Consejería de Universidad, Investigación e Innovación, Junta de Andalucia, Spain
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Affiliation(s)
- Carlos Jiménez-Cortegana
- Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, 41009 Seville, Spain; (C.J.-C.); (S.L.-E.); (G.A.); (V.S.-M.)
| | - Soledad López-Enríquez
- Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, 41009 Seville, Spain; (C.J.-C.); (S.L.-E.); (G.A.); (V.S.-M.)
| | - Gonzalo Alba
- Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, 41009 Seville, Spain; (C.J.-C.); (S.L.-E.); (G.A.); (V.S.-M.)
| | - Consuelo Santa-María
- Department of Biochemistry and Molecular Biology, University of Seville Pharmacy School, 41012 Seville, Spain;
| | - Gracia M. Martín-Núñez
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (G.M.M.-N.); (L.G.-S.)
| | - Francisco J. Moreno-Ruiz
- Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain;
| | - Sergio Valdés
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (S.V.); (S.G.-S.); (M.I.F.-R.)
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 29010 Málaga, Spain
| | - Sara García-Serrano
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (S.V.); (S.G.-S.); (M.I.F.-R.)
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 29010 Málaga, Spain
| | - Cristina Rodríguez-Díaz
- Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (C.R.-D.); (A.H.-P.)
| | - Ailec Ho-Plágaro
- Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (C.R.-D.); (A.H.-P.)
| | - María I. Fontalba-Romero
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (S.V.); (S.G.-S.); (M.I.F.-R.)
| | - Eduardo García-Fuentes
- Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (C.R.-D.); (A.H.-P.)
- CIBER Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, 29010 Málaga, Spain
- Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain
| | - Lourdes Garrido-Sánchez
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain; (G.M.M.-N.); (L.G.-S.)
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 29010 Málaga, Spain
| | - Víctor Sánchez-Margalet
- Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, 41009 Seville, Spain; (C.J.-C.); (S.L.-E.); (G.A.); (V.S.-M.)
- Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/Virgen Macarena, CSIC, Universidad de Sevilla, 41013 Seville, Spain
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9
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Wang D, Zhou BY, Xiang L, Chen XY, Feng JX. Alanine aminotransferase as a risk marker for new-onset metabolic dysfunction-associated fatty liver disease. World J Gastroenterol 2024; 30:3132-3139. [PMID: 39006380 PMCID: PMC11238669 DOI: 10.3748/wjg.v30.i25.3132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/07/2024] [Accepted: 06/13/2024] [Indexed: 07/01/2024] Open
Abstract
In this editorial, we comment on the article by Chen et al. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.
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Affiliation(s)
- Di Wang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Bing-Yan Zhou
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Lei Xiang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xu-Yong Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jie-Xiong Feng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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10
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Talari NK, Mattam U, Kaminska D, Sotomayor-Rodriguez I, Rahman AP, Péterfy M, Pajukanta P, Pihlajamäki J, Chella Krishnan K. Hepatokine ITIH3 protects against hepatic steatosis by downregulating mitochondrial bioenergetics and de novo lipogenesis. iScience 2024; 27:109709. [PMID: 38689636 PMCID: PMC11059128 DOI: 10.1016/j.isci.2024.109709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 02/16/2024] [Accepted: 04/06/2024] [Indexed: 05/02/2024] Open
Abstract
Recent studies demonstrate that liver secretory proteins, also known as hepatokines, regulate normal development, obesity, and simple steatosis to non-alcoholic steatohepatitis (NASH) progression. Using a panel of ∼100 diverse inbred strains of mice and a cohort of bariatric surgery patients, we found that one such hepatokine, inter-trypsin inhibitor heavy chain 3 (ITIH3), was progressively lower in severe non-alcoholic fatty liver disease (NAFLD) disease states highlighting an inverse relationship between Itih3/ITIH3 expression and NAFLD severity. Follow-up animal and cell culture models demonstrated that hepatic ITIH3 overexpression lowered liver triglyceride and lipid droplet accumulation, respectively. Conversely, ITIH3 knockdown in mice increased the liver triglyceride in two independent NAFLD models. Mechanistically, ITIH3 reduced mitochondrial respiration and this, in turn, reduced liver triglycerides, via downregulated de novo lipogenesis. This was accompanied by increased STAT1 signaling and Stat3 expression, both of which are known to protect against NAFLD/NASH. Our findings indicate hepatokine ITIH3 as a potential biomarker and/or treatment for NAFLD.
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Affiliation(s)
- Noble Kumar Talari
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Ushodaya Mattam
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Dorota Kaminska
- Department of Medicine, Division of Cardiology, University of California Los Angeles, Los Angeles, CA, USA
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Irene Sotomayor-Rodriguez
- Medical Sciences Baccalaureate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Afra P. Rahman
- Medical Sciences Baccalaureate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Miklós Péterfy
- Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA, USA
| | - Päivi Pajukanta
- Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA
- Institute for Precision Health, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, USA
| | - Jussi Pihlajamäki
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
- Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
| | - Karthickeyan Chella Krishnan
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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11
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Lee J, Li Y, Cheng JT, Liu IM, Cheng KC. Development of Syringaldehyde as an Agonist of the GLP-1 Receptor to Alleviate Diabetic Disorders in Animal Models. Pharmaceuticals (Basel) 2024; 17:538. [PMID: 38675498 PMCID: PMC11054907 DOI: 10.3390/ph17040538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 04/28/2024] Open
Abstract
The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future.
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Affiliation(s)
- Jenpei Lee
- Department of Neurosurgery, Da Chien General Hospital, Miaoli City 36052, Taiwan;
| | - Yingxiao Li
- Department of Nursing, Tzu Chi University of Science and Technology, Hualien City 970302, Taiwan;
| | - Juei-Tang Cheng
- Graduate Institute of Medical Science, Chang Jung Christian University, Tainan City 71101, Taiwan
| | - I-Min Liu
- Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan;
| | - Kai-Chun Cheng
- Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan;
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12
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Jiang R, Zhou Y, Han L, Hong Z. Serum vitamin D is associated with ultrasound-defined hepatic fibrosis. Clin Res Hepatol Gastroenterol 2023; 47:102228. [PMID: 37865224 DOI: 10.1016/j.clinre.2023.102228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/18/2023] [Indexed: 10/23/2023]
Abstract
BACKGROUND Evidences from population-based investigations on the exact relationship between vitamin D and the severity of liver fibrosis remain debated and conflicting. Here, we aim to explore the relationship between serum vitamin D and ultrasound-defined advanced hepatic fibrosis in the US participants with nonalcoholic fatty liver disease (NAFLD). METHODS In the retrospective study, individuals with intact information on interesting variables from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were included. NAFLD was diagnosed on the basis of controlling attenuation parameter (CAP) value≥ 274 dB/m without causes of other chronic hepatic diseases. We identified advanced fibrosis grades (F2) by liver stiffness measurement (LSM) score of ≥ 8.2 kPa in NAFLD patients. The impact of elevated serum vitamin D on the prevalence of hepatic fibrosis was assessed by multivariate logistic regression models on the basis of the NHANES recommended weights. RESULTS The study involved 1624 subjects with NAFLD in total, and 305 (18.28 %, weighted%) of whom were diagnosed with advanced hepatic fibrosis according to the definition based on parameters obtained from vibration controlled transient elastography (VCTE). In the multivariate logistic regression analysis, serum vitamin D presented a negative relationship to hepatic fibrosis with lower odds in patients with hepatic steatosis after being adjusted for potential confounding factors (fully adjusted: OR=0.47, 95 % CI: 0.24-0.90, p = 0.034). Our subgroup analysis revealed that the inverse relationship was still existed in males (fully adjusted: OR = 0.34, 95 % CI: 0.17-0.70, p = 0.014), non-obese subjects (fully adjusted: OR = 0.20, 95 % CI: 0.04-0.89, p = 0.042) and participants below 60 years (fully adjusted: OR = 0.43, 95 % CI: 0.21-0.90, p = 0.033), whereas in models adjusted for the potential confounding factors, no statistically significant correlation was noted in females, obese subjects or subjects with age≥ 60 years. CONCLUSIONS This large population-based investigation indicated that elevated serum vitamin D reduced the onset of advanced fibrosis diagnosed by ultrasound in males, non-obese subjects and younger participants with NAFLD.
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Affiliation(s)
- Rong Jiang
- Jiangsu Health Vocational College, Nanjing, Jiangsu 210000, China.
| | - Yichao Zhou
- Department of Occupation Disease Prevention and Cure, Changzhou Wujin District Center for Disease Control and Prevention, Changzhou, Jiangsu 213100, China
| | - Lei Han
- Department of Occupation Disease Prevention and Cure, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210000, China.
| | - Zhen Hong
- Jiangsu Health Vocational College, Nanjing, Jiangsu 210000, China.
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13
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Tilg H, Adolph TE, Tacke F. Therapeutic modulation of the liver immune microenvironment. Hepatology 2023; 78:1581-1601. [PMID: 37057876 DOI: 10.1097/hep.0000000000000386] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 03/14/2023] [Indexed: 04/15/2023]
Abstract
Inflammation is a hallmark of progressive liver diseases such as chronic viral or immune-mediated hepatitis, alcohol-associated liver disease, and NAFLD. Preclinical and clinical studies have provided robust evidence that cytokines and related cellular stress sensors in innate and adaptive immunity orchestrate hepatic disease processes. Unresolved inflammation and liver injury result in hepatic scarring, fibrosis, and cirrhosis, which may culminate in HCC. Liver diseases are accompanied by gut dysbiosis and a bloom of pathobionts, fueling hepatic inflammation. Anti-inflammatory strategies are extensively used to treat human immune-mediated conditions beyond the liver, while evidence for immunomodulatory therapies and cell therapy-based strategies in liver diseases is only emerging. The development and establishment of novel immunomodulatory therapies for chronic liver diseases has been dampened by several clinical challenges, such as invasive monitoring of therapeutic efficacy with liver biopsy in clinical trials and risk of DILI in several studies. Such aspects prevented advancements of novel medical therapies for chronic inflammatory liver diseases. New concepts modulating the liver immune environment are studied and eagerly awaited to improve the management of chronic liver diseases in the future.
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Affiliation(s)
- Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany
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14
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Khalid S, Arshad M, Raza K, Mahmood S, Siddique F, Aziz N, Khan S, Khalid W, AL‐Farga A, Aqlan F. Assessment of hepatoprotective, nephroprotective efficacy, and antioxidative potential of Moringa oleifera leaf powder and ethanolic extract against PCOS-induced female albino mice ( Mus Musculus). Food Sci Nutr 2023; 11:7206-7217. [PMID: 37970416 PMCID: PMC10630814 DOI: 10.1002/fsn3.3646] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/03/2023] [Accepted: 08/13/2023] [Indexed: 11/17/2023] Open
Abstract
Moringa oleifera is a medicinal plant that has anti-inflammatory, antihypertensive, antidiabetic, tissue-protective, and antioxidant activities. Here, we evaluated the protective effect of M. oleifera leaf powder (MoLP) and 70% ethanol M. oleifera leaf extract (MoLE) on mitigating polycystic ovary syndrome (PCOS)-induced liver and kidney dysfunction via regulating oxidative stress in female albino mice (Mus musculus). The efficacy of M. oleifera was compared with metformin (standard medicine used to treat infertility in women). PCOS was induced by intramuscular injection of testosterone enanthate at 1.0 mg/100 g BW for 35 days. PCOS-induced mice were treated with MoLP (250 and 500 mg/Kg), MoLE (250 and 500 mg/kg), and metformin (250 mg/kg) orally for 14 days. Renal function test (RFT), liver function test (LFT), and oxidative stress biomarker malondialdehyde (MDA) were quantified in serum at 0, 7, and 14 days of intervention. Mice treated with M. oleifera and metformin showed a significant decrease (p < .001) in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (ALP), total bilirubin, urea, creatinine, and a significant increase (p < .001) in total protein, albumin, globulin, and albumin/globulin (A/G) ratio. Oxidative stress decreased significantly (p = .00) with respect to treatments, exposure days, and their interaction in metformin and all M. oleifera-treated groups. M. oleifera leaf powder and extract reduce oxidative stress and enhance nephron-hepatic activity in PCOS-induced female albino mice.
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Affiliation(s)
| | | | - Komal Raza
- Liver CenterDistrict Headquarter HospitalFaisalabadPakistan
| | - Shahid Mahmood
- Institute of Food Science and NutritionUniversity of SargodhaSargodhaPakistan
| | - Farzana Siddique
- Institute of Food Science and NutritionUniversity of SargodhaSargodhaPakistan
| | - Nida Aziz
- Department of ZoologyUniversity of SargodhaSargodhaPakistan
| | - Sarfraz Khan
- Department of ChemistryAir Base CollegeSargodhaPakistan
| | - Waseem Khalid
- University Institute of Food Science and TechnologyThe University of LahoreLahorePakistan
| | - Ammar AL‐Farga
- Department of Biochemistry, College of SciencesUniversity of JeddahJeddahSaudi Arabia
| | - Faisal Aqlan
- Department of Chemistry, College of SciencesIbb UniversityIbbYemen
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15
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Xing Y, Zhang P, Li X, Jin S, Xu M, Jia J, Wang HJ, Li L, Wang H. New predictive models and indices for screening MAFLD in school-aged overweight/obese children. Eur J Pediatr 2023; 182:5025-5036. [PMID: 37648793 DOI: 10.1007/s00431-023-05175-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 08/20/2023] [Accepted: 08/22/2023] [Indexed: 09/01/2023]
Abstract
Currently, most predictions of metabolic-associated fatty liver disease (MAFLD) in school-aged children utilize indicators that usually predict nonalcoholic fatty liver disease (NAFLD). The present study aimed to develop new predictive models and predictors for children with MAFLD, which could enhance the feasibility of MAFLD screening programs in the future. A total of 331 school-aged overweight/obese children were recruited from six primary schools in Ningbo city, China. Hepatic steatosis and fibrosis were detected with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Machine learning methods were adapted to build a set of variables to predict MAFLD in children. Then, the area under the curve (AUC) of multiple models and indices was compared to predict pediatric MAFLD. Compared with non-MAFLD children, children with MAFLD had more obvious metabolic disturbances, as they had higher anthropometric indicators, alanine aminotransferase, fasting plasma glucose, and inflammation indicators (white blood cell count, hemoglobin, neutrophil count) (all P < 0.05). The optimal variables for all subjects selected by random forest (RF) were alanine aminotransferase, uric acid, insulin, and BMI. The logistic regression (LR) model performed best, with AUC values of 0.758 for males and 0.642 for females in predicting MAFLD. LnAI-BMI, LnAI, and LnAL-WHtR were approving indices for predicting pediatric MAFLD in all participants, boys and girls individually. CONCLUSIONS This study developed LR models and sex-specific indices for predicting MAFLD in overweight/obese children that may be useful for widespread screening and identification of children at high risk of MAFLD for early treatment. WHAT IS KNOWN • Most of the indicators predicting pediatric MAFLD are derived from the predictive indicators for NAFLD, but the diagnostic criteria for MAFLD and NAFLD are not exactly the same. • The accuracy of predictors based on routine physical examination and blood biochemical indicators to diagnose MAFLD is limited. WHAT IS NEW • This study developed indicators based on routine examination parameters that have approving performance for MAFLD, with AUC values exceeding 0.70.
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Affiliation(s)
- Yunfei Xing
- Department of Maternal and Child Health, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - PingPing Zhang
- Ningbo Center for Healthy Lifestyle Research, Ningbo City First Hospital, Ningbo, Zhejiang Province, 315000, China
| | - Xueying Li
- Department of Maternal and Child Health, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Shifeng Jin
- Department of Maternal and Child Health, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Miao Xu
- Department of Endocrinology and Metabolism, Ningbo First Hospital, No. 59 Liuting Street, Haishu District, Ningbo, Zhejiang Province, 315000, China
| | - Jinzhu Jia
- Department of Biostatistics, School of Public Health, Peking University, Beijing, 100191, China
| | - Hai-Jun Wang
- Department of Maternal and Child Health, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Li Li
- Department of Endocrinology and Metabolism, Ningbo First Hospital, No. 59 Liuting Street, Haishu District, Ningbo, Zhejiang Province, 315000, China.
| | - Hui Wang
- Department of Maternal and Child Health, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
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16
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Nederveen JP, Mastrolonardo AJ, Xhuti D, Di Carlo A, Manta K, Fuda MR, Tarnopolsky MA. Novel Multi-Ingredient Supplement Facilitates Weight Loss and Improves Body Composition in Overweight and Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients 2023; 15:3693. [PMID: 37686725 PMCID: PMC10490028 DOI: 10.3390/nu15173693] [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: 06/01/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND Despite the growing recognition of the obesity crisis, its rates continue to rise. The current first-line therapies, such as dietary changes, energy restriction, and physical activity, are typically met with poor adherence. Novel nutritional interventions can address the root causes of obesity, including mitochondrial dysfunction, and facilitate weight loss. OBJECTIVE The objective of this study was to investigate the effects of a multi-ingredient nutritional supplement designed to facilitate mitochondrial function and metabolic health outcomes over a 12 wk period. METHODS Fifty-five overweight and/or obese participants (age (mean ± SEM): 26 ± 1; body mass index (BMI) (kg/m2): 30.5 ± 0.6) completed this double-blind, placebo-controlled clinical trial. Participants were randomized to 12 wks of daily consumption of multi-ingredient supplement (MIS; n = 28; containing 50 mg forskolin, 500 mg green coffee bean extract, 500 mg green tea extract, 500 mg beet root extract, 400 mg α-lipoic acid, 200 IU vitamin E, and 200 mg CoQ10) or control placebo (PLA, n = 27; containing microcrystalline cellulose) matched in appearance. The co-primary outcomes were bodyweight and fat mass (kg) changes. The secondary outcomes included other body composition measures, plasma markers of obesity, fatty liver disease biomarkers, resting energy metabolism, blood pressure, physical performance, and quality of life. The post-intervention differences between MIS and PLA were examined via ANCOVA which was adjusted for the respective pre-intervention variables. RESULTS After adjustment for pre-intervention data, there was a significant difference in weight (p < 0.001) and fat mass (p < 0.001) post-intervention between the PLA and MIS treatment arms. Post-intervention weight and fat mass were significantly lower in MIS. Significant post-intervention differences corrected for baseline were found in markers of clinical biochemistry (AST, p = 0.017; ALT, p = 0.008), molecular metabolism (GDF15, p = 0.028), and extracellular vesicle-associated miRNA species miR-122 and miR-34a in MIS (p < 0.05). CONCLUSIONS Following the 12 wks of MIS supplementation, weight and body composition significantly improved, concomitant with improvements in molecular markers of liver health and metabolism.
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Affiliation(s)
- Joshua P. Nederveen
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
| | - Alexander J. Mastrolonardo
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
| | - Donald Xhuti
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
| | - Alessia Di Carlo
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
| | - Katherine Manta
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
| | - Matthew R. Fuda
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
| | - Mark A. Tarnopolsky
- Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada; (J.P.N.)
- Exerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, Canada
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17
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Zhao B, Liu Y, Yang Y, He J. Association of Systemic Immune-Inflammation Index with Non-Alcoholic Fatty Liver Disease: A Population-Based Cross-Sectional Study. Risk Manag Healthc Policy 2023; 16:1581-1592. [PMID: 37605743 PMCID: PMC10440121 DOI: 10.2147/rmhp.s419183] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 07/18/2023] [Indexed: 08/23/2023] Open
Abstract
Background The aim of this study was to explore the relationship between systemic immune-inflammation (SII) index with non-alcoholic fatty liver disease (NAFLD) in the general population of the United States (U.S.). Methods We conducted a cross-sectional study of subjects in the National Health and Nutrition Examination Survey 2017-2018. For the analysis of the association between SII index and risk of NAFLD, the restricted cubic spline (RCS) plot, we performed multivariable logistic regression models and subgroup analysis. In addition, generalized additive models with smooth functions were conducted for the relationship between the SII index and the ZJU index, the BARD score, and the NAFLD fibrosis score. Results There were a total of 1197 individuals in our study. Taking into account known confounding variables, compared with the lowest quartiles, the odds ratios with 95% confidence intervals for NAFLD across the quartiles were 0.923 (0.585, 1.455), 0.563 (0.351, 0.901), and 1.061 (0.669, 1.682), respectively. As shown by the RCS plot, the SII index was linked with NAFLD risk in a U-shaped pattern. Based on the results of subgroup analysis, SII index and NAFLD risk were U-curve correlated among participants in all age groups, male or female, with or without hypertension, with diabetes mellitus, and with a BMI of <30 or >30 kg/m2. The SII index was linearly positive with the ZJU index but negative with the NAFLD fibrosis score. However, the SII index and BARD score showed a trend of first decreasing, then increasing, and then decreasing. Conclusion The U-shaped relationships exist between SII index and risk of NAFLD, which highlighted that we should focus on the dynamic change of SII index.
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Affiliation(s)
- Bi Zhao
- Department of Gastroenterology, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, 201500, People’s Republic of China
| | - Yuee Liu
- Department of Emergency, Changhai Hospital, Shanghai, 200433, People’s Republic of China
| | - Yi Yang
- Department of Emergency, Ruijin Hospital and Luwan Branch, School of Medicine, Shanghai Jiaotong University, Shanghai, 200020, People’s Republic of China
| | - Jihui He
- Department of Gastroenterology, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, 201500, People’s Republic of China
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18
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Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 2023; 77:1797-1835. [PMID: 36727674 PMCID: PMC10735173 DOI: 10.1097/hep.0000000000000323] [Citation(s) in RCA: 924] [Impact Index Per Article: 462.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 01/18/2023] [Indexed: 02/03/2023]
Affiliation(s)
- Mary E. Rinella
- University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA
| | | | | | | | - Stephen Caldwell
- School of Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - Diana Barb
- University of Florida College of Medicine, Gainesville, Florida, USA
| | | | - Rohit Loomba
- University of California, San Diego, San Diego, California, USA
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19
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Yang T, Wang J, Wu L, Guo F, Huang F, Song Y, Jing N, Pan M, Ding X, Cao Z, Liu S, Qin G, Zhao Y. Development and validation of a nomogram to estimate future risk of type 2 diabetes mellitus in adults with metabolic syndrome: prospective cohort study. Endocrine 2023; 80:336-345. [PMID: 36940011 DOI: 10.1007/s12020-023-03329-3] [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: 10/03/2022] [Accepted: 02/10/2023] [Indexed: 03/21/2023]
Abstract
OBJECTIVES To develop and validate the 4-year risk of type 2 diabetes mellitus among adults with metabolic syndrome. DESIGN Retrospective cohort study of a large multicenter cohort with broad validation. SETTINGS The derivation cohort was from 32 sites in China and the geographic validation cohort was from Henan population-based cohort study. RESULTS 568 (17.63) and 53 (18.67%) participants diagnosed diabetes during 4-year follow-up in the developing and validation cohort, separately. Age, gender, body mass index, diastolic blood pressure, fasting plasma glucose and alanine aminotransferase were included in the final model. The area under curve for the training and external validation cohort was 0.824 (95% CI, 0.759-0.889) and 0.732 (95% CI, 0.594-0.871), respectively. Both the internal and external validation have good calibration plot. A nomogram was constructed to predict the probability of diabetes during 4-year follow-up, and on online calculator is also available for a more convenient usage ( https://lucky0708.shinyapps.io/dynnomapp/ ). CONCLUSION We developed a simple diagnostic model to predict 4-year risk of type 2 diabetes mellitus among adults with metabolic syndrome, which is also available as web-based tools ( https://lucky0708.shinyapps.io/dynnomapp/ ).
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Affiliation(s)
- Tongyue Yang
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Jiao Wang
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Lina Wu
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Feng Guo
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Fengjuan Huang
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Yi Song
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Na Jing
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Mengxing Pan
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Xiaoxu Ding
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Zhe Cao
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Shiyu Liu
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Guijun Qin
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Yanyan Zhao
- Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
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20
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Bortz JH. Metabolic-Associated Fatty Liver Disease: Opportunistic Screening at CT Colonography. CT COLONOGRAPHY FOR RADIOGRAPHERS 2023:277-290. [DOI: 10.1007/978-3-031-30866-6_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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21
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Bjørnå ER, Engelsen MT, El-Serag HB, Ness-Jensen E. Prevalence and risk factors of nonalcoholic fatty liver disease in a general population, the HUNT study. Scand J Gastroenterol 2022; 58:505-511. [PMID: 36314512 DOI: 10.1080/00365521.2022.2139633] [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: 11/06/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the metabolic syndrome is the main risk factor. Alanine aminotransferase (ALT) is widely used to screen for NAFLD, and the aims of this study were to assess the prevalence and risk factors of NAFLD in a general population. METHODS The study was based on the third population-based Trøndelag Health Study (HUNT3), Norway, performed 2006-2008. In HUNT3, ALT and lipids were analyzed, anthropometric measures done, and comorbidity and risk factors reported. Elevated ALT was used to define NAFLD and participants with other diagnosed liver diseases and excessive alcohol consumption were excluded. Multivariable logistic regression reporting odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors. RESULTS In HUNT3, 2373 (4.7%) of 50,006 participants were diagnosed with NAFLD. The risk increased with obesity (OR 1.73, 95% CI 1.46-2.05) and very increased waist circumference (OR 1.97, 95% CI 1.65-2.35), and the risk increased dose-dependently (p for trend <0.001). Hypertension (OR 1.58, 95% CI 1.42-1.76), diabetes mellitus (OR 1.48, 95% CI 1.30-1.68), high triglycerides (OR 1.55, 95% CI 1.41-1.71), high total cholesterol (OR 1.52, 95% CI 1.29-1.81) and low high-density lipoproteins (OR 1.33, 95% CI 1.21-1.47) also increased the risk of NAFLD. The risk was lower in men (OR 0.71, 95% CI 0.64-0.79) and among current smokers (OR 0.79, 95% CI 0.70-0.89). CONCLUSION NAFLD is a common condition in the general population. NAFLD should be suspected in individuals with abdominal obesity, hypertension, diabetes mellitus and dyslipidemias.
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Affiliation(s)
- Erika R Bjørnå
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
| | - Martine T Engelsen
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
| | - Hashem B El-Serag
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Eivind Ness-Jensen
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.,Medical Department, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.,Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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22
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Diagnosis of drug-induced liver injury in model mice by studying the inhibitory effect of serum components on P450 inhibition assay. Chem Biol Interact 2022; 365:110075. [DOI: 10.1016/j.cbi.2022.110075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 07/15/2022] [Accepted: 07/24/2022] [Indexed: 11/20/2022]
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23
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Ahn JS, Cho S, Park WJ. Changes in the Health Indicators of Hospital Medical Residents During the Four-Year Training Period in Korea. J Korean Med Sci 2022; 37:e202. [PMID: 35762145 PMCID: PMC9239842 DOI: 10.3346/jkms.2022.37.e202] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 05/23/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND In South Korea, the legal maximum working hours per week for medical residents is 88 hours, which are longer than those for other occupations, and the intensity of the workload is also remarkably high. Long working hours and job-related stress can worsen the health status of residents. This study aimed to analyze the four-year annual health checkup (AHC) data of residents to identify changes in their health indicators. METHODS This study included 457 male residents who received 4 years of training at a university hospital. They underwent an AHC every year during the training period. Changes in health indicators and related factors over the 4 years were investigated. RESULTS Body mass indices (BMI), blood pressures (BPs), liver function test (LFT) results, and total cholesterol (TC) levels were significantly worsened during the training period. The increases were the highest in the early training years, between the 2nd and 1st AHC. The working hours of the fourth-year residents were the shortest and showed low smoking and drinking rates and high regular exercise rates. On comparing by department, surgical residents showed the highest increases in BMI, diastolic BP, and fasting blood glucose (FBG), LFT enzyme, and TC levels during the training period, compared to residents from the medical and clinical support departments. Residents who were working ≥ 80 hours showed significantly higher FBG and LFT enzyme levels than those working < 80 hours. CONCLUSION This study is meaningful as it is the first study in Korea to investigate the changes in the health of residents through objective health indicators. The possibility of the 4-year training period adversely affecting the health of residents was confirmed. Health indicators were significantly worsened, especially in the early training period, in surgical residents, and in residents who worked for long hours. Efforts are needed to restrict long working hours and distribute workload during the 4-year training period.
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Affiliation(s)
- Ji-Sung Ahn
- Department of Occupational and Environmental Medicine, Mokpo Hankook Hospital, Mokpo, Korea
| | - Seunghyeon Cho
- Department of Occupational and Environmental Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Won-Ju Park
- Department of Occupational and Environmental Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.
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24
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Liu J, Ayada I, Zhang X, Wang L, Li Y, Wen T, Ma Z, Bruno MJ, de Knegt RJ, Cao W, Peppelenbosch MP, Ghanbari M, Li Z, Pan Q. Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults. Clin Gastroenterol Hepatol 2022; 20:e573-e582. [PMID: 33618024 DOI: 10.1016/j.cgh.2021.02.030] [Citation(s) in RCA: 111] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 02/10/2021] [Accepted: 02/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). In this study, we aim to estimate the global prevalence of MAFLD specifically in overweight and obese adults from the general population by performing a systematic review and meta-analysis through mining the existing epidemiological data on fatty liver disease. METHODS We searched Medline, Embase, Web of Science, Cochrane and google scholar database from inception to November, 2020. DerSimonian-Laird random-effects model with Logit transformation was performed for data analysis. Sensitivity analysis and meta-regression were used to explore predictors of MAFLD prevalence in pooled statistics with high heterogeneity. RESULTS We identified 116 relevant studies comprised of 2,667,052 participants in general population with an estimated global MAFLD prevalence as 50.7% (95% CI 46.9-54.4) among overweight/obese adults regardless of diagnostic techniques. Ultrasound was the most commonly used diagnostic technique generating prevalence rate of 51.3% (95% CI, 49.1-53.4). Male (59.0%; 95% CI, 52.0-65.6) had a significantly higher MAFLD prevalence than female (47.5%; 95% CI, 40.7-54.5). Interestingly, MAFLD prevalence rates are comparable based on classical NAFLD and non-NAFLD studies in general population. The pooled estimate prevalence of comorbidities such as type 2 diabetes and metabolic syndrome was 19.7% (95% CI, 12.8-29.0) and 57.5% (95% CI, 49.9-64.8), respectively. CONCLUSIONS MAFLD has an astonishingly high prevalence rate in overweight and obese adults. This calls for attention and dedicated action from primary care physicians, specialists, health policy makers and the general public alike.
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Affiliation(s)
- Jiaye Liu
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Ibrahim Ayada
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Xiaofang Zhang
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Ling Wang
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yang Li
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China
| | - Zhongren Ma
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Wanlu Cao
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Mohsen Ghanbari
- Department of Epidemiology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Zhihui Li
- Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands; Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
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25
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Rosas M, Pinneo S, O'Mealy C, Tsang M, Liu C, Kern M, Hooshmand S, Hong MY. Effects of fresh mango consumption on cardiometabolic risk factors in overweight and obese adults. Nutr Metab Cardiovasc Dis 2022; 32:494-503. [PMID: 34953634 DOI: 10.1016/j.numecd.2021.11.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 09/13/2021] [Accepted: 11/02/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND & AIMS In vitro and animal studies show antidiabetic, anti-inflammatory, and cardioprotective properties of mangos. The objective of this study was to examine the effects of fresh mango consumption compared to an isocaloric control snack on body weight, glucose, insulin, lipid profiles, liver function enzymes, inflammation, and antioxidant activity in overweight and obese adults (BMI ≥26 kg/m2). METHODS AND RESULTS In a crossover design, 27 participants consumed 100 kcal/d of fresh mangos or isocaloric low-fat cookies daily for 12 weeks each, separated by a four-week washout period. Blood glucose, C-reactive protein (CRP), and aspartate transaminase activity significantly decreased while total antioxidant capacity significantly increased following mango consumption. There were no significant changes in body weight, body fat %, blood pressure, insulin, or lipid profile following mango consumption. Cookie consumption significantly increased body weight, insulin, CRP, and triglycerides. CONCLUSION These results suggest that relative to the control snack, mangos may improve certain risk factors associated with overweight and obesity including improved glycemic control and reduced inflammation. CLINICAL TRIALS REGISTER NCT03957928.
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Affiliation(s)
- Martin Rosas
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Sherry Pinneo
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Celeste O'Mealy
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Michelle Tsang
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Changqi Liu
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Mark Kern
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Shirin Hooshmand
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA
| | - Mee Young Hong
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, 92182, USA.
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26
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Fraser A, Markovitz AR, Haug EB, Horn J, Romundstad PR, Dalen H, Rich-Edwards J, Åsvold BO. Ten-Year Cardiovascular Disease Risk Trajectories by Obstetric History: A Longitudinal Study in the Norwegian HUNT Study. J Am Heart Assoc 2022; 11:e021733. [PMID: 35014852 PMCID: PMC9238539 DOI: 10.1161/jaha.121.021733] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Women with a history of obstetric complications are at increased risk of cardiovascular disease, but whether they should be specifically targeted for cardiovascular disease (CVD) risk screening is unknown. Methods and Results We used linked data from the Norwegian HUNT (Trøndelag Health) Study and the Medical Birth Registry of Norway to create a population‐based, prospective cohort of parous women. Using an established CVD risk prediction model (A Norwegian risk model for cardiovascular disease), we predicted 10‐year risk of CVD (nonfatal myocardial infarction, fatal coronary heart disease, and nonfatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and high‐density lipoprotein cholesterol, smoking, antihypertensive use, and family history of myocardial infarction). Predicted 10‐year CVD risk scores in women aged between 40 and 60 years were consistently higher in those with a history of obstetric complications. For example, when aged 40 years, women with a history of preeclampsia had a 0.06 percentage point higher mean risk score than women with all normotensive deliveries, and when aged 60 years this difference was 0.86. However, the differences in the proportion of women crossing established clinical thresholds for counseling and treatment in women with and without a complication were modest. Conclusions Findings do not support targeting parous women with a history of pregnancy complications for CVD screening. However, pregnancy complications identify women who would benefit from primordial and primary prevention efforts such as encouraging and supporting behavioral changes to reduce CVD risk in later life.
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Affiliation(s)
- Abigail Fraser
- Population Health Sciences Bristol Medical School University of Bristol Bristol UK.,Medical Research Council Integrative Epidemiology Unit at the University of Bristol Bristol UK
| | - Amanda R Markovitz
- Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA.,Division of Women's Health Brigham and Women's Hospital Boston MA.,Connors Center for Women's Health and Gender BiologyBrigham and Women's Hospital Boston MA.,Mathematica Cambridge MA
| | - Eirin B Haug
- Population Health Sciences Bristol Medical School University of Bristol Bristol UK.,Medical Research Council Integrative Epidemiology Unit at the University of Bristol Bristol UK.,K.G. Jebsen Center for Genetic Epidemiology Department of Public Health and Nursing NTNUNorwegian University of Science and Technology Trondheim Norway
| | - Julie Horn
- HUNT Research Center Department of Public Health and Nursing NTNUNorwegian University of Science and Technology Levanger Norway.,Department of Obstetrics and Gynecology Levanger HospitalNord-Trøndelag Hospital Trust Levanger Norway
| | - Pål Richard Romundstad
- Department of Public Health and Nursing NTNUNorwegian University of Science and Technology Trondheim Norway
| | - Håvard Dalen
- Department of Medicine Levanger HospitalNord-Trøndelag Hospital Trust Levanger Norway.,Department of Circulation and Medical Imaging NTNUNorwegian University of Science and Technology Trondheim Norway.,Cardiac Clinic St Olavs HospitalTrondheim University Hospital Trondheim Norway
| | - Janet Rich-Edwards
- Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA.,Division of Women's Health Brigham and Women's Hospital Boston MA.,Connors Center for Women's Health and Gender BiologyBrigham and Women's Hospital Boston MA
| | - Bjørn Olav Åsvold
- K.G. Jebsen Center for Genetic Epidemiology Department of Public Health and Nursing NTNUNorwegian University of Science and Technology Trondheim Norway.,HUNT Research Center Department of Public Health and Nursing NTNUNorwegian University of Science and Technology Levanger Norway.,Department of Endocrinology Clinic of Medicine St. Olavs HospitalTrondheim University HospitalNorwegian University of Science and TechnologyNorwegian University of Science and Technology Trondheim Norway
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27
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Shaheen M, Schrode KM, Pan D, Kermah D, Puri V, Zarrinpar A, Elisha D, Najjar SM, Friedman TC. Sex-Specific Differences in the Association Between Race/Ethnicity and NAFLD Among US Population. Front Med (Lausanne) 2021; 8:795421. [PMID: 34926533 PMCID: PMC8674562 DOI: 10.3389/fmed.2021.795421] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is spreading worldwide, with a racial/ethnic disparity. We examined the gender role in the racial/ethnic difference in NAFLD in the US population. We analyzed data for 3,292 individuals ≥18 years old from NHANES 2017-2018, a representative sample of the non-institutionalized adult population in the US. Exclusions were subjects with elevated transferrin level, chronic hepatitis B or C, excessive alcohol use, or prescription medications that might cause hepatic steatosis. NAFLD was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values: S0 <238, S1 = 238-259, S2 = 260-290, S3 >290. Data were analyzed using Chi square and multinomial regression. The overall prevalence of NAFLD was 47.9% [S2 = 16.1%, and S3 = 31.8%]. The prevalence of S3 was highest among Mexican Americans (46%), lowest among Blacks (22.7%), 29.9% in other Hispanics and 32.1% in Whites (p < 0.05). It was higher among Mexican American males (54.1%) compared to Mexican American females (37.7%) (p < 0.05). In the adjusted model, Mexican Americans were two times more likely than Whites to have S2 and S3 (p < 0.05). Only male Mexican Americans had higher odds of S2 and S3 relative to male White (p < 0.05). Males had higher odds of S3 relative to non-menopausal females (p < 0.05). There was no difference in the odds of S2 or S3 NAFLD among the menopausal females with or without hormone therapy relative to non-menopausal females (p > 0.05). While Mexican Americans had the highest prevalence of severe NAFLD relative to the other racial/ethnic groups, only male Mexican Americans, but not females, had higher likelihood of both moderate and severe NAFLD relative to Whites. Interventions that specifically target Mexican American males are needed to increase awareness about NAFLD and its prevention.
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Affiliation(s)
- Magda Shaheen
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Katrina M. Schrode
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Deyu Pan
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Dulcie Kermah
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Vishwajeet Puri
- Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States
| | - Ali Zarrinpar
- University of Florida College of Medicine, Gainesville, FL, United States
| | - David Elisha
- College of Medicine, Charles R Drew University, Los Angeles, CA, United States
| | - Sonia M. Najjar
- Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States
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28
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Denova-Gutiérrez E, Lara-Castor L, Hernández-Alcaraz C, Hernández-Ávila M, Aguilar-Salinas C, Kershenobich D, Barquera S. Prevalence and predictors of elevated liver enzyme levels in Mexico: The Mexican National Health and Nutrition Survey, 2016. Ann Hepatol 2021; 26:100562. [PMID: 34653686 DOI: 10.1016/j.aohep.2021.100562] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/18/2021] [Accepted: 03/23/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVE To determine the prevalence of elevated liver enzyme levels and the fatty liver index according to specific sociodemographic, clinical, anthropometric, and metabolic risk factors in Mexican adult population. MATERIAL AND METHODS The present analysis was conducted using data from the Mexican National Health and Nutrition Survey 2016. For the present study, 3,490 adults with complete information on liver enzymes, sociodemographic, lifestyle, and metabolic factors were analyzed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels were determined from blood samples. We computed the fatty liver Index (FLI), as a surrogate marker of non-alcoholic fatty liver disease. The associations are reported as adjusted odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS At the national level, the prevalence of high serum levels of ALT, AST, and GGT were 7.9%, 13.5, and 12.9 respectively. We observed that men had higher prevalences of altered ALT, GGT and FLI compared to women. Additionally, we observe that individuals with obesity, metabolic syndrome and insulin resistance are significantly more likely to present elevated concentrations of AST, ALT, GGT and FLI. Finally, we found that the subjects of the lowest socioeconomic level and indigenous population were more likely to present elevated levels of AST, ALT, GGT, and FLI. CONCLUSION In Mexico, non-alcoholic fatty liver disease affect people with obesity, diabetes, and metabolic syndrome as well as men, subjects of low socioeconomic status, subjects who live in rural areas and indigenous population. Interventions to reduce this condition should be a public health priority.
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Affiliation(s)
- Edgar Denova-Gutiérrez
- Nutrition and Health Research Center, National Institute of Public Health, Cuernavaca, Mexico.
| | - Laura Lara-Castor
- Nutrition and Health Research Center, National Institute of Public Health, Cuernavaca, Mexico; Friedman School of Nutrition Science and Policy, Tufts University, Boston, USA
| | - Cesar Hernández-Alcaraz
- Nutrition and Health Research Center, National Institute of Public Health, Cuernavaca, Mexico
| | - Mauricio Hernández-Ávila
- Dirección de prestaciones económicas y sociales, Instituto Mexicano del Seguro Social (Mexican Institute of Social Security)
| | - Carlos Aguilar-Salinas
- National Institute of Medical Sciences and Nutrition, "Salvador Zubirán", Mexico City, Mexico
| | - David Kershenobich
- National Institute of Medical Sciences and Nutrition, "Salvador Zubirán", Mexico City, Mexico
| | - Simón Barquera
- Nutrition and Health Research Center, National Institute of Public Health, Cuernavaca, Mexico.
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Nuciferine, an active ingredient derived from lotus leaf, lights up the way for the potential treatment of obesity and obesity-related diseases. Pharmacol Res 2021; 175:106002. [PMID: 34826599 DOI: 10.1016/j.phrs.2021.106002] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 11/21/2021] [Accepted: 11/22/2021] [Indexed: 02/07/2023]
Abstract
Obesity, is an increasingly global public health problem associated complications. However, the proven anti-obesity agents are inefficient with adverse side effects; hence attention is being paid to novel drugs from natural resources to manage obesity and obesity-related diseases. Nuciferine (NF) is a high-quality aporphine alkaloid present in lotus leaf. Unlike the chemical drugs, NF elicits anti-obesity, anti-dyslipidemia, anti-hyperglycemic, anti-hypouricemic, anti-inflammatory, and anti-tumor effects, and affinity to neural receptors, and protection against obesity-related diseases. The underlying mechanism of NF includes the regulation of targeted molecules and pathways related to metabolism, inflammation, and cancer and modulation of Ca2+ flux, gut microbiota, and ferroptosis. Besides, the clinical application, availability, pharmacokinetics, pharmaceutics, and security of NF have been established, highlighting the potential of developing NF as an anti-obesity agent. Therefore, this review provides a comprehensive summarization, which sheds light on future research in NF.
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Almahmoud MH, Al Khawaja NM, Alkinani A, Khader Y, Ajlouni KM. Prevalence of fatty liver disease and its associated factors among Jordanian patients with type 2 diabetes mellitus: A cross-sectional study. Ann Med Surg (Lond) 2021; 68:102677. [PMID: 34401141 PMCID: PMC8358152 DOI: 10.1016/j.amsu.2021.102677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/31/2021] [Accepted: 08/03/2021] [Indexed: 01/23/2023] Open
Abstract
Background Diabetes mellitus (DM) is a well-known risk factor for Non-alcoholic fatty liver disease (NAFLD). Patients with type 2 DM (T2DM) who have NAFLD are at a higher risk of developing advanced stages of liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma compared to non-diabetic patients. This study aimed to estimate the prevalence of NAFLD among patients with T2DM, using hepatic ultrasonographic changes combined with derangement of hepatic transaminases level. Materials and methods This cross-sectional study was conducted at the National Center for Diabetes, Endocrinology and Genetics (NCDEG) in Amman, Jordan. A total of 408 patients with T2DM and 90 non-diabetic subjects were included in this study. Body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), lipid parameters and abdominal ultrasonography were measured. Results Using the ultrasonographic criteria for the diagnosis of NAFLD, the prevalence of NAFLD was 80.4 % and 53.3 % among diabetic and non-diabetic participants, respectively. Among the diabetic participants, 25 %, 40.4 %, and 15 % had mild, moderate, and severe grades of steatosis, respectively. On the other hand, 24.4 %, 21.1 %, and 7.8 % of the non-diabetic participants had mild, moderate, and severe grades of steatosis, respectively. Diabetic patients between 25 and 45 years of age, patients with overweight or obesity, patients with increased waist circumference were significantly at higher risk of having NAFLD. High TG, lower HDL, elevated AST and ALT, and using sulfonylureas and metformin versus using metformin only were significantly associated with increased odds of having NAFLD. Conclusions NAFLD is highly prevalent among patients with T2DM. Overweight or obesity, abnormal cholesterol levels and treatment with sulfonylureas were significantly associated with NAFLD.
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Affiliation(s)
- Malik H Almahmoud
- The National Center for Diabetes, Endocrinology and Genetics, The University of Jordan, Amman, Jordan
| | | | - Arwa Alkinani
- The National Center for Diabetes, Endocrinology and Genetics, The University of Jordan, Amman, Jordan
| | - Yousef Khader
- Department of Public Health, Jordan University of Science and Technology (JUST), Irbid, Jordan
| | - Kamel M Ajlouni
- The National Center for Diabetes, Endocrinology and Genetics, The University of Jordan, Amman, Jordan
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Burra P, Bizzaro D, Gonta A, Shalaby S, Gambato M, Morelli MC, Trapani S, Floreani A, Marra F, Brunetto MR, Taliani G, Villa E. Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Liver Int 2021; 41:1713-1733. [PMID: 33982400 DOI: 10.1111/liv.14943] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 05/05/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Abstract
NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Debora Bizzaro
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Anna Gonta
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | | | - Silvia Trapani
- Italian National Transplant Center, Italian National Institute of Health, Rome, Italy
| | - Annarosa Floreani
- University of Padova, Padua, Italy.,IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Gloria Taliani
- Infectious Diseases Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
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Melaram R. Environmental Risk Factors Implicated in Liver Disease: A Mini-Review. Front Public Health 2021; 9:683719. [PMID: 34249849 PMCID: PMC8264448 DOI: 10.3389/fpubh.2021.683719] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/17/2021] [Indexed: 01/08/2023] Open
Abstract
Liver disease is a global health issue, resulting in about two million deaths per year. It encompasses a wide spectrum of varied or unknown etiologies, ranging from lifestyle choices to pre-existing comorbidities. In recent decades, exposure to environmental toxins and subsequent liver health outcomes have captured public interest, due to the extensive application of pesticides, consumption of aflatoxin contaminated foodstuff, and cyanobacterial harmful algae blooms in endemic regions of liver disease. Hepatocellular carcinoma is a serious and debilitating condition of the liver, characterized by abdominal pain and unexplained weight loss. Established risk factors for hepatocellular carcinoma include alcohol consumption, cigarette smoking, and viral infections of hepatitis B and C. However, mounting evidence suggests that environmental toxins may represent an important contributing factor in hepatocellular carcinoma development. This mini-review synthesizes epidemiological investigations, providing evidence for environmental toxins as one potential risk factor for liver disease.
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Affiliation(s)
- Rajesh Melaram
- School of Health Sciences, Walden University, Minneapolis, MN, United States
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Thong VD, Quynh BTH. Correlation of Serum Transaminase Levels with Liver Fibrosis Assessed by Transient Elastography in Vietnamese Patients with Nonalcoholic Fatty Liver Disease. Int J Gen Med 2021; 14:1349-1355. [PMID: 33889015 PMCID: PMC8057835 DOI: 10.2147/ijgm.s309311] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 03/23/2021] [Indexed: 01/21/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a cause of chronic liver disease, often resulting in liver cirrhosis, portal hypertension, and hepatocellular carcinoma damaging outcomes. Alanine transaminase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury. Several studies have demonstrated that high ALT levels are correlated with higher nonalcoholic steatohepatitis (NASH) risk. The aim was to determine the correlation of serum alanine aminotransferase and aspartate transaminase with liver stiffness in Vietnamese patients with NAFLD. Patients and Methods The study included 18 to 80 years old patients diagnosed with fatty liver on ultrasound at the University of Medical Center (UMC) liver clinic. Liver stiffness was measured using transient elastography. The histopathological, demographic, and laboratory data of the participants were also collected. The baseline and clinical characteristics of NAFLD patients were stratified by serum ALT levels. Results There were 138 NAFLD patients, including 82 men (59.4%) and 56 women (40.6%) (mean ± SD age of 41 ± 11 years). Liver fibrosis (F0) between the two groups showed no significant difference (p = 0.469). Similarly, no difference was found in the mild fibrosis level (F2) of the two groups of patients (p = 0.371). ALT level was significantly higher in NAFLD patients with advanced fibrosis (F3, F4) (3.2% vs 15.9%, p = 0.0013; 3.2% vs 13.2%, p = 0.0047, respectively). NAFLD patients with mild to moderate fibrosis (F1-F2) were detected at 59 U/L cut-off value with 67% sensitivity and 51% specificity. However, severe fibrosis and/or cirrhosis patients (F3-F4) had a cut-off value of 81 U/L with 53% sensitivity and 67% specificity in patients. Conclusion Using ALT level as a marker for severe NAFLD would consider high-risk patients as mild cases, even though there is still the risk of progressive and severe hepatic disease. Our study underlines the small contribution of ALT as an independent factor for detecting NAFLD severity.
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Affiliation(s)
- Vo Duy Thong
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.,Department of Gastroenterology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Bui Thi Huong Quynh
- Department of Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
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Ali N, Sumon AH, Fariha KA, Asaduzzaman M, Kathak RR, Molla NH, Mou AD, Barman Z, Hasan M, Miah R, Islam F. Assessment of the relationship of serum liver enzymes activity with general and abdominal obesity in an urban Bangladeshi population. Sci Rep 2021; 11:6640. [PMID: 33758311 PMCID: PMC7988042 DOI: 10.1038/s41598-021-86216-z] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 03/12/2021] [Indexed: 12/13/2022] Open
Abstract
Obesity is a global health concern because of its increasing trend both in developed and developing countries. A limited number of studies have evaluated the association of liver enzymes with both general and abdominal obesity in the general population; data for the Bangladeshi population are not available yet. This study aimed to assess the relationship of serum liver enzymes activity with both general and abdominal obesity in Bangladeshi adults. In total, 540 blood samples were obtained from the participants (388 males and 152 females) and analyzed for serum levels of ALT, AST, GGT, and ALP using standard methods. General obesity was defined as body mass index (BMI) ≥ 27.5 kg/m2 and abdominal obesity was defined as waist circumference (WC) ≥ 90 cm in males and ≥ 80 cm in females. The relationship between liver enzymes and obesity was evaluated by multivariate logistic regression models. Overall, 58% of participants in the general obesity group and 55% of the participants in the abdominal obesity group had at least one or more elevated levels of liver enzymes. The prevalence of elevated liver enzymes was significantly higher in the obesity group compared to the normal BMI and WC groups (p < 0.05 for all cases). The mean level of serum ALT, AST and GGT were significantly higher in the obesity group than the normal BMI group (p < 0.05). In the WC groups, mean AST and GGT were significantly higher in the obesity group compared to the normal group (p < 0.05). In regression analysis, serum levels of ALT showed an independent and significant association with general obesity, whereas, serum GGT showed a significant association with both general and abdominal obesity. In conclusion, a high prevalence of elevated liver enzymes was observed among participants included in the present study. Of the four enzymes, serum GGT was independently associated with both general and abdominal obesity. Further studies are required to understand the complex relationship between liver enzymes and obesity in the general population.
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Affiliation(s)
- Nurshad Ali
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh.
| | - Abu Hasan Sumon
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Khandaker Atkia Fariha
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Md Asaduzzaman
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Rahanuma Raihanu Kathak
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Noyan Hossain Molla
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Ananya Dutta Mou
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Zitu Barman
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Mahmudul Hasan
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Rakib Miah
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
| | - Farjana Islam
- Department of Biochemistry and Molecular Biology, Shahjalal University of Science and Technology, Sylhet, 3114, Bangladesh
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Association between Dietary Patterns and Serum Hepatic Enzyme Levels in Adults with Dyslipidemia and Impaired Fasting Plasma Glucose. Nutrients 2021; 13:nu13030987. [PMID: 33803758 PMCID: PMC8003213 DOI: 10.3390/nu13030987] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/02/2021] [Accepted: 03/15/2021] [Indexed: 12/17/2022] Open
Abstract
We investigated the association between dietary patterns and serum hepatic enzyme levels in adults with dyslipidemia and impaired fasting glucose in Taiwan. A total of 15,005 subjects (5452 men and 9553 women) aged 35–69 years were selected. Two major dietary patterns were identified by principal component analysis: Western dietary pattern and Mediterranean dietary pattern. Subjects in the highest quartile (Q4) of the Western dietary pattern showed an increased risk of elevated serum alanine aminotransferase (ALT) levels (OR: 1.24, 95% CI: 1.06–1.45, p-trend = 0.01). Fur-thermore, in the highest quartile of the Western dietary pattern, subjects with high waist circum-ference were observed to have a greater risk for developing abnormal serum ALT levels compared to those in the lowest quartile (Q1) (OR: 1.43, 95% CI: 1.04–1.97, p-trend = 0.01). In the highest quartile of the Western dietary pattern, only women were at an increased risk for having abnormal serum ALT levels (OR: 1.28, 95% CI: 1.04–1.59, p-trend = 0.03). By contrast, in the highest quartile of the Mediterranean dietary pattern, only men were at a reduced risk for having abnormal serum gamma-glutamyl transferase (GGT) levels (OR: 0.72, 95% CI: 0.53–0.97, p-trend = 0.048). We report a positive association between the Western dietary pattern and abnormal serum ALT levels.
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The Role of Hepatic Fat Accumulation in Glucose and Insulin Homeostasis-Dysregulation by the Liver. J Clin Med 2021; 10:jcm10030390. [PMID: 33498493 PMCID: PMC7864173 DOI: 10.3390/jcm10030390] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 11/17/2022] Open
Abstract
Accumulation of hepatic triacylglycerol (TG) is associated with obesity and metabolic syndrome, which are important pathogenic factors in the development of type 2 diabetes. In this narrative review, we summarize the effects of hepatic TG accumulation on hepatic glucose and insulin metabolism and the underlying molecular regulation in order to highlight the importance of hepatic TG accumulation for whole-body glucose metabolism. We find that liver fat accumulation is closely linked to impaired insulin-mediated suppression of hepatic glucose production and reduced hepatic insulin clearance. The resulting systemic hyperinsulinemia has a major impact on whole-body glucose metabolism and may be an important pathogenic step in the development of type 2 diabetes.
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Palmieri B, Corazzari V, Panariello Brasile DG, Sangiovanni V, VadalÀ M. Hepatic steatosis integrated approach: nutritional guidelines and joined nutraceutical administration. MINERVA GASTROENTERO 2021; 66:307-320. [PMID: 33443240 DOI: 10.23736/s1121-421x.20.02738-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The nonalcoholic fat liver disease (NAFLD) progresses in 30% of the patients to not alcoholic steatohepatitis (NASH) and subsequently in liver fibrosis and even primary cancer and death. Due to the complex physiopathology of the liver steatosis, NASH is an area orphan of specific drugs, but many authors suggest an integrated treatment based upon diet, lifestyle change, and pharmacology. METHODS Our clinical study selected from a wider patient cohort, 13 subjects, appealing to the Second Opinion Medical Consulting Network, for liver and nutritional problems. The diet was integrated with regular prescription of an herbal derivative based on Chrysanthellum americanum and Pistacia lentiscus L. extracts. Clinical data of the recruited patients including body weight, Body Mass Index, were recorded before and after treatment. Each patient underwent pre-post accurate clinical examination and lab exams. The liver stiffness and liver steatosis were evaluated by a trained hepatologist with FibroScan®. RESULTS A significant reduction of anthropometric parameters was detected in all the patients at the end of the study; liver fibrosis and steatosis were instrumentally decreased in 8 subjects, but not significant changes in lab exams and no adverse effects were reported. CONCLUSIONS Chrysanthellum americanum and Pistacia lentiscus L. extracts were absolutely safe and effective and gave a substantial contribution to the life quality benefit, metabolic balance and gut function in patients with hepatic steatosis.
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Affiliation(s)
- Beniamino Palmieri
- Second Opinion Medical Network, Modena, Italy.,Medico Cura Te Stesso Onlus, Modena, Italy
| | - Veronica Corazzari
- Second Opinion Medical Network, Modena, Italy - .,Medico Cura Te Stesso Onlus, Modena, Italy
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Bekkelund SI. Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study. BMC Cardiovasc Disord 2021; 21:29. [PMID: 33435884 PMCID: PMC7805181 DOI: 10.1186/s12872-020-01826-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 12/14/2020] [Indexed: 12/18/2022] Open
Abstract
Background High and low levels of serum alanine aminotransferase (ALT) are both associated with cardiovascular diseases (CVD) risks especially in elderly, but the mechanisms are less known. This study investigated associations between ALT and CVD risk factors including effects of sex and age in a Caucasian population. Methods Cross-sectional data were analysed sex-stratified in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years) from the population study Tromsø 6. Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT. Risk factors included body mass index (BMI), waist-to-hip-ratio, blood pressure, lipids, glucose, glycated haemoglobin and high-sensitive C-reactive protein (CRP). Results Abnormal elevated ALT was detected in 113 men (4.4%) and 188 women (6.6%). Most CVD risk factors associated positively with ALT in both sexes except systolic blood pressure and CRP (women only), while ALT was positively associated with age in men when adjusted for CVD risk factors, P < 0.001. BMI predicted ALT in men (OR 0.94; 95% CI 0.88–1.00, P = 0.047) and women (OR 0.90; 95% CI 0.86–0.95, P < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60 and 64 years were found. Conclusion This study confirms a positive relationship between ALT and CVD risk factors, particularly BMI. Age is not a major confounder in the ALT-CVD relationship, but separate sex-analyses is recommended in such studies.
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Affiliation(s)
- Svein Ivar Bekkelund
- Department of Clinical Medicine, UiT - The Arctic University of Norway, 9037, Tromsø, Norway. .,Department of Neurology, University Hospital of North Norway, 9038, Tromsø, Norway.
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Claus M, Antoni C, Hofmann B. Factors associated with elevated alanine aminotransferase in employees of a German chemical company: results of a large cross-sectional study. BMC Gastroenterol 2021; 21:25. [PMID: 33422007 PMCID: PMC7797104 DOI: 10.1186/s12876-021-01601-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 01/04/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We aimed to determine the prevalence of elevated alanine aminotransferase (eALT) in employees of a German chemical company, and analyze its association with sociodemographic, work- and lifestyle-related factors. METHODS The cross-sectional study is based on data surveyed from occupational health check-ups between 2013 and 2018 at the site clinic of a chemical company based in Ludwigshafen, Germany. We used logistic regression analyses to assess the association between sociodemographic, work- and lifestyle-related characteristics and eALT. Quantile regression technique was applied to investigate if associations vary across different quantiles of the ALT distribution. RESULTS Participants (n = 15,348) were predominantly male (78.3%) with a mean age of 42.2 years (SD 10.7). The prevalence of eALT was 18.5% (21.6% in men/7.2% in women) with a geometric mean of 28.9 U/L (32.8 U/L in men/18.5 U/L in women). In the multivariable logistic regression model, odds of eALT were significantly higher for males (OR 2.61; 95%-CI 2.24-3.05), manual workers (OR 1.23; 95%-CI 1.06-1.43), overweight (OR 2.66; 95%-CI 2.36-3.00) or obese respondents (e.g. OR 7.88; 95%-CI 5.75-10.80 for obesity class III), employees who consume any number of alcoholic drinks/week (e.g. OR 1.32; 95%-CI 1.16-1.49 for ≥ 3 drinks per week) and diabetics (OR 1.47; 95%-CI 1.22-1.78). Additionally, season of participation was significantly associated with eALT, with odds being higher for participation in spring, fall or winter, as compared to summer. A significant interaction between age and gender (pInteraction < 0.001) was found, showing approximately a u-shaped age/ALT relationship in women and an inversely u-shaped relationship in men. Quantile regression showed an increasing positive effect of male gender, overweight/obesity, and for diabetics on ALT level when moving from the lowest (q0.1) to the highest (q0.9) considered quantile. Additionally, from the lowest to the highest quantile an increasing negative effect on ALT for older age was observed. CONCLUSIONS Prevalence of eALT in our sample of employees can be considered as high, with almost one in five participants affected. Identification of risk groups allows the implementation of targeted preventive measures in order to avoid transition to severe morbidity.
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Affiliation(s)
- Matthias Claus
- Corporate Health Management, ESG/CS - H308, BASF SE, 67056, Ludwigshafen am Rhein, Germany.
| | - Christoph Antoni
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany
| | - Bernd Hofmann
- Corporate Health Management, ESG/CS - H308, BASF SE, 67056, Ludwigshafen am Rhein, Germany
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Prevalence of elevated alanine aminotransferase levels in adult participants from a community-based study from northern part of India. Indian J Gastroenterol 2020; 39:608-613. [PMID: 33098064 DOI: 10.1007/s12664-020-01091-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/01/2020] [Indexed: 02/08/2023]
Abstract
Alanine aminotransferase (ALT) is a cytosolic enzyme specific to hepatocytes, and its elevated level in the peripheral blood denotes liver cell injury. Detection of persistently elevated ALT levels during routine health check-up in asymptomatic or symptomatic individuals provides a window of opportunity to explore the causes of liver cell damage and for the timely institution of appropriate treatment. This was a retrospective study using a subset of the data from a previous community-based prospective study done for the estimation of the prevalence of celiac disease (CD) in India, during which estimation of ALT levels in the blood samples of participants was also carried out. Of the 11,053 individuals (4399 [39.8%] males; mean age 37.9 ± 13.3 years) screened, 6209 consented to provide blood samples for testing for CD. Of these, assessment of serum ALT levels was done in 6083 (2235 [36.7%] males) patients. ALT was elevated above the upper limit of normal (ULN) (> 40 IU/L) in 1246 (20.5%) of the participants and > 1.5 times (> 60 IU/L) in 329 (5.4%) participants. The ALT levels were elevated more frequently in men as compared to women (29.4% vs. 15.3%, p < 0.001). There was a significant positive correlation (Pearson correlation coefficient [r] = 0.25, p < 0.0001) between ALT levels and body mass index (BMI). With increasing age, there was a significant decrease in the proportion of subjects with ALT ≥ 1.5× ULN (p < 0.001). Our results suggest that a high proportion (20.5%) of individuals otherwise considered healthy have values of ALT level in the serum above the "normal" range/cut-off suggesting likely ongoing underlying liver damage. There is a need for measures to evaluate and, if found, treat the underlying cause for the same.
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Chella Krishnan K, Floyd RR, Sabir S, Jayasekera DW, Leon-Mimila PV, Jones AE, Cortez AA, Shravah V, Péterfy M, Stiles L, Canizales-Quinteros S, Divakaruni AS, Huertas-Vazquez A, Lusis AJ. Liver Pyruvate Kinase Promotes NAFLD/NASH in Both Mice and Humans in a Sex-Specific Manner. Cell Mol Gastroenterol Hepatol 2020; 11:389-406. [PMID: 32942044 PMCID: PMC7788245 DOI: 10.1016/j.jcmgh.2020.09.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 08/31/2020] [Accepted: 09/03/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The etiology of nonalcoholic fatty liver disease (NAFLD) is poorly understood, with males and certain populations exhibiting markedly increased susceptibility. Using a systems genetics approach involving multi-omic analysis of ∼100 diverse inbred strains of mice, we recently identified several candidate genes driving NAFLD. We investigated the role of one of these, liver pyruvate kinase (L-PK or Pklr), in NAFLD by using patient samples and mouse models. METHODS We examined L-PK expression in mice of both sexes and in a cohort of bariatric surgery patients. We used liver-specific loss- and gain-of-function strategies in independent animal models of diet-induced steatosis and fibrosis. After treatment, we measured several metabolic phenotypes including obesity, insulin resistance, dyslipidemia, liver steatosis, and fibrosis. Liver tissues were used for gene expression and immunoblotting, and liver mitochondria bioenergetics was characterized. RESULTS In both mice and humans, L-PK expression is up-regulated in males via testosterone and is strongly associated with NAFLD severity. In a steatosis model, L-PK silencing in male mice improved glucose tolerance, insulin sensitivity, and lactate/pyruvate tolerance compared with controls. Furthermore, these animals had reduced plasma cholesterol levels and intrahepatic triglyceride accumulation. Conversely, L-PK overexpression in male mice resulted in augmented disease phenotypes. In contrast, female mice overexpressing L-PK were unaffected. Mechanistically, L-PK altered mitochondrial pyruvate flux and its incorporation into citrate, and this, in turn, increased liver triglycerides via up-regulated de novo lipogenesis and increased PNPLA3 levels accompanied by mitochondrial dysfunction. Also, L-PK increased plasma cholesterol levels via increased PCSK9 levels. On the other hand, L-PK silencing reduced de novo lipogenesis and PNPLA3 and PCSK9 levels and improved mitochondrial function. Finally, in fibrosis model, we demonstrate that L-PK silencing in male mice reduced both liver steatosis and fibrosis, accompanied by reduced de novo lipogenesis and improved mitochondrial function. CONCLUSIONS L-PK acts in a male-specific manner in the development of liver steatosis and fibrosis. Because NAFLD/nonalcoholic steatohepatitis exhibit sexual dimorphism, our results have important implications for the development of personalized therapeutics.
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Affiliation(s)
- Karthickeyan Chella Krishnan
- Department of Medicine/Division of Cardiology, University of California, Los Angeles, California,Correspondence Address correspondence to: Karthickeyan Chella Krishnan, PhD, UCLA Department of Medicine/Division of Cardiology, 650 Charles E. Young Drive South, Box 951679, Los Angeles, California 90095-1679. fax: (310) 794-7345, or
| | - Raquel R. Floyd
- Department of Biology, University of California, Los Angeles, California
| | - Simon Sabir
- Department of Psychology, University of California, Los Angeles, California
| | - Dulshan W. Jayasekera
- Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California
| | - Paola V. Leon-Mimila
- Department of Medicine/Division of Cardiology, University of California, Los Angeles, California,Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Unidad de Genómica de Poblaciones Aplicada a la Salud, Mexico City, Mexico
| | - Anthony E. Jones
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California
| | - Angel A. Cortez
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California
| | - Varun Shravah
- Department of Chemistry, University of California, Los Angeles, California
| | - Miklós Péterfy
- Department of Medicine/Division of Cardiology, University of California, Los Angeles, California,Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, California
| | - Linsey Stiles
- Department of Medicine/Division of Endocrinology, University of California, Los Angeles, California
| | - Samuel Canizales-Quinteros
- Facultad de Química, UNAM/Instituto Nacional de Medicina Genómica (INMEGEN), Unidad de Genómica de Poblaciones Aplicada a la Salud, Mexico City, Mexico
| | - Ajit S. Divakaruni
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California
| | - Adriana Huertas-Vazquez
- Department of Medicine/Division of Cardiology, University of California, Los Angeles, California
| | - Aldons J. Lusis
- Department of Medicine/Division of Cardiology, University of California, Los Angeles, California,Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California,Department of Human Genetics, University of California, Los Angeles, California,Aldons J. Lusis, PhD, UCLA Department of Medicine/Division of Cardiology, 650 Charles E. Young Drive South, Box 951679, Los Angeles, California 90095-1679.
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Perng W, Francis EC, Smith HA, Carey J, Wang D, Kechris KM, Dabelea D. Sex-Specific Metabolite Biomarkers of NAFLD in Youth: A Prospective Study in the EPOCH Cohort. J Clin Endocrinol Metab 2020; 105:dgaa467. [PMID: 32687159 PMCID: PMC7418446 DOI: 10.1210/clinem/dgaa467] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 07/15/2020] [Indexed: 12/16/2022]
Abstract
CONTEXT Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in developed nations. There are currently no accurate biomarkers of NAFLD risk in youth. OBJECTIVE Identify sex-specific metabolomics biomarkers of NAFLD in a healthy cohort of youth. DESIGN/SETTING This prospective study included 395 participants of the EPOCH cohort in Colorado, who were recruited 2006-2009 ("T1 visit") and followed for 5 years ("T2 visit"). We entered 767 metabolites measured at T1 into a reduced rank regression model to identify the strongest determinants of hepatic fat fraction (HFF) at T2, separately for boys and girls. We compared the capacity of metabolites versus conventional risk factors (overweight/obesity, insulin, alanine transaminase, aspartate transaminase) to predict NAFLD (HFF ≥5%) and high HFF (fourth vs first quartile) using area under the receiver operating characteristic curve (AUC). RESULTS Prevalence of NAFLD was 7.9% (8.5% of boys, 7.1% of girls). Mean ± SD HFF was 2.5 ± 3.1%. We identified 13 metabolites in girls and 10 metabolites in boys. Metabolites were in lipid, amino acid, and carbohydrate metabolism pathways. At T1, the metabolites outperformed conventional risk factors in prediction of high HFF but not NAFLD. At T2, the metabolites were superior to conventional risk factors as predictors of high HFF (AUC for metabolites vs conventional risk factors for boys: 0.9565 vs 0.8851, P = 0.02; for girls: 0.9450 vs 0.8469, P = 0.02) with similar trends for NAFLD, although the differences were not significant. CONCLUSIONS The metabolite profiles identified herein are superior predictors of high HFF when assessed 5 years prior and concurrently in a general-risk setting.
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Affiliation(s)
- Wei Perng
- Lifcourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora Colorado
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Colorado
| | - Ellen C Francis
- Lifcourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora Colorado
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Colorado
| | - Harry A Smith
- Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - John Carey
- Lifcourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora Colorado
| | - Dongqing Wang
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Katerina M Kechris
- Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Dana Dabelea
- Lifcourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora Colorado
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Colorado
- Department of Pediatrics, University of Colorado School of Medicine, Aurora Colorado
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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: 17] [Impact Index Per Article: 3.4] [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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Liu Z, Wei R, Li Y. Coronary heart disease is associated with nonalcoholic fatty liver disease in patients without hypertension and diabetes. Medicine (Baltimore) 2020; 99:e20898. [PMID: 32590801 PMCID: PMC7328925 DOI: 10.1097/md.0000000000020898] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
This study was performed to explore the relationship between coronary heart disease (CHD) and nonalcoholic fatty liver disease (NAFLD) in patients without hypertension and diabetes with a focus on predicting CHD.In total, 78 consecutive patients without hypertension and diabetes who were suspected of CHD underwent coronary angiography (CAG) or computed tomography CAG. They were segregated into the CHD and non-CHD group according to the CAG or computed tomography angiography results. The Gensini score was calculated based on CAG results in the CHD group. All patients underwent ultrasonographic measurement of the liver, subcutaneous fat, and visceral fat thickness.The CHD and the Gensini score were significantly correlated with V1, V2, and NAFLD. As the grade of NAFLD increases, the Gensini score was increased. After correcting for confounding factors, NAFLD (B = 2.474, P < .001, 95% confidence interval: 3.32-42.406) and cholesterol (B = 1.176, P = 0.025, 95% confidence interval: 1.155-9.101) were predictor for CHD.The CHD is associated with NAFLD in the patients without hypertension and diabetes. The high-grade NAFLD may be predicted the risk of CHD in patients without hypertension and diabetes.
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Prevalence of Elevated Alanine Aminotransferase by Diagnostic Criterion, Age, and Gender among Adolescents. Gastroenterol Res Pract 2020; 2020:4240380. [PMID: 32411198 PMCID: PMC7204184 DOI: 10.1155/2020/4240380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 12/28/2019] [Indexed: 12/18/2022] Open
Abstract
Background Serum alanine aminotransferase (ALT) activity was measured not only to detect liver disease, but also to monitor overall health. The purpose of this study was to obtain the prevalence of elevated ALT levels among adolescents. Methods In a school-based cross-sectional study, a representative sample was analyzed from 9 middle and high schools in Shenzhen, China, during 2017 to 2018. Elevated ALT was defined as diagnostic criterion I (>30 U/L for boys and >19 U/L for girls) and diagnostic criterion II (>40 U/L). Results From the adolescent population, a total of 7281 students (boys, 4014, and girls, 3267) aged from 10 to 17 years were collected. The prevalence of elevated ALT was 7.11% (6.88% for boys and 7.41% for girls) by criterion I and 2.72% (3.96% for boys and 1.19% for girls) by criterion II. Based on the Shenzhen census and Chinese national census population, the adjusted prevalence of elevated ALT was 7.65% (boys 7.19% and girls 8.21%) and 6.79% (boys 6.07% and girls 7.56%) by criterion I and 2.85% (boys 4.20% and girls 1.16%) and 2.43% (boys 3.49% and girls 1.29%) by criterion II. For age, the overall trends were increasing progressively, regardless of the use of diagnostic criteria for an elevated ALT activity. Conclusions This study supplements the gap that the prevalence of elevated ALT levels differed in gender, age, and criteria among adolescents of Shenzhen. We should take the prevalence as a predictor and continue to play a warning and preventive role in preparation for further intervention.
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Cantoral A, Montoya A, Luna-Villa L, Roldán-Valadez EA, Hernández-Ávila M, Kershenobich D, Perng W, Peterson KE, Hu H, Rivera JA, Téllez-Rojo MM. Overweight and obesity status from the prenatal period to adolescence and its association with non-alcoholic fatty liver disease in young adults: cohort study. BJOG 2020; 127:1200-1209. [PMID: 32145139 DOI: 10.1111/1471-0528.16199] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To examine the associations of maternal and child overweight status across multiple time-points with liver fat content in the offspring during young adulthood. DESIGN Cohort study. SETTING ELEMENT Cohort in Mexico City. POPULATION Pregnant women with singleton births (n = 97). METHODS We quantified hepatic triglyceride content (liver fat content) by proton magnetic resonance spectroscopy (1H MRS) and conventional T2-weighted MRIs (3T scanner) in 97 young adults from the ELEMENT birth cohort in Mexico City. Historical records of the cohort were used as a source of pregnancy, and childhood and adolescence anthropometric information, overweight and obesity (OWOB) were defined. Adjusted structural equation models were run to identify the association between OWOB in different life stages with liver fat content (log-transformed) in young adulthood. MAIN OUTCOME Maternal OWOB at the time of delivery was directly and indirectly associated with the liver fat content in the offspring at young adulthood. RESULTS Seventeen percent of the participants were classified as having NAFLD. We found a strong association of OWOB between all periods assessed. Maternal OWOB at time of delivery (β = 1.97, 95% CI 1.28-3.05), and OWOB status in the offspring at young adulthood (β = 3.17, 95% CI 2.10-4.77) were directly associated with the liver fat content in the offspring. Also, maternal OWOB was indirectly associated with liver fat content through offspring OWOB status. CONCLUSION We found that maternal OWOB status is related to fatty liver content in the offspring as young adults, even after taking into account OWOB status and lifestyle factors in the offspring. TWEETABLE ABSTRACT There was an association between pre-pregnancy overweight and the development of NAFLD in adult offspring.
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Affiliation(s)
- A Cantoral
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - A Montoya
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - L Luna-Villa
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
| | - E A Roldán-Valadez
- Hospital General de México 'Dr. Eduardo Liceaga', Mexico City, Mexico.,Department of Radiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | | | - D Kershenobich
- Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Mexico City, Mexico
| | - W Perng
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - K E Peterson
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.,Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.,Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - H Hu
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.,Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA
| | - J A Rivera
- Instituto Nacional de Salud Pública, Cuernavaca, Mexico
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Cube natural sea salt ameliorates obesity in high fat diet-induced obese mice and 3T3-L1 adipocytes. Sci Rep 2020; 10:3407. [PMID: 32099024 PMCID: PMC7042290 DOI: 10.1038/s41598-020-60462-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 02/07/2020] [Indexed: 01/19/2023] Open
Abstract
Sodium is an essential component of the human body, with known influences on obesity. This paper reports the effect of cube natural sea salt (CNS) on the reduction of obesity in high fat diet-induced obese C57BL/6 mice and 3T3-L1 adipocytes, by ameliorating the obesity parameters and obesity-related gene mechanisms. The suppression of high fat diet-induced obesity and differentiated 3T3-L1 adipocytes by sea salt depends on the manufacturing process and mineral content. The manufacturing method using only new sea water (Cube natural sea salt) decreases the magnesium (Mg) and sulfur (S) content in the salt with different crystallization and morphologies, compared to the general manufacturing method (Generally manufactured sea salt, GS). Mg in salt is known to considerably affect obesity; an appropriate concentration of magnesium chloride (MgCl2) reduces lipid accumulation significantly and regulates the lipogenesis and liver enzyme activity. Our results indicate that sea salt contains an appropriate level of Mg as compared to table salt (purified salt, NaCl), and is important for regulating obesity, as observed in the in vivo and in vitro anti-obesity effects of CNS. The Mg content and mineral ratio of sea salt are important factors that ameliorate the lipid metabolism and liver enzyme activity in high fat diet induced obesity, and contents of Mg in sea salt can be altered by modifying the manufacturing process.
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Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW. Nonalcoholic Fatty Liver Disease in Adults: Current Concepts in Etiology, Outcomes, and Management. Endocr Rev 2020; 41:5601173. [PMID: 31629366 DOI: 10.1210/endrev/bnz009] [Citation(s) in RCA: 141] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 10/14/2019] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disease, extending from simple steatosis to inflammation and fibrosis with a significant risk for the development of cirrhosis. It is highly prevalent and is associated with significant adverse outcomes both through liver-specific morbidity and mortality but, perhaps more important, through adverse cardiovascular and metabolic outcomes. It is closely associated with type 2 diabetes and obesity, and both of these conditions drive progressive disease toward the more advanced stages. The mechanisms that govern hepatic lipid accumulation and the predisposition to inflammation and fibrosis are still not fully understood but reflect a complex interplay between metabolic target tissues including adipose and skeletal muscle, and immune and inflammatory cells. The ability to make an accurate assessment of disease stage (that relates to clinical outcome) can also be challenging. While liver biopsy is still regarded as the gold-standard investigative tool, there is an extensive literature on the search for novel noninvasive biomarkers and imaging modalities that aim to accurately reflect the stage of underlying disease. Finally, although no therapies are currently licensed for the treatment of NAFLD, there are interventions that appear to have proven efficacy in randomized controlled trials as well as an extensive emerging therapeutic landscape of new agents that target many of the fundamental pathophysiological processes that drive NAFLD. It is highly likely that over the next few years, new treatments with a specific license for the treatment of NAFLD will become available.
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Affiliation(s)
- Thomas Marjot
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, UK.,Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
| | - Ahmad Moolla
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
| | - Jeremy F Cobbold
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Leanne Hodson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
| | - Jeremy W Tomlinson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
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Funuyet-Salas J, Martín-Rodríguez A, Conrad R, Pérez-San-Gregorio MÁ. Psychological Biomarker Profile in NAFLD/NASH with Advanced Fibrosis. NAFLD AND NASH 2020:205-223. [DOI: 10.1007/978-3-030-37173-9_12] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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50
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Akinkugbe AA, Barritt AS, Cai J, Offenbacher S, Thyagarajan B, Khambaty T, Singer R, Kallwitz E, Heiss G, Slade GD. Periodontitis and prevalence of elevated aminotransferases in the Hispanic Community Health Study/Study of Latinos. J Periodontol 2019; 89:949-958. [PMID: 29717494 DOI: 10.1002/jper.17-0579] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Revised: 02/07/2018] [Accepted: 02/26/2018] [Indexed: 12/30/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) prevalence is greater among Hispanics/Latinos than other racial/ethnic groups and prevalence is further reported to vary among Hispanic/Latino background groups. Experimental animal and human studies demonstrate associations between periodontitis and NAFLD, not yet reported among Hispanics/Latinos. This study examined periodontitis as a novel risk factor that may contribute to the burden of NAFLD among Hispanics/Latinos. METHODS Data came from 11,914 participants of the Hispanic Community Health Study/Study of Latinos. Periodontitis was defined as the extent (none, < 30%, ≥30%) of periodontal sites with clinical attachment level (CAL) of ≥3 mm or probing pocket depth (PD) of ≥4 mm. Elevated serum transaminases indicative of suspected NAFLD were defined as having alanine aminotransferase levels (ALT) > 40 IU/L or aspartate aminotransferase (AST) > 37 IU/L for men and ALT > 31 IU/L or AST > 31 IU/L for women. Survey-logistic regression models estimated prevalence odds ratios (POR) and 95% confidence intervals (CI) for the association between periodontitis and suspected NAFLD. RESULTS The overall age-standardized percentage of study participants with < 30% of sites with CAL ≥3 mm or PD ≥4 mm was 53.5% and 58.6%, respectively, while participants with ≥30% sites with CAL ≥3 mm or PD ≥4 mm comprised 16% and 5.72%, respectively. The overall age-standardized prevalence (95% CI) of suspected NAFLD was 18.1% (17.1-19.0). For the entire cohort, we observed a dose-response (i.e. graded) association between PD ≥4 mm and the prevalence odds of suspected NAFLD, whereby participants with < 30% affected had a crude POR = 1.19 (95% CI: 1.03, 1.38) while participants with ≥30% affected had a crude POR = 1.39 (95% CI: 1.02, 1.90). These crude estimates were attenuated toward the null and rendered non-significant upon covariate adjustment. No differences were found by Hispanic/Latino background group. CONCLUSION Previously reported associations between periodontitis and NAFLD were marginal to null in this study of a diverse group of Hispanics/Latinos.
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Affiliation(s)
- Aderonke A Akinkugbe
- Oral Health Services Research Core, School of Dentistry, Virginia Commonwealth University, Richmond, VA
| | - A Sidney Barritt
- Department of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Jianwen Cai
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Steven Offenbacher
- Department of Periodontology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Bharat Thyagarajan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
| | - Tasneem Khambaty
- Department of Psychology, University of Maryland, Baltimore County, Baltimore, MD
| | - Richard Singer
- Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL.,College of Dental Medicine, Nova Southeastern University, Ft. Lauderdale, FL
| | - Eric Kallwitz
- Department of Medicine, Loyola University Medical Center, Maywood, IL
| | - Gerardo Heiss
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Gary D Slade
- Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC
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