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Wu Y, Zhou J, Zhang J, Li H. Cytokeratin 18 in nonalcoholic fatty liver disease: value and application. Expert Rev Mol Diagn 2024; 24:1009-1022. [PMID: 39387822 DOI: 10.1080/14737159.2024.2413941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 10/04/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is a common metabolism-related disease worldwide. Although studies have shown that some medications may be effective for treating NAFLD, they do not satisfy the medical requirements, and lifestyle changes are the most basic strategy. Thus, early detection of NAFLD and timely lifestyle interventions are highly important. AREAS COVERED The traditional diagnostic methods for NAFLD are limited by accuracy, cost, and security issues. Cytokeratin 18 (CK18), which is a marker of apoptosis and overall cell death, is an excellent biomarker for NAFLD. Liver fat accumulation in NAFLD triggers the activation of caspases, which increases the CK18 cleavage and its release into the blood. CK18 can help diagnose different stages of NAFLD, especially the nonalcoholic steatohepatitis (NASH) stage. In evaluating the efficacy of the NAFLD treatment and predicting the risk of NAFLD-related diseases, CK18 plays a significant role. EXPERT OPINION CK18 can non-invasively monitor the pathological conditions of NAFLD patients and provide new hope for the early diagnosis of NAFLD. Adding CK18 to the NAFLD diagnostic criteria that are widely used in clinical settings may be efficient for the detection of NAFLD and early effective intervention.
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Affiliation(s)
- Yuan Wu
- School of Medicine, The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Jing Zhou
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Jun Zhang
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
| | - Hongshan Li
- School of Medicine, The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, China
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Kalaiyarasi K, Sanchalika A, Hsien Min L, Wei Ming Y, Vishalkumar S, Kuo Chao Y, Jee Keem L, Sameer J, Terence HCW, Yen Ping T. Transient Elastography Is the Best-Performing Non-Invasive Test of Liver Fibrosis in Obese Asian Patients with Non-Alcoholic Fatty Liver Disease: A Pilot, Cross-Sectional Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:169. [PMID: 38256429 PMCID: PMC10819647 DOI: 10.3390/medicina60010169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/13/2024] [Accepted: 01/15/2024] [Indexed: 01/24/2024]
Abstract
Background and Objectives: The prevalence of NAFLD (non-alcoholic fatty liver disease) is increasing, and up to 64% of Asian patients with NAFLD are obese. Non-invasive tests (NITs) for the assessment of liver fibrosis are increasingly being used, but data on their performance in obese Asian patients are lacking. In this pilot cross-sectional study, we aim to compare the distribution of serum and radiological markers of fibrosis between obese Asian biopsy-proven NAFLD patients with and without fibrosis and estimate the diagnostic accuracies of these indices. Materials and Methods: Obese Asian patients with NAFLD and who had undergone a liver biopsy showing histological evidence of NAFLD were invited to participate. Liver fibrosis was assessed using laboratory (APRI, AAR, BARD, FIB4, NFS, and Asia-Pacific NAFLD advanced fibrosis score) and imaging modalities (TE: transient elastography, MRE: magnetic resonance elastography, and SWU: shear wave ultrasonography). Results: A total of 16 patients were included in the final analysis. On liver biopsy, nine patients (56.3%) had significant fibrosis (F2 or higher), and six of these patients had advanced fibrosis (F3 or higher). F4 fibrosis was present in one patient (6.3%). For the laboratory markers, we found that the BARD score correctly identified five out of six patients with advanced fibrosis (83.4%, p value 0.045). Among all the NITs studied, liver stiffness measured by TE had the highest accuracy of 87.5% in its established threshold of 8.5 kPa for the detection of advanced fibrosis. MRE also performed well (81.2% in 3.64 kPa). Conclusions: In conclusion, TE has performed well in the detection of advanced fibrosis in obese Asian patients with biopsy-proven NAFLD in our pilot study. Further large-scale definitive studies are needed to validate the results of our findings.
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Affiliation(s)
- Kaliyaperumal Kalaiyarasi
- Division of Hepatology and Gastroenterology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore;
| | - Acharyya Sanchalika
- Clinical Research & Innovation Office, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore;
| | - Low Hsien Min
- Division of Radiology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore;
| | - Yap Wei Ming
- Division of Pathology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore;
| | - Shelat Vishalkumar
- Division of General Surgery, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore; (L.J.K.); (J.S.); (H.C.W.T.); (T.Y.P.)
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Yew Kuo Chao
- Division of Hepatology and Gastroenterology, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore;
| | - Low Jee Keem
- Division of General Surgery, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore; (L.J.K.); (J.S.); (H.C.W.T.); (T.Y.P.)
| | - Junnarkar Sameer
- Division of General Surgery, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore; (L.J.K.); (J.S.); (H.C.W.T.); (T.Y.P.)
| | - Huey Cheong Wei Terence
- Division of General Surgery, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore; (L.J.K.); (J.S.); (H.C.W.T.); (T.Y.P.)
| | - Tan Yen Ping
- Division of General Surgery, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng, Singapore 308433, Singapore; (L.J.K.); (J.S.); (H.C.W.T.); (T.Y.P.)
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Ramaiah P, Jamel Baljon K, Alsulami SA, Lindsay GM, Chinnasamy L. Diet quality indices and odds of metabolic dysfunction-associated fatty liver disease: a case-control study. Front Nutr 2024; 10:1251861. [PMID: 38260062 PMCID: PMC10800572 DOI: 10.3389/fnut.2023.1251861] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 11/02/2023] [Indexed: 01/24/2024] Open
Abstract
Objectives There are only limited studies investigating the impact of dietary quality indicators, such as dietary quality index (DQI), dietary diversity score (DDS), and alternative healthy eating index (AHEI), on metabolic dysfunction-associated fatty liver disease (MASLD). Furthermore, these indicators may have different components that could lead to varying results. Therefore, this study aims to assess the nutritional quality indicators and their potential association with MASLD. Methods The study included 128 recently diagnosed MASLD patients and 256 controls aged between 20 and 60 years. The dietary intake of participants was evaluated using a validated semi-quantitative food frequency questionnaire that consisted of 168 items. In this study, the method used to evaluate dietary diversity was based on five main food groups, specifically bread and grains, vegetables, fruits, meat, and dairy. The AHEI-2010 was computed using data collected from the FFQ. Results After adjusting for confounders in the fully adjusted model, a significant negative correlation was observed between DDS and the risk of MASLD (OR 0.41, 95% CI 0.20, 0.97). Participants in the top quartile of AHEI had a 76% lower risk of MASLD compared with those in the bottom quartile after controlling for all potential confounders in the fully adjusted model (OR 0.24, 95% CI 0.12, 0.56). Conclusion The results of our study suggest that there is a significant association between adherence to a high-diversity diet and a reduced likelihood of developing MASLD. Similarly, we observed a similar association between adherence to the AHEI diet and a lower risk of MASLD.
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Affiliation(s)
| | | | - Sana A. Alsulami
- Faculty of Nursing, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Grace M. Lindsay
- Faculty of Nursing, Umm Al-Qura University, Makkah, Saudi Arabia
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Basheer M, Boulos M, Basheer A, Loai A, Nimer A. Olive Oil's Attenuating Effects on Lipotoxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:869-882. [PMID: 39287875 DOI: 10.1007/978-3-031-63657-8_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.
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Affiliation(s)
- Maamoun Basheer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Mariana Boulos
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Areej Basheer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
- Nutrition and Diet Services, Hillel Yaffe, Hadera, Israel
| | - Arraf Loai
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel
| | - Assy Nimer
- Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel.
- Faculty of Medicine at Galilee, Bar-Ilan University, Safed, Israel.
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Peng X, Li J, Zhao H, Lai J, Lin J, Tang S. Lifestyle as well as metabolic syndrome and non-alcoholic fatty liver disease: an umbrella review of evidence from observational studies and randomized controlled trials. BMC Endocr Disord 2022; 22:95. [PMID: 35399069 PMCID: PMC8996397 DOI: 10.1186/s12902-022-01015-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 04/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND & AIMS Recent epidemiological studies have indicated that NAFLD is pathologically associated with a sedentary lifestyle, unhealthy dietary habits and metabolic syndrome. An umbrella review of meta-analyses was performed to summarize the quality of evidence regarding the epidemiologic associations between lifestyle, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD) in regards to risk and treatment. METHODS We searched PubMed, Web of Science and Embase Database from inception until June 1, 2021. Meta-analyses of observational studies and randomized controlled trials (RCTs) examining the associations of lifestyle as well as metabolic syndrome with NAFLD risk or treatment were screened. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their P values, 95% prediction intervals, heterogeneity, and small-study effects. For meta-analyses of RCTs, outcomes with a random-effect P < 0.005 and a high-GRADE assessment were classified as strong evidence. RESULTS A total of 37 publications were included in this review: twenty-two publications reporting 41 meta-analyses of observational studies (37 unique outcomes) and 15 publications reporting 81 meta-analyses of RCTs (63 unique outcomes) met the inclusion criteria. Methodological quality was high for 97% of the included meta-analyses. Quality of evidence was rated high only for the association of sugar-sweetened soda consumption with increased NAFLD risk in meta-analyses of observational studies. Only 3 therapeutic interventions (green tea improving ALT, TG, TC and LDL, omega-3 PUFAs improving HOMR-IR and plasma glucose, and exercise improving RT and ALT) from meta -analyses of RCTs with suggestive (change to high/low/etc) levels of evidence were identified. CONCLUSION Despite many meta-analyses exploring the associations of lifestyle as well as metabolic syndrome with the risk or treatment of NAFLD, robust clinical RCTs are needed to further investigate the associations between lifestyle modifications and incidence of NAFLD or therapeutic effects on disease progression.
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Affiliation(s)
- Xiaojuan Peng
- Department of Endocrinology, Liuzhou People's Hospital, Liuzhou, Guangxi, 545006, PR China
| | - Juan Li
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, PR China
- Department of Infectious Disease, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, PR China
| | - Hailiang Zhao
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, PR China
| | - Junlong Lai
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, PR China
| | - Junqin Lin
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, PR China
| | - Shaohui Tang
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, PR China.
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Huang R, Rao H, Lv F, Nan Y, Ren W, Huang Y, Li J, Tang H, Huang Y, Chalasani N, Wei L. Attitudes of Chinese Patients with Non-alcoholic Fatty Liver Disease Toward Participation in Clinical Trials from a National Multicenter Survey. Ther Innov Regul Sci 2022; 56:464-473. [PMID: 35171499 DOI: 10.1007/s43441-022-00380-6] [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: 10/20/2021] [Accepted: 01/20/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Many new therapies of non-alcoholic fatty liver disease are being evaluated in clinical trials (CTs), but few of these trials involved sites in China. We evaluated influencing factors of Chinese patients' perspectives in participation in CTs of non-alcoholic fatty liver disease. METHODS A questionnaire was designed to be completed by patients with non-alcoholic fatty liver disease at eight affiliated hospitals across China. RESULTS 428 patients were included in this analysis, 63% were male and median age was 37.9 years (30.0-44.0). 54% patients rated "to help others" and 30% "to improve my health status" as the greatest benefit from CTs. The most important concerns were safety (43%) and patients' benefit (26%). Improving liver fibrosis or cirrhosis (53%) and reducing fat in liver (21%) were desired efficacy of new drugs. Possibility of being treated with a placebo for up to 2-6 years played an influential (21%) or very influential (73%) role on participation. Lower education level, lower body mass index, and cirrhosis were positively associated with acceptance of liver biopsies. Anxiety of adverse effects of the new drug and requirement of 2-3 liver biopsies were negatively associated with patients' attitudes toward participating in the trial. CONCLUSION More than one-third of Chinese patients with NAFLD in this survey are willing to participate in CTs of NASH. For CTs of NASH treatment, potential effects on reversing fibrosis or cirrhosis would positively influence, while adverse effects of the new drug and requirement of multiple liver biopsies would negatively influence participation in our study.
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Affiliation(s)
- Rui Huang
- Peking University People's Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing, 100044, China
| | - Huiying Rao
- Peking University People's Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing, 100044, China
| | - Fangfang Lv
- Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, No. 3 Qichun East Street, Hangzhou, Zhejiang, China
| | - Yuemin Nan
- The Third Hospital of Hebei Medical University, No. 139 Ziqiang Street, Shijiazhuang, Hebei, China
| | - Wanhua Ren
- Shandong Provincial Hospital Affiliated To Shandong University, No. 324, Jingwu Street, Jinan, Shandong, China
| | - Yan Huang
- Xiangya Hospital Central South University, No. 87 Xiangya Street, Changsha, Hunan, China
| | - Jun Li
- Jiangsu Province Hospital, No. 300 Guangzhou Street, Nanjing, Jiangsu, China
| | - Hong Tang
- West China School of Medicine/West China Hospital, Sichuan University, No. 37 Guoxue Street, Chengdu, Sichuan, China
| | - Yuan Huang
- Beijing Tsinghua Changgung Hospital, No. 168 Litang Street, Beijing, China
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 1050 Wishard Boulevard, RG 4100, Indianapolis, IN, 46202, USA
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, No. 168, Litang Road, Changping District, Beijing, 102218, China.
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Wang Y, Zhang Y, Yang J, Li H, Wang J, Geng W. Lactobacillus plantarum MA2 Ameliorates Methionine and Choline-Deficient Diet Induced Non-Alcoholic Fatty Liver Disease in Rats by Improving the Intestinal Microecology and Mucosal Barrier. Foods 2021; 10:foods10123126. [PMID: 34945677 PMCID: PMC8701163 DOI: 10.3390/foods10123126] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 12/04/2021] [Accepted: 12/15/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become a highly concerned health issue in modern society. Due to the attentions of probiotics in the prevention of NAFLD, it is necessary to further clarify their roles. In this study, the methionine and choline-deficient (MCD) diet induced NAFLD rats model were constructed and treated with strain L. plantarum MA2 by intragastric administration once a day at a dose of 1 × 108 cfu/g.bw. After 56 days of the therapeutic intervention, the lipid metabolism and the liver pathological damage of the NAFLD rats were significantly improved. The content of total cholesterol (TC) and total triglyceride (TG) in serum were significantly lower than that in the NAFLD group (p < 0.05). Meanwhile, the intestinal mucosal barrier and the structure of intestinal microbiota were also improved. The villi length and the expression of claudin-1 was significantly higher than that in the NAFLD group (p < 0.05). Then, by detecting the content of LPS in the serum and the LPS-TLR4 pathway in the liver, we can conclude that Lactobacillus plantarum MA2 could reduce the LPS by regulating the gut microecology, thereby inhibit the activation of LPS-TLR4 and it downstream inflammatory signaling pathways. Therefore, our studies on rats showed that L. plantarum MA2 has the potential application in the alleviation of NAFLD. Moreover, based on the application of the strain in food industry, this study is of great significance to the development of new therapeutic strategy for NAFLD.
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Nah EH, Cho S, Park H, Noh D, Kwon E, Cho HI. Subclinical steatohepatitis and advanced liver fibrosis in health examinees with nonalcoholic fatty liver disease (NAFLD) in 10 South Korean cities: A retrospective cross-sectional study. PLoS One 2021; 16:e0260477. [PMID: 34818372 PMCID: PMC8612540 DOI: 10.1371/journal.pone.0260477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/10/2021] [Indexed: 01/17/2023] Open
Abstract
Background Nonalcoholic steatohepatitis (NASH) has a risk of progressing to cirrhosis. The prevalence of NASH and its associated risk factors in community populations are relatively unknown. This study aimed to determine the prevalence of NASH and advanced liver fibrosis using magnetic resonance elastography (MRE), and determine those risk factors in health examinees with asymptomatic fatty liver. Methods This study consecutively selected subjects who underwent health checkups at 13 health-promotion centers in 10 Korean cities between 2018 and 2020. Hepatic steatosis and stiffness were assessed using ultrasonography and MRE, respectively. Stages of liver stiffness were estimated using MRE with cutoff values for NASH and advanced liver fibrosis of 2.91 and 3.60 kPa, respectively. Results The overall prevalence of NASH and advanced liver fibrosis in the subjects with fatty liver were 8.35% and 2.04%, respectively. Multivariate logistic regression analysis indicated that central obesity (OR = 5.12, 95% CI = 2.70–9.71), increased triglyceride (OR = 3.29, 95% CI = 1.72–6.29), abnormal liver function test (OR = 3.09, 95% CI = 1.66–5.76) (all P<0.001), and decreased high-density lipoprotein cholesterol (OR = 5.18, 95% CI = 1.78–15.05) (P = 0.003) were associated with NASH. The main risk factor for advanced liver fibrosis was diabetes (OR = 4.46, 95% CI = 1.14–17.48) (P = 0.032). Conclusion NASH or advanced liver fibrosis is found in one-tenth of health examinees with asymptomatic fatty liver. This suggests that early detection of NASH should be considered to allow early interventions such as lifestyle changes to prevent the adverse effects of NASH and its progression in health examinees with asymptomatic fatty liver.
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Affiliation(s)
- Eun-Hee Nah
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Seon Cho
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Hyeran Park
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Dongwon Noh
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Eunjoo Kwon
- Health Promotion Research Institute, Korea Association of Health Promotion, Seoul, Korea
| | - Han-Ik Cho
- MEDIcheck LAB, Korea Association of Health Promotion, Seoul, Korea
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Main Risk Factors of Type 2 Diabetes Mellitus with Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2021; 2021:7764817. [PMID: 34691178 PMCID: PMC8528616 DOI: 10.1155/2021/7764817] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/15/2021] [Indexed: 02/06/2023]
Abstract
Type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) is a pathological metabolic disease characterized by high ketone lipid based on abnormal lipid metabolism. Compared with patients with single T2DM or NAFLD, T2DM complicated with NAFLD has more complicated pathogenic factors and pathological processes. Hepatocellular carcinoma (HCC), the leading malignancy arising from cirrhosis, is the second most lethal cancer globally. The purpose of this study was to clarify the main risk factors of T2DM with NAFLD and HCC. There are many challenges in the diagnosis and treatment of T2DM patients with NAFLD and HCC. The current gold standard is to adjust treatment strategy, optimize metabolic control, and improve liver phenotype. It is necessary to identify further the risk factors driving the progression of T2DM with NAFLD and HCC and evaluate new therapeutic targets, in addition to exploring the syndromic forms of T2DM combined with NAFLD and providing a theoretical basis for early prevention, diagnosis, and treatment of the disease using traditional Chinese medicine (TCM).
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Endo T, Koike Y, Miyoshi H, Hisada Y, Fujita R, Suzuki R, Tanaka M, Tsujimoto T, Shimamura Y, Hasegawa Y, Kanayama M, Hashimoto T, Oha F, Noro N, Komano K, Ishii M, Ito YM, Iwasaki N, Takahata M. Close association between non-alcoholic fatty liver disease and ossification of the posterior longitudinal ligament of the spine. Sci Rep 2021; 11:17412. [PMID: 34465807 PMCID: PMC8408257 DOI: 10.1038/s41598-021-96714-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 08/13/2021] [Indexed: 11/30/2022] Open
Abstract
Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age < 70 years, n = 50) was 80.3%, which was 2.5-8 times higher than that in the general Japanese population (9-30%). The ossification index of the spinal ligaments increased in proportion to the severity of fatty liver. The L/S ratio was revealed as a significant risk factor associated with the total ossification index (standardized β: -0.40, 95% confidence interval - 54.34 to - 4.22). This study suggests the potential contribution of NAFLD to the progression of OPLL. The close association between NAFLD and OPLL demonstrated in this study warrants further study to elucidate the causal nature of this relationship.
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Affiliation(s)
- Tsutomu Endo
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Yoshinao Koike
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Hideaki Miyoshi
- Division of Diabetes & Obesity, Faculty of Medicine & Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yuichiro Hisada
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Ryo Fujita
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Ryota Suzuki
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Masaru Tanaka
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Takeru Tsujimoto
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Yukitoshi Shimamura
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Yuichi Hasegawa
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Masahiro Kanayama
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Tomoyuki Hashimoto
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Fumihiro Oha
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Naoki Noro
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Kiyofumi Komano
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Misaki Ishii
- Department of Orthopedics, Hakodate Central General Hospital, 33-2 Hon-cho, Hakodate, Hokkaido, 040-8585, Japan
| | - Yoichi M Ito
- Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Kita-14 Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan
| | - Norimasa Iwasaki
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Masahiko Takahata
- Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
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11
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Carranza-Trejo AM, Vetvicka V, Vistejnova L, Kralickova M, Montufar EB. Hepatocyte and immune cell crosstalk in non-alcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2021; 15:783-796. [PMID: 33557653 DOI: 10.1080/17474124.2021.1887730] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disease in the world. It can evolve into nonalcoholic steatohepatitis (NASH) where inflammation and hepatocyte ballooning are key participants in the determination of this steatotic state.Areas covered: To provide a systematic overview and current understanding of the role of inflammation in NAFLD and its progression to NASH, the function of the cells involved, and the activation pathways of the innate immunity and cell death; resulting in inflammation and chronic liver disease. A PubMed search was made with relevant articles together with relevant references were included for the writing of this review.Expert opinion: Innate and adaptive immunity are the key players in the NAFLD progression; some of the markers presented during NAFLD are also known to be immunity biomarkers. All cells involved in NAFLD and NASH are known to have immunoregulatory properties and their imbalance will completely change the cytokine profile and form a pro-inflammatory microenvironment. It is necessary to fully answer the question of what initiators and metabolic imbalances are particularly important, considering sterile inflammation as the architect of the disease. Due to the shortage of elucidation of NASH progression, we discuss in this review, how inflammation is a key part of this development and we presume the targets should lead to inflammation and oxidative stress treatment.
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Affiliation(s)
| | - Vaclav Vetvicka
- Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY, USA
| | - Lucie Vistejnova
- Biomedical Centre, Medical Faculty in Pilsen, Charles University, Pilsen, Czech Republic
| | - Milena Kralickova
- Biomedical Centre, Medical Faculty in Pilsen, Charles University, Pilsen, Czech Republic
| | - Edgar B Montufar
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
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12
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Bilic-Curcic I, Cigrovski Berkovic M, Virovic-Jukic L, Mrzljak A. Shifting perspectives - interplay between non-alcoholic fatty liver disease and insulin resistance in lean individuals. World J Hepatol 2021; 13:80-93. [PMID: 33584988 PMCID: PMC7856866 DOI: 10.4254/wjh.v13.i1.80] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 10/22/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become a significant public health burden affecting not only obese individuals but also people with normal weight. As opposed to previous beliefs, this particular subset of patients has an increased risk of all-cause mortality and worse outcomes than their obese counterparts. The development of NAFLD in lean subjects seems to be interconnected with metabolic phenotype, precisely visceral fat tissue, sarcopenia, and insulin resistance. Here, we summarize available data focusing on the co-dependent relationship between metabolic phenotype, insulin resistance, and development of NAFLD in lean individuals, suggesting more appropriate tools for measuring body fat distribution for the screening of patients at risk.
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Affiliation(s)
- Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
| | - Lucija Virovic-Jukic
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia.
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13
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Kim H, Min H. Folic acid supplementation prevents high fructose-induced non-alcoholic fatty liver disease by activating the AMPK and LKB1 signaling pathways. Nutr Res Pract 2020; 14:309-321. [PMID: 32765812 PMCID: PMC7390741 DOI: 10.4162/nrp.2020.14.4.309] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/03/2020] [Accepted: 06/29/2020] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND/OBJECTIVES The present study aimed to evaluate the effects of folic acid supplementation in high-fructose-induced hepatic steatosis and clarify the underlying mechanism of folic acid supplementation. MATERIALS/METHODS Male SD rats were fed control, 64% high-fructose diet, or 64% high-fructose diet with folic acid for eight weeks. Plasma glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lipid profiles, hepatic lipid content, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured. RESULTS The HF diet significantly increased hepatic total lipid and triglyceride (TG) and decreased hepatic SAM, SAH, and SAM:SAH ratio. In rats fed a high fructose diet, folic acid supplementation significantly reduced hepatic TG, increased hepatic SAM, and alleviated hepatic steatosis. Moreover, folic acid supplementation in rats fed high fructose enhanced the levels of phosphorylated AMP-activated protein kinase (AMPK) and liver kinase B (LKB1) and inhibited phosphorylation of acetyl coenzyme A carboxylase (ACC) in the liver. CONCLUSIONS These results suggest that the protective effect of folic acid supplementation in rats fed high fructose may include the activation of LKB1/AMPK/ACC and increased SAM in the liver, which inhibit hepatic lipogenesis, thus ameliorating hepatic steatosis. The present study may provide evidence for the beneficial effects of folic acid supplementation in the treatment of non-alcoholic fatty liver disease.
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Affiliation(s)
- Hyewon Kim
- Department of Food and Nutrition, College of Bio-Nano Science, Hannam University, Daejeon 34054, Korea
| | - Hyesun Min
- Department of Food and Nutrition, College of Bio-Nano Science, Hannam University, Daejeon 34054, Korea
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14
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Zeng M, Liu W, Hu Y, Fu N. Sumoylation in liver disease. Clin Chim Acta 2020; 510:347-353. [PMID: 32710938 DOI: 10.1016/j.cca.2020.07.044] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/18/2020] [Accepted: 07/20/2020] [Indexed: 02/07/2023]
Abstract
Small ubiquitin-like modifiers (SUMO) are highly conserved post-translational modification proteins that are present in eukaryotic cells. They are extensively expressed in diverse tissues, including the heart, liver, kidney, and lungs. SUMOylation, a crucial post-translational modification, exhibits a strong effect on DNA repair, transcriptional regulation, protein stability and cell cycle progression. Increasing evidence has demonstrated that SUMOylation is closely related to the development of liver disease. Therefore, the effects of SUMOylation in liver diseases, such as Hepatocellular carcinoma (HCC), viral hepatitis, non-alcoholic fatty liver disease (NAFLD), cirrhosis and primary biliary cirrhosis (PBC) were reviewed in this study. Specifically, SUMO1 was found to promote the invasion and metastasis of HCC and may promote hypoxia-mediated P65 nuclear transport while accelerating the progression of HCC. In addition, SUMO1-modified centrosomal P4.1-associated protein (CAPA) was observed to be overexpressed in Hepatitis B virus (HBV)-related HCC in response to TNF-α stimulation. Furthermore, SUMOylated CAPA was found to induce HBX-triggered NF-κB activation. Considering the diversity and significance of SUMOylation, targeting of the SUMOylation pathway may serve as an effective approach in the treatment of liver diseases.
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Affiliation(s)
- Min Zeng
- Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China
| | - Wenhui Liu
- Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China
| | - Yang Hu
- Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China.
| | - Nian Fu
- Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China.
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15
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Fan SM, Shi XY, Fan YP, Yang LL, Yao J, Feng PM. Efficacy and safety of incretin-based therapies in patients with nonalcoholic fatty liver disease: A protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e20695. [PMID: 32629641 PMCID: PMC7337581 DOI: 10.1097/md.0000000000020695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is seriously affecting the general health due to its high prevalence and associated risk of liver-related consequences and extrahepatic chronic complications. New drugs are urgently needed for the treatment of NAFLD. The purpose of this meta-analysis is to assess the efficacy of incretin-based therapies in patients with NAFLD. METHODS We will search 4 databases for relative studies: PubMed, Cochrane Library, Embase, and Web of Science databases and identified all reports of randomized controlled trials (RCTs) published from inception to July 2020. Two authors will independently scan the searched articles, extract the data from included articles, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model will be used to calculate pooled estimates of weighted mean difference (WMD) with 95% confidence intervals (CIs) or odds ratio (OR) with 95% CIs. RESULTS This systematic review aims to examine the effect of incretin-based therapies on liver histology, liver fat content, liver enzymes, and adverse events in patients with NAFLD. CONCLUSIONS These findings will provide guidance to clinicians and patients on the use of incretin-based therapies for NAFLD.
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Affiliation(s)
- Si-min Fan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Xiao-yan Shi
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Yan-ping Fan
- School of Medicine, Xi’an Jiaotong University, Xi’an, Shanxi Province, P.R. China
| | - Lin-lin Yang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Jia Yao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Pei-min Feng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
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16
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Pitisuttithum P, Chan WK, Piyachaturawat P, Imajo K, Nakajima A, Seki Y, Kasama K, Kakizaki S, Fan JG, Song MJ, Yoon SK, Dan YY, Lesmana L, Ho KY, Goh KL, Wong VWS, Treeprasertsuk S. Predictors of advanced fibrosis in elderly patients with biopsy-confirmed nonalcoholic fatty liver disease: the GOASIA study. BMC Gastroenterol 2020; 20:88. [PMID: 32252638 PMCID: PMC7137333 DOI: 10.1186/s12876-020-01240-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 03/26/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND The Gut and Obesity in Asia (GOASIA) Workgroup was formed to study obesity and gastrointestinal diseases in the Asia Pacific region. We aimed to 1) compare the characteristics of elderly (i.e. age ≥ 60) vs. non-elderly patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD); 2) identify predictors of advanced fibrosis in elderly patients with NAFLD; and 3) assess the performance of non-invasive fibrosis scores in the prediction of advance fibrosis in the elderly population. METHODS We abstracted the data of 1008 patients with NAFLD from nine centers across eight countries. Characteristics of elderly and non-elderly patients with NAFLD were compared using 1:3 sex-matched analysis. RESULTS Of the 1008 patients, 175 were elderly [age 64 (62-67) years], who were matched with 525 non-elderly patients [46 (36-54) years]. Elderly patients were more likely to have advanced fibrosis (35.4% vs. 13.3%; p < 0.001). By multivariable analysis, factors associated with advanced fibrosis in elderly patients included female sex [odds ratio (OR) 3.21; 95% confidence interval (CI) 1.37-7.54] and hypertension (OR 3.68; 95%CI 1.11-12.23). The area under receiver-operating characteristics curve (95% CI) of aspartate aminotransferase-to-platelet ratio index, NAFLD fibrosis score and Fibrosis-4 index for predicting advanced fibrosis in elderly patients were 0.62 (0.52-0.72), 0.65 (0.55-0.75) and 0.64 (0.54-0.74) respectively. CONCLUSIONS Elderly patients with NAFLD had a higher prevalence of advanced fibrosis than non-elderly patients. Female and hypertension were predicting factors for advanced fibrosis in the elderly. Non-invasive fibrosis scores had a lower specificity in elderly.
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Affiliation(s)
| | - Wah Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | | | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yosuke Seki
- Weight Loss and Metabolic Surgery Centre, Yotsuya Medical Cube, Tokyo, Japan
| | - Kazunori Kasama
- Weight Loss and Metabolic Surgery Centre, Yotsuya Medical Cube, Tokyo, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Jian Gao Fan
- Department of Gastroenterology, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Myeong Jun Song
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yock Young Dan
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Laurentius Lesmana
- Digestive Disease and Oncology GI Centre, Medistra Hospital, Jakarta, Indonesia
| | - Khek Yu Ho
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Khean Lee Goh
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Vincent Wai Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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17
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Yoo ER, Kim D, Vazquez-Montesino LM, Escober JA, Li AA, Tighe SP, Fernandes CT, Cholankeril G, Ahmed A. Diet quality and its association with nonalcoholic fatty liver disease and all-cause and cause-specific mortality. Liver Int 2020; 40:815-824. [PMID: 31910319 DOI: 10.1111/liv.14374] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 11/24/2019] [Accepted: 01/03/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD. METHODS We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis. RESULTS Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose-dependent manner. During the median follow-up of 23 years, having a higher diet quality was associated with reduction in risk of all-cause mortality in the age, sex, Race/ethnicity-adjusted hazard ratio (HR) (Q4, HR: 0.60, 95% CI: 0.52-0.68) and the multivariate model (Q4, HR: 0.81, 95% CI: 0.71-0.92). Higher diet quality was associated with a lower risk for all-cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer-related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD. CONCLUSIONS High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer-related and all-cause mortality in those without NAFLD.
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Affiliation(s)
- Eric R Yoo
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | | | - Jessica A Escober
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Andrew A Li
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Sean P Tighe
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Christopher T Fernandes
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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18
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Parsi A, Torkashvand M, Hajiani E, Rahimlou M, Sadeghi N. The effects of crocus sativus extract on serum lipid profile and liver enzymes in patients with non-alcoholic fatty liver disease: A randomized placebo-controlled study. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.obmed.2019.100165] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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19
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Association between non-alcoholic fatty liver disease and coronary calcification depending on sex and obesity. Sci Rep 2020; 10:1025. [PMID: 31974458 PMCID: PMC6978333 DOI: 10.1038/s41598-020-57894-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/08/2020] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome and is associated with cardiovascular outcomes. We investigated whether NAFLD was associated with coronary artery calcification (CAC) in participants without a previous history of cardiovascular disease and whether this association differed according to sex and obesity status after adjustment for other atherosclerosis risk factors, alcohol intake, and liver enzyme levels. Among 67,441 participants, data from 8,705 participants who underwent a fatty liver status and CAC assessment during routine health screening were analysed. CAC scores were calculated using computed tomography. NAFLD was diagnosed in patients with evidence of liver steatosis on ultrasonography. Obesity was defined as a body mass index of ≥25 kg/m2. Multivariate analysis showed a significant association between NAFLD and CAC in non-obese participants (odds ratio, 1.24 [95% confidence interval, 1.01–1.53]), whereas NAFLD and CAC were not associated in obese participants. Interaction analysis showed that the association between NAFLD and CAC was influenced by sex and obesity. Subgroup analysis revealed a significant association between NAFLD and CAC in non-obese male participants (odds ratio, 1.36 [1.07–1.75]), but not in female participants. Our study indicates that non-obese men with NAFLD are prone to CAC.
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20
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Ghaffari A, Rafraf M, Navekar R, Sepehri B, Asghari-Jafarabadi M, Ghavami SM. Turmeric and chicory seed have beneficial effects on obesity markers and lipid profile in non-alcoholic fatty liver disease (NAFLD). INT J VITAM NUTR RES 2019; 89:293-302. [PMID: 31017556 DOI: 10.1024/0300-9831/a000568] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
In an attempt to investigate new strategies aimed at reducing risk factors of non-alcoholic fatty liver disease (NAFLD), effects of turmeric (Curcuma longa L.) and chicory seed (Cichorium intybus L.) supplementation was evaluated in these patients. In this double-blind, randomized, controlled clinical trial, 92 patients with NAFLD aged 20-60 year with body mass index (BMI) ranged 24.9-40 kg/m2 was randomly assigned to 4 groups as follows. 1) Turmeric supplementation (3 g/d) (n = 23, TUR); 2) Chicory seed supplementation (infused 9 g/d (4.5 g /100mL)) (n = 23, CHI); 3) Turmeric and chicory seed supplementation (3 g/d turmeric + infused 9 g/d chicory seed (n = 23, TUR + CHI); 4) Placebo (n = 23, PLA). All intervention periods were 12 weeks. Fasting blood samples, anthropometric measurements, dietary records and physical activity were collected at baseline and at the end of the trial. Significant decreases were observed in BMI and waist circumference (WC) of subjects in CHI and TUR + CHI groups, compared with PLA group (p < 0.05). Combination of turmeric and chicory seed significantly decreased serum alkaline phosphatase level (p < 0.05). Serum levels of HDL-C increased considerably in TUR and TUR + CHI groups (p < 0.05 vs. placebo). Turmeric supplementation alone and plus chicory seed led to significant reduction in serum levels of TG/HDL-C and LDL-C/HDL-C ratio in TUR and TUR + CHI groups in comparison with placebo (p < 0.05). In conclusion, turmeric and chicory seed supplementation can be significantly useful in management of NAFLD risk factors.
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Affiliation(s)
- Aida Ghaffari
- Talented Students Center, Students Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Rafraf
- Professor of Nutrition, Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roya Navekar
- Students Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bita Sepehri
- Assistant professor, Department of Gastroenterology and Hepatology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Asghari-Jafarabadi
- Associate professor, Traffic Injury Prevention Research Center, Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyyed-Mostafa Ghavami
- Associate professor of Radiology, Faculty of paramedical, Tabriz University of Medical Sciences, Tabriz, Iran
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21
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Liu Q, Liu S, Chen L, Zhao Z, Du S, Dong Q, Xin Y, Xuan S. Role and effective therapeutic target of gut microbiota in NAFLD/NASH. Exp Ther Med 2019; 18:1935-1944. [PMID: 31410156 DOI: 10.3892/etm.2019.7781] [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: 01/25/2019] [Accepted: 06/06/2019] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease in the world, is affected by numerous extrinsic and intrinsic factors, including lifestyle, environment, diet, genetic susceptibility, metabolic syndrome and gut microbiota. Accumulating evidence has proven that gut dysbiosis is significantly associated with the development and progression of NAFLD, and several highly variable species in gut microbiota have been identified. The gut microbiota contributes to NAFLD by abnormal regulation of the liver-gut axis, gut microbial components and microbial metabolites, and affects the secretion of bile acids. Due to the key role of the gut microbiota in NAFLD, it has been regarded as a potential target for the pharmacological and clinical treatment of NAFLD. The present review provides a systematic summary of the characterization of gut microbiota and the significant association between the gut microbiota and NAFLD. The possible mechanisms of how the gut microbiota is involved in promoting the development and progression of NAFLD were also discussed. In addition, the potential therapeutic methods for NAFLD based on the gut microbiota were summarized.
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Affiliation(s)
- Qun Liu
- Medical College of Qingdao University, Qingdao, Shandong 266071, P.R. China.,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
| | - Shousheng Liu
- Central Laboratories, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.,Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong 266071, P.R. China
| | - Lizhen Chen
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China.,Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
| | - Zhenzhen Zhao
- Central Laboratories, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.,Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong 266071, P.R. China
| | - Shuixian Du
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
| | - Quanjiang Dong
- Central Laboratories, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.,Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong 266071, P.R. China
| | - Yongning Xin
- Medical College of Qingdao University, Qingdao, Shandong 266071, P.R. China.,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China.,Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong 266071, P.R. China.,Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
| | - Shiying Xuan
- Medical College of Qingdao University, Qingdao, Shandong 266071, P.R. China.,Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China.,Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong 266071, P.R. China
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Vendhan R, Amutha A, Anjana RM, Unnikrishnan R, Mohan V. Clinical profile of nonalcoholic Fatty liver disease among young patients with type 1 diabetes mellitus seen at a diabetes speciality center in India. Endocr Pract 2019; 20:1249-57. [PMID: 25100370 DOI: 10.4158/ep14044.or] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India. METHODS Electronic medical records of T1DM patients (age at first diagnosis of T1DM ≤25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was >500 mg/day, and neuropathy was diagnosed if a patient's vibration perception threshold on biothesiometry was ≥20 V. RESULTS A total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m2, P<.001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P<.05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P<.001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P<.05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P<.05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P<.001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose. CONCLUSIONS This study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy.
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Affiliation(s)
- Ramanujam Vendhan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Anandakumar Amutha
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Ranjit Mohan Anjana
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Ranjit Unnikrishnan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
| | - Viswanathan Mohan
- Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India
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Szanto KB, Li J, Cordero P, Oben JA. Ethnic differences and heterogeneity in genetic and metabolic makeup contributing to nonalcoholic fatty liver disease. Diabetes Metab Syndr Obes 2019; 12:357-367. [PMID: 30936733 PMCID: PMC6430068 DOI: 10.2147/dmso.s182331] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Obesity is the most prevalent noncommunicable disease in the 21st century, associated with triglyceride deposition in hepatocytes leading to nonalcoholic fatty liver disease (NAFLD). NAFLD is now present in around a third of the world's population. Epidemiological studies have concluded that ethnicity plays a role in complications and treatment response. However, definitive correlations of ethnicity with NAFLD are thoroughly under-reported. A comprehensive review was conducted on ethnic variation in NAFLD patients and its potential role as a crucial effector in complications and treatment response. The highest NAFLD prevalence is observed in Hispanic populations, exhibiting a worse disease progression. In contrast, African-Caribbeans exhibit the lowest risk, with less severe steatosis and inflammation, lower levels of triglycerides, and less metabolic derangement, but conversely higher prevalence of insulin resistance. The prevalence of NAFLD in Asian cohorts is under-reported, although reaching epidemic proportions in these populations. The most well-documented NAFLD patient population is that of Caucasian ethnicity, especially from the US. The relative paucity of available literature suggests there is a vital need for more large-scale multi-ethnic clinical cohort studies to determine the incidence of NAFLD within ethnic groups. This would improve therapy and drug development, as well as help identify candidate gene mutations which may differ within the population based on ethnic background.
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Affiliation(s)
- Krisztina B Szanto
- Faculty of Life Sciences and Medicine, School of Medicine, King's College London, London, UK,
- Institute for Liver and Digestive Health, University College London, London, UK,
| | - Jiawei Li
- Institute for Liver and Digestive Health, University College London, London, UK,
- Institute of Child Health, University College London, London, UK
| | - Paul Cordero
- Institute for Liver and Digestive Health, University College London, London, UK,
| | - Jude A Oben
- Institute for Liver and Digestive Health, University College London, London, UK,
- Department of Gastroenterology and Hepatology, Guy's and St Thomas' Hospital, NHS Foundation Trust, London, UK
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Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals. Sci Rep 2019; 9:1814. [PMID: 30755685 PMCID: PMC6372789 DOI: 10.1038/s41598-018-38357-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 12/15/2018] [Indexed: 12/18/2022] Open
Abstract
We aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and cerebral small vessel disease (CSVD) burden, especially according to the NAFLD severity. A total of 1,260 participants were included. The CSVD burden was assessed with white matter hyperintensities (WMH), lacunes, and microbleeds (MBs) on brain MRI. An ultrasound diagnosis of fatty liver was made based on standard criteria, and the Fibrosis-4 (FIB-4) index was used to classify participants with NAFLD with having a high-intermediate (FIB-4 ≥1.45) or low (FIB-4 < 1.45) probability of advanced fibrosis. A multivariable logistic regression analysis was used to assess the association between NAFLD and the presence of moderate to severe WMH, lacunes, and MBs. NAFLD had a significant association only with moderate to severe WMH (OR: 1.64, 95% CI: 1.10-2.42), even after controlling for cardiometabolic risk factors. A linear trend test showed a significant association between the severity of NAFLD fibrosis and the presence of moderate to severe WMH (p for trend <0.001). Our findings suggest that NAFLD, especially NAFLD with fibrosis, has a significant association with the presence of moderate to severe WMH in cognitively normal individuals, and NAFLD severity predicted more frequent moderate to severe WMH.
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Wang X, Ribeiro M, Iracheta-Vellve A, Lowe P, Ambade A, Satishchandran A, Bukong T, Catalano D, Kodys K, Szabo G. Macrophage-Specific Hypoxia-Inducible Factor-1α Contributes to Impaired Autophagic Flux in Nonalcoholic Steatohepatitis. Hepatology 2019; 69:545-563. [PMID: 30102772 PMCID: PMC6351177 DOI: 10.1002/hep.30215] [Citation(s) in RCA: 99] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 08/07/2018] [Indexed: 12/11/2022]
Abstract
Inflammatory cell activation drives diverse cellular programming during hepatic diseases. Hypoxia-inducible factors (HIFs) have recently been identified as important regulators of immunity and inflammation. In nonalcoholic steatohepatitis (NASH), HIF-1α is upregulated in hepatocytes, where it induces steatosis; however, the role of HIF-1α in macrophages under metabolic stress has not been explored. In this study, we found increased HIF-1α levels in hepatic macrophages in methionine-choline-deficient (MCD) diet-fed mice and in macrophages of patients with NASH compared with controls. The HIF-1α increase was concomitant with elevated levels of autophagy markers BNIP3, Beclin-1, LC3-II, and p62 in both mouse and human macrophages. LysMCre HIFdPA fl/fl mice, which have HIF-1α levels stabilized in macrophages, showed higher steatosis and liver inflammation compared with HIFdPA fl/fl mice on MCD diet. In vitro and ex vivo experiments reveal that saturated fatty acid, palmitic acid (PA), both induces HIF-1α and impairs autophagic flux in macrophages. Using small interfering RNA-mediated knock-down and overexpression of HIF-1α in macrophages, we demonstrated that PA impairs autophagy via HIF-1α. We found that HIF-1α mediates NF-κB activation and MCP-1 production and that HIF-1α-mediated impairment of macrophage autophagy increases IL-1β production, contributing to MCD diet-induced NASH. Conclusion: Palmitic acid impairs autophagy via HIF-1α activation in macrophages. HIF-1α and impaired autophagy are present in NASH in vivo in mouse macrophages and in human blood monocytes. We identified that HIF-1α activation and decreased autophagic flux stimulate inflammation in macrophages through upregulation of NF-κB activation. These results suggest that macrophage activation in NASH involves a complex interplay between HIF-1α and autophagy as these pathways promote proinflammatory overactivation in MCD diet-induced NASH.
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Affiliation(s)
- Xiaojing Wang
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA,Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Marcelle Ribeiro
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Arvin Iracheta-Vellve
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Patrick Lowe
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Aditya Ambade
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Abhishek Satishchandran
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Terence Bukong
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Donna Catalano
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Karen Kodys
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
| | - Gyongyi Szabo
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
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Denkmayr L, Feldman A, Stechemesser L, Eder SK, Zandanell S, Schranz M, Strasser M, Huber-Schönauer U, Buch S, Hampe J, Paulweber B, Lackner C, Haufe H, Sotlar K, Datz C, Aigner E. Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients. J Clin Med 2018; 7:E562. [PMID: 30562976 PMCID: PMC6306845 DOI: 10.3390/jcm7120562] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 12/12/2018] [Accepted: 12/14/2018] [Indexed: 12/18/2022] Open
Abstract
A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI ≤ 25.0 kg/m², n confirmed to be appropriate = 74), overweight (BMI > 25.0 ≤ 30.0 kg/m², n = 242) and obese (BMI > 30.0 kg/m², n = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; p = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; p = 0.014) and obese patients (38/150; 25.3%; p = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; p = 0.019) and obese patients (37/150; 24.7%; p = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; p = 0.010) and obese patients (3/150; 2.0% p = 0.027). In total, 60/466; 12.9% patients were diagnosed with non-alcoholic steatohepatitis (NASH). The rate of NASH was higher in lean (14/74; 18.9% p = 0.01) and obese (26/150; 17.3%; p = 0.007) compared to overweight patients (20/242; 8.3%)). Among lean patients, fasting glucose, INR and use of thyroid hormone replacement therapy were independent predictors of NASH in a multivariate model. Lean NAFLD patients were characterized by a severe histological picture similar to obese patients but are more progressed compared to overweight patients. Fasting glucose, international normalized ratio (INR) and the use of thyroid hormone replacement may serve as indicators for NASH in lean patients.
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Affiliation(s)
- Lukas Denkmayr
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Alexandra Feldman
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
- Obesity Research Unit, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Lars Stechemesser
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
- Obesity Research Unit, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Sebastian K Eder
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Stephan Zandanell
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Michael Schranz
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Michael Strasser
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Ursula Huber-Schönauer
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, Austria.
| | - Stephan Buch
- Department of Gastroenterology and Hepatology, Internal Medicine, University Hospital Dresden, 01307 Dresden, Germany.
| | - Jochen Hampe
- Department of Gastroenterology and Hepatology, Internal Medicine, University Hospital Dresden, 01307 Dresden, Germany.
| | - Bernhard Paulweber
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
- Obesity Research Unit, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Carolin Lackner
- Institute of Pathology, Medical University of Graz, 8010 Graz, Austria.
| | - Heike Haufe
- Institute of Pathology, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Karl Sotlar
- Institute of Pathology, Paracelsus Medical University, 5020 Salzburg, Austria.
| | - Christian Datz
- Obesity Research Unit, Paracelsus Medical University, 5020 Salzburg, Austria.
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, 5110 Oberndorf, Austria.
| | - Elmar Aigner
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
- Obesity Research Unit, Paracelsus Medical University, 5020 Salzburg, Austria.
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Effects of turmeric and chicory seed supplementation on antioxidant and inflammatory biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). ADVANCES IN INTEGRATIVE MEDICINE 2018. [DOI: 10.1016/j.aimed.2018.01.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Lim J, Lee H, Ahn J, Kim J, Jang J, Park Y, Jeong B, Yang H, Shin SS, Yoon M. The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice. JOURNAL OF ETHNOPHARMACOLOGY 2018; 225:31-41. [PMID: 29958960 DOI: 10.1016/j.jep.2018.06.034] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 06/12/2018] [Accepted: 06/24/2018] [Indexed: 06/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia. OBJECTIVE This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved. METHODS C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice. RESULTS Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid β-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD. DISCUSSION AND CONCLUSION These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.
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Affiliation(s)
- Jonghoon Lim
- Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea
| | - Haerim Lee
- Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea
| | - Jiwon Ahn
- Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea
| | - Jeongjun Kim
- Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea
| | - Joonseong Jang
- Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea
| | - Yonghyun Park
- Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea
| | - Birang Jeong
- Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Heejung Yang
- Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
| | - Soon Shik Shin
- Department of Formula Sciences, College of Oriental Medicine, Dongeui University, Busan 47340, Republic of Korea.
| | - Michung Yoon
- Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea.
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Yan JH, Guan BJ, Gao HY, Peng XE. Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2018; 97:e12271. [PMID: 30212963 PMCID: PMC6155966 DOI: 10.1097/md.0000000000012271] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 08/16/2018] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Clinical trials examining the therapeutic benefit of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on nonalcoholic fatty liver disease (NAFLD) have reported inconsistent results. We performed a meta-analysis of randomized controlled trials (RCTs) examining the effect of ω-3 PUFA supplementation on NAFLD, and provide substantial evidence on whether ω-3 PUFA supplementation has a favorable effect for treating NAFLD. METHODS We searched the PubMed, Cochrane Library, Springer Link, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific and Technological Journal (VIP) databases for RCTs on oral ω-3 PUFA supplementation in patients with NAFLD. The data were pooled; meta-analyses were conducted using random-effect or fixed-effect models. RESULTS Eighteen studies involving 1424 patients were included. We found a significant benefit for ω-3 PUFAs vs control for liver fat, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, triglycerides, insulin resistance, and glucose. However, there was significant interstudy heterogeneity. Subgroup and regression analyses showed no significantly clear methodologic discrepancy. Publication bias and serious adverse events were not detected. CONCLUSIONS Our meta-analysis suggests that ω-3 PUFA supplementation may decrease liver fat and hepatic enzyme parameters. However, more large-scale, well-designed RCTs are needed to confirm the effect of ω-3 PUFA supplementation on these parameters.
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Affiliation(s)
- Jian-Hui Yan
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University
| | - Bing-Jie Guan
- Department of Tumor Radiology, Fujian Medical University Union Hospital
| | - Hai-Yan Gao
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University
| | - Xian-E Peng
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
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Asgari-Taee F, Zerafati-Shoae N, Dehghani M, Sadeghi M, Baradaran HR, Jazayeri S. Association of sugar sweetened beverages consumption with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Nutr 2018; 58:1759-1769. [PMID: 29761318 DOI: 10.1007/s00394-018-1711-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 05/07/2018] [Indexed: 12/13/2022]
Abstract
PURPOSE The relationship between consumption of sugar sweetened beverages (SSB) and NAFLD has been reported in several epidemiological studies, but the results are inconsistent. The present systematic review and meta-analysis of observational studies was carried out to assess the relationship between sugar sweetened beverages consumption and NAFLD. METHODS Online databases were searched systematically through December, 2016 for studies investigating association between SSB consumption and NAFLD but limited to observational studies in human. Pooled odds ratio (OR) and 95% confidence intervals were calculated using Der-Simonian and Laird method while random effects meta-analysis was used, taking into account conceptual heterogeneity. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic. RESULTS Of the 1015 identified articles, 42 were reviewed in depth and six studies (four cross-sectional, one case-control, and one cohort) met the criteria for inclusion in our systematic review with 6326 participants and 1361 cases of NAFLD in both men and women. Finally, four cross-sectional studies were included in the meta-analysis. Higher intake of SSBs (highest compared to lowest categories) was significantly associated with NAFLD, with a 40% increased Odds of NAFLD after adjusting for important potential confounders (pooled odds ratio 1.40; 95% CI 1.07, 1.82). There was no evidence for significant heterogeneity across studies [P = 0.226 (Q statistics), I2 = 31.0%]. A significant positive association between SSB consumption and NAFLD was observed consistently in a sensitivity analysis [range of summary ORs 1.39-1.49]. There was no evidence of publication bias for the association between SSB and NAFLD. CONCLUSIONS This meta-analysis supports a positive significant association between higher consumption of SSB and NAFLD in both men and women. These findings strengthen the evidence that intake of SSBs should be limited to reduce fatty liver disease.
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Affiliation(s)
- Farzaneh Asgari-Taee
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Nahid Zerafati-Shoae
- Department of Community Nutrition, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Dehghani
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Sadeghi
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hamid R Baradaran
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Shima Jazayeri
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
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Zhang Z, Wang J, Wang H. Correlation of blood glucose, serum chemerin and insulin resistance with NAFLD in patients with type 2 diabetes mellitus. Exp Ther Med 2018; 15:2936-2940. [PMID: 29456698 PMCID: PMC5795563 DOI: 10.3892/etm.2018.5753] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 12/11/2017] [Indexed: 12/25/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a form of clinical syndrome characterized by the fatty degeneration in liver histology and should be further investigated. The aim of the study was to investigate the effects of blood glucose, serum chemerin and insulin resistance on non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus to provide a basis for the prevention and treatment thereof. In total, 300 patients with type 2 diabetes mellitus treated and admitted into the Endocrinology Department of our hospital from June 2015 to June 2017 were enrolled and divided into the simple type 2 diabetes mellitus (group A) and concurrent NAFLD (group B) groups. The sex, age, body mass index (BMI), blood pressure, blood biochemical indexes and chemerin level were compared between the two groups. The patients in group B were further divided into the mild fatty liver (group B1), moderate fatty liver (group B2) and severe fatty liver (group B3) groups. The sex, age, BMI blood pressure, blood biochemical indexes and chemerin level were also compared among the three groups. Finally, the risk factors of type 2 diabetes mellitus complicated by NAFLD were analyzed via logistic regression. The BMI, fasting plasma glucose (FPG), 2 h post-prandial plasma glucose (2hPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-β indexes and serum chemerin level in group B were significantly higher than those in group A (P<0.05 or P<0.01). Notably, the aggravation of NAFLD, the aforementioned indexes were obviously increased (P<0.05 or P<0.01). The regression analysis revealed that BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin were risk factors of concurrent NAFLD. Thus, type 2 diabetes mellitus complicated by NAFLD is closely associated with severe glucose-lipid metabolism disorder and insulin resistance, and BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin constitute risk factors of concurrent NAFLD.
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Affiliation(s)
- Zhengjun Zhang
- Department of Endocrinology, The Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
| | - Jijun Wang
- Department of Internal Medicine, Jining Municipal Government Hospital, Jining, Shandong 272100, P.R. China
| | - Hongmei Wang
- Department of Internal Medicine, Jining Municipal Government Hospital, Jining, Shandong 272100, P.R. China
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He D, Zhang P, Sai X, Li X, Wang L, Xu Y. Camellia euphlebia flower extract inhibits oleic acid-induced lipid accumulation via reduction of lipogenesis in HepG2 cells. Eur J Integr Med 2018. [DOI: 10.1016/j.eujim.2017.11.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Lipotoxicity in Obesity: Benefit of Olive Oil. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 960:607-617. [PMID: 28585218 DOI: 10.1007/978-3-319-48382-5_26] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The clinical implication of Lipotoxicity in obesity derives primarily from its potential to progress to insulin resistance, endothelial dysfunction and atherosclerosis. Olive oil rich diet decrease accumulation of triglyceride in the liver, improved postprandial triglyceride levels, improve glucose and GLP-1 response in insulin resistant subjects, and up regulate GLUT-2 expression in the liver. The exact molecular mechanism is unknown but, decreasing NFkB activation, decreasing LDL oxidation and improving insulin resistance by less production of inflammatory cytokines (TNF-a, IL-6) and improvement of kinases JNK-mediated phosphorylation of IRS-1 are the principle mechanisms. The beneficial effect of the Mediterranean diet derived from monounsaturated fatty acids (MUFA), mainly from olive oil. In this review we document lipotoxicity in obesity and the benefit of olive oil.
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Kwak JH, Jun DW, Lee SM, Cho YK, Lee KN, Lee HL, Lee OY, Choi HS, Yoon BC. Lifestyle predictors of obese and non-obese patients with nonalcoholic fatty liver disease: A cross-sectional study. Clin Nutr 2017; 37:1550-1557. [PMID: 28918170 DOI: 10.1016/j.clnu.2017.08.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Revised: 04/18/2017] [Accepted: 08/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Most people with nonalcoholic fatty liver disease (NAFLD) are obese, and they usually eat more while being less physically active as compared to healthy individuals. However, little is known about the lifestyle patterns of non-obese or obese patients with NAFLD. The aim of this study was to investigate nutrition components and behavioral differences between non-obese and obese patients with NAFLD. METHODS This is a cross-sectional study comprising of 209 patients. Nutritional components and physical activity status were compared in obese and non-obese subjects with NAFLD against healthy controls. Dietary intake was assessed using the 5-day food diary. Physical activity was measured using the protocol of Korea Health and Nutrition Examination Survey. Total and regional body composition analysis was conducted using anthropometry and tetrapolar multi-frequency bio-impedance. Visceral adipose tissue, total abdominal adipose tissue, abdominal subcutaneous adipose tissue as well as liver fat were measured using abdomen tomography. RESULTS Non-obese subjects with NAFLD had higher levels of ALT, AST, GGT, triglyceride, fasting glucose; higher carbohydrate energy ratio; higher visceral fat area, subcutaneous area, body muscle mass, fat free mass and body fat compared to subjects without NAFLD. Subjects with obesity and NAFLD had higher ALT, AST, visceral fat, fasting glucose and HOMA-IR (homeostatic model assessment-insulin resistance), and less moderate-level physical activity compared to those with obesity who do not have NAFLD. Obese subjects with NAFLD also had higher blood pressure, visceral fat area, subcutaneous fat area, body fat, body fat percent and GGT compared to non-obese subjects with NAFLD. In multivariate analysis, carbohydrate energy ratio and physical activity less than moderate-level (<2 h/week) were predictors of NAFLD in non-obese subjects independent of the visceral fat, body muscle index, total energy intake, age and sex. Physical activity less than moderate-level was a predictor of NAFLD in obese subjects with NAFLD, independent of the HOMA-IR, visceral fat, total energy intake, fat energy percent, age and sex. CONCLUSIONS Percentage of carbohydrate intake percent and physical activity, less than moderate-level were independent predictors of NAFLD in non-obese subjects. Meanwhile, physical activity, less than moderate-level, was an independent predictor in obese subjects.
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Affiliation(s)
- Joo Hee Kwak
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
| | - Seung Min Lee
- Department of Food and Nutrition, Sungshin Women's University, 55, Dobong-ro 76ga-gil, Gangbuk-gu, Seoul, Republic of Korea.
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul, Republic of Korea.
| | - Kang Nyeong Lee
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
| | - Hang Lak Lee
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
| | - Oh Young Lee
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
| | - Ho Soon Choi
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
| | - Byung Chul Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seoungdong-gu, Seoul, Republic of Korea.
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Lee HW, Kim BK, Kim SU, Park JY, Kim DY, Ahn SH, Kim KJ, Han KH. Prevalence and Predictors of Significant Fibrosis Among Subjects with Transient Elastography-Defined Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2017; 62:2150-2158. [PMID: 28523578 DOI: 10.1007/s10620-017-4592-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Accepted: 04/25/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIMS Transient elastography (TE) can be used to assess the degree of liver fibrosis and steatosis. We investigated the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) with or without significant liver fibrosis in the general population. METHODS A total of 3033 subjects without alcoholic or chronic viral liver diseases who underwent a medical health check-up including TE were recruited from April 2013 to August 2014. TE-defined NAFLD was defined as a controlled attenuation parameter of ≥250 dB/m, and significant liver fibrosis was defined as a liver stiffness (LS) value of ≥8 kPa. RESULTS Overall, 1178 (42.9%) subjects had NAFLD. Subjects with NAFLD had significantly higher alanine aminotransferase (ALT) levels and a higher prevalence of parameters related to metabolic syndrome, such as high blood pressure, a high body mass index (BMI), glucose intolerance, and dyslipidemia than did subjects without NAFLD (all P < 0.05). Age, male gender, ALT level, serum albumin, BMI, diabetes, hypertriglyceridemia, and LS values independently showed positive associations with the presence of NAFLD (all P < 0.05). In addition, concomitant significant liver fibrosis was identified in 60 (5.1%) subjects with NAFLD, and its independent predictors were age [odds ratio (OR) 1.054], ALT level (OR 1.019), BMI (OR 1.217), and diabetes (OR 1.987) (all P < 0.05). CONCLUSIONS We found that the prevalence of subjects with NAFLD was high (42.9%), and 5.1% of them had concomitant significant liver fibrosis. The risk factors found in this study can help identify which subjects with NAFLD are vulnerable to fibrosis progression.
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Affiliation(s)
- Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Seoul, South Korea
- Brain Korea 21 Project for Medical Science, Seoul, South Korea
| | - Kwang Joon Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Division of Endocrinology, Yonsei University College of Medicine, Seoul, South Korea
- Severance Check-up Severance Hospital, Yonsei University Health System, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea.
- Yonsei Liver Center, Seoul, South Korea.
- Brain Korea 21 Project for Medical Science, Seoul, South Korea.
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The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice. Food Chem Toxicol 2017; 106:292-305. [DOI: 10.1016/j.fct.2017.05.059] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 04/30/2017] [Accepted: 05/26/2017] [Indexed: 02/06/2023]
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Hu Z, Mei S, Xiang J, Zhou J, Li Z, Zhou L, Yan S, Wang W, Zheng S. Survival rates after liver transplantation using hypertensive donor grafts: an analysis of the Scientific Registry of Transplant Recipients database. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2017; 24:441-448. [PMID: 28544515 DOI: 10.1002/jhbp.466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The use of grafts from donors with hypertension (HTN) in liver transplantation has grown rapidly recently, but whether HTN donors affect post-liver transplantation survival is unclear. METHODS We used data from the Scientific Registry of Transplant Recipients database (2004-2008), and evaluated differences in baseline characteristics and outcomes between recipients of grafts from HTN and non-HTN donors. Kaplan-Meier and multivariate Cox regression models were used in assessing patient survival. RESULTS We identified 8,411 recipients of HTN donor grafts (33.2%) and 16,891 (66.8%) recipients of non-HTN donor grafts. Graft and patient survival rates were significantly lower in recipients of HTN donor grafts versus non-HTN donor grafts (1-year, 3-year, and 5-year graft survival rates of 75%, 64%, 50% vs. 80%, 72%, 62% [P < 0.001], respectively, and patient survival rates of 79%, 69%, 56% vs. 83%, 75%, 65% [P < 0.001], respectively). A history of HTN >5 years was also associated with lower rates of graft and patient survival (P < 0.001). A HTN donor was independently associated with a higher risk of graft loss (hazard ratio 1.10, 95% confidence interval 1.01-1.18). CONCLUSION The present study shows that graft and patient survivals were lower in recipients of hypertensive donor grafts, and highlights the importance of appropriately screening donors for HTN.
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Affiliation(s)
- Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Shengmin Mei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Lin Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
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Huang Y, Ye T, Liu C, Fang F, Chen Y, Dong Y. Maternal high-fat diet during pregnancy and lactation affects hepatic lipid metabolism in early life of offspring rat. J Biosci 2017; 42:311-319. [DOI: 10.1007/s12038-017-9675-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Insulin resistance is associated with elevated transaminases and low aspartate aminotransferase/alanine aminotransferase ratio in young adults with normal weight. Eur J Gastroenterol Hepatol 2017; 29:435-440. [PMID: 28009717 DOI: 10.1097/meg.0000000000000811] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE The aim of this study is to determine whether insulin resistance is associated with elevation of transaminases levels and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio in normal-weight healthy young adults. PARTICIPANTS AND METHODS Apparently healthy nonpregnant women and men, aged 18-23 years, were enrolled in a cross-sectional study. According to the homeostasis model assessment of insulin resistance, the participants were allocated into groups of patients with (>2.5) and without (≤2.5) insulin resistance. Normal weight was defined by BMI of at least 18.5 and less than 25.0 kg/m. A multiple logistic regression analysis was carried out to determine the association between insulin resistance and elevated transaminases and AST/ALT ratio of 1 or less. RESULTS A total of 1732 young adults were enrolled and allocated into groups with (n=287) and without (n=1445) insulin resistance. The prevalence of insulin resistance was 16.6% in the overall population. The multivariate logistic regression analysis adjusted by age, sex, waist circumference, and BMI indicated that the odds ratio (OR) between insulin resistance and elevated ALT concentrations is 1.65 [95% confidence interval (CI): 1.04-2.62, P=0.03], for AST/ALT ratio lower than 1 OR is 1.69 (95% CI: 1.27-2.26, P<0.001), and for elevated AST levels OR is 1.31 (95% CI: 0.71-2.43, P=0.377). CONCLUSION The results of the present study suggest that insulin resistance is significantly associated with elevated ALT levels and AST/ALT ratio of lower than 1, but not with elevated AST levels.
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The risk of transient postprandial oxyhypoglycemia in nonalcoholic fatty liver disease. J Gastroenterol 2017; 52:253-262. [PMID: 27351871 DOI: 10.1007/s00535-016-1236-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Accepted: 06/17/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is frequently associated with insulin resistance (IR) and abnormalities in glucose metabolism. Prevalent postprandial hyperinsulinemia along with insulin resistance in NAFLD may lead to hypoglycemia. This study investigated the prevalence of postprandial oxyhypoglycemia in patients with NAFLD. METHODS The oral glucose tolerance test (OGTT) with 75 g glucose was performed in 375 biopsy-proven NAFLD patients with prior unknown type 2 diabetes mellitus (DM). Serum glucose and insulin levels were measured for 3 h after glucose loading and the clinical parameters were compared. RESULTS Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and DM were observed in 36, 36, and 28 %, respectively. Hypoglycemia (≤70 mg/dL) after 3 h was observed in 14.4 % of all patients. The rate of hypoglycemia was significantly higher in NGT (63 % of NGT) than in IGT (30 % of IGT) and DM (7 % of DM) (P < 0.05). In patients with hypoglycemia, the levels of insulin were significantly higher at 30 and 60 min than those without hypoglycemia (P < 0.05). By multivariate analysis, high-LDL cholesterolemia (P < 0.05), low-HDL cholesterolemia (P < 0.05), and fibrosis (P < 0.05) were significant factors that contributed to hypoglycemia after 3 h on 75 g OGTT. CONCLUSIONS A relatively higher proportion of NAFLD cases exhibited transient postprandial hypoglycemia after 3 h on OGTT, especially in NAFLD patients with early-stage fibrosis. By performing 75 g OGTT for 3 h, hypoglycemia would be diagnosed earlier and the treatment intervention would decrease the progression of NAFLD and deterioration of glucose metabolism.
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Sinn DH, Kang D, Chang Y, Ryu S, Gu S, Kim H, Seong D, Cho SJ, Yi BK, Park HD, Paik SW, Song YB, Lazo M, Lima JAC, Guallar E, Cho J, Gwak GY. Non-alcoholic fatty liver disease and progression of coronary artery calcium score: a retrospective cohort study. Gut 2017; 66:323-329. [PMID: 27599521 DOI: 10.1136/gutjnl-2016-311854] [Citation(s) in RCA: 127] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 08/11/2016] [Accepted: 08/16/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, was associated with subclinical atherosclerosis in many cross-sectional studies, but the prospective association between NAFLD and the progression of atherosclerosis has not been evaluated. This study was conducted to evaluate the association between NAFLD and the progression of coronary atherosclerosis. METHODS This retrospective cohort study included 4731 adult men and women with no history of cardiovascular disease (CVD), liver disease or cancer at baseline who participated in a repeated regular health screening examination between 2004 and 2013. Fatty liver was diagnosed by ultrasound based on standard criteria, including parenchymal brightness, liver-to-kidney contrast, deep beam attenuation and bright vessel walls. Progression of coronary artery calcium (CAC) scores was measured using multidetector CT scanners. RESULTS The average duration of follow-up was 3.9 years. During follow-up, the annual rate of CAC progression in participants with and without NAFLD were 22% (95% CI 20% to 23%) and 17% (16% to 18%), respectively (p<0.001). The multivariable ratio of progression rates comparing participants with NAFLD with those without NAFLD was 1.04 (1.02 to 1.05; p<0.001). The association between NAFLD and CAC progression was similar in most subgroups analysed, including in participants with CAC 0 and in those with CAC >0 at baseline. CONCLUSIONS In this large cohort study of adult men and women with no history of CVD, NAFLD was significantly associated with the development of CAC independent of cardiovascular and metabolic risk factors. NAFLD may play a pathophysiological role in atherosclerosis development and may be useful to identify subjects with a higher risk of subclinical disease progression.
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Affiliation(s)
- Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Danbee Kang
- Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.,Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.,Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.,Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Seonhye Gu
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Hyunkyoung Kim
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Donghyeong Seong
- Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Soo Jin Cho
- Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Byoung-Kee Yi
- Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.,Department of Medical Informatics, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Hyung-Doo Park
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Young Bin Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.,Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, USA
| | - Mariana Lazo
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, USA
| | - Joao A C Lima
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, USA
| | - Eliseo Guallar
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, USA
| | - Juhee Cho
- Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.,Center for Cohort Studies, Total Healthcare Screening Center, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, South Korea.,Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.,Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, USA
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
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Makri E, Cholongitas E, Tziomalos K. Emerging role of obeticholic acid in the management of nonalcoholic fatty liver disease. World J Gastroenterol 2016; 22:9039-9043. [PMID: 27895393 PMCID: PMC5107587 DOI: 10.3748/wjg.v22.i41.9039] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 08/31/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid (OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment (FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.
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Chiba T, Suzuki S, Sato Y, Itoh T, Umegaki K. Evaluation of Methionine Content in a High-Fat and Choline-Deficient Diet on Body Weight Gain and the Development of Non-Alcoholic Steatohepatitis in Mice. PLoS One 2016; 11:e0164191. [PMID: 27723801 PMCID: PMC5056759 DOI: 10.1371/journal.pone.0164191] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Accepted: 09/21/2016] [Indexed: 02/06/2023] Open
Abstract
Aim Non-alcoholic steatohepatitis (NASH) is a globally recognized liver disease. A methionine- and choline-deficient diet is used to induce NASH in mice; however, this diet also causes severe body weight loss. To resolve this issue, we examined the effects of methionine content in a high-fat and choline-deficient (HFCD) diet on body weight and the development of NASH in mice. Methods C57BL/6J mice (male, 10 weeks of age) were fed an L-amino acid rodent (control) diet, high-fat (HF) diet, or HFCD diet containing various amounts of methionine (0.1–0.6% (w/w)) for 12 weeks. Plasma lipid levels, hepatic lipid content and inflammatory marker gene expression were measured, and a pathological analysis was conducted to evaluate NASH. Results The 0.1% methionine in HFCD diet suppressed body weight gain, which was lower than that with control diet. On the other hand, the 0.2% methionine in HFCD diet yielded similar body weight gains as the control diet, while more than 0.4% methionine showed the same body weight gains as the HF diet. Liver weights and hepatic lipid contents were the greatest with 0.1% methionine and decreased in a methionine dose-dependent manner. Pathological analysis, NAFLD activity scores and gene expression levels in the liver revealed that 0.1% and 0.2% methionine for 12 weeks induced NASH, whereas 0.4% and 0.6% methionine attenuated the induction of NASH by HFCD diet. However, the 0.2% methionine in HFCD diet did not induce insulin resistance, despite the body weight gain. Conclusions The 0.2% methionine in HFCD diet for 12 weeks was able to induce NASH without weight loss.
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Affiliation(s)
- Tsuyoshi Chiba
- Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan
- * E-mail:
| | - Sachina Suzuki
- Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan
| | - Yoko Sato
- Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan
| | - Tatsuki Itoh
- Department of Food Science and Nutrition, Kinki University Faculty of Agriculture, Nakamachi, Nara, Japan
| | - Keizo Umegaki
- Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-ku, Tokyo, Japan
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Birjandi M, Ayatollahi SMT, Pourahmad S, Safarpour AR. Prediction and Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) and Identification of Its Associated Factors Using the Classification Tree Method. IRANIAN RED CRESCENT MEDICAL JOURNAL 2016; 18:e32858. [PMID: 28191344 PMCID: PMC5292777 DOI: 10.5812/ircmj.32858] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 10/25/2015] [Accepted: 11/22/2015] [Indexed: 12/11/2022]
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in many parts of the world. Objectives The aim of the present study was to identify the most important factors influencing NAFLD using a classification tree (CT) to predict the probability of NAFLD. Patients and Methods This cross-sectional study was conducted in Kavar, a town in the south of Fars province, Iran. A total of 1,600 individuals were selected for the study via the stratified method and multiple-stage cluster random sampling. A total of 30 demographic and clinical variables were measured for each individual. Participants were divided into two datasets: testing and training. We used the training dataset (1,120 individuals) to build the CT and the testing dataset (480 individuals) to assess the CT. The CT was also used to estimate class and to predict fatty liver occurrence. Results NAFLD was diagnosed in 22% of the individuals in the sample. Our findings revealed that the following variables, based on univariate analysis, had a significant association with NAFLD: marital status, history of hepatitis B vaccine, history of surgery, body mass index (BMI), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), triglycerides (TG), alanine aminotransferase (ALT), cholesterol (CHO0, aspartate aminotransferase (AST), glucose (GLU), albumin (AL), and age (P < 0.05). The main affecting variables for predicting NAFLD based on the CT and in order of importance were as follows: BMI, WHR, triglycerides, glucose, SBP, and alanine aminotransferase. The goodness of fit model based on the training and testing datasets were as follows: prediction accuracy (80%, 75%), sensitivity (74%, 73%), specificity (83%, 77%), and the area under the receiver operating characteristic (ROC) curve (78%, 75%), respectively. Conclusions The CT is a suitable and easy-to-interpret approach for decision-making and predicting NAFLD.
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Affiliation(s)
- Mehdi Birjandi
- Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Seyyed Mohammad Taghi Ayatollahi
- Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding Author: Seyyed Mohammad Taghi Ayatollahi, Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel: +98-7132349330, Fax: +98-7132349330, E-mail:
| | - Saeedeh Pourahmad
- Department of Biostatistics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Ali Reza Safarpour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
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Zhang RN, Zheng RD, Mi YQ, Zhou D, Shen F, Chen GY, Zhu CY, Pan Q, Fan JG. APOC3 rs2070666 Is Associated with the Hepatic Steatosis Independently of PNPLA3 rs738409 in Chinese Han Patients with Nonalcoholic Fatty Liver Diseases. Dig Dis Sci 2016; 61:2284-2293. [PMID: 27059980 DOI: 10.1007/s10620-016-4120-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Accepted: 03/06/2016] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIM The association between nonalcoholic fatty liver disease (NAFLD) and apolipoprotein C3 gene (APOC3) promoter region single-nucleotide polymorphisms (SNPs) rs2854117 and rs2854116 is controversial. The aim of this study was to investigate the relationship between other polymorphisms of APOC3 and NAFLD in Chinese. METHODS Fifty-nine liver biopsy-proven NAFLD patients and 72 healthy control subjects were recruited to a cohort representing Chinese Han population. The polymorphisms in the exons and flanking regions of APOC3 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphisms were genotyped. RESULTS Among the five SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) in APOC3, only rs2070666 (c.179 + 62 T/A) was significantly different in genotype and allele frequency (both p < 0.01) between groups of NAFLD and control. After adjusting for sex, age, serum triglycerides, total cholesterol, body mass index, and the PNPLA3 rs738409 polymorphism, the APOC3 rs2070666 A allele was an independent risk factor for NAFLD with an odds ratio (OR) of 3.683 and 95 % confidence interval (CI) of 1.037-13.084. The APOC3 rs2070666 A allele was linked to the fourth quartile of the controlled attenuation parameter values (OR 2.769, 95 % CI 1.002-7.651) in 131 subjects, and also linked to the significant histological steatosis (OR 4.986, 95 % CI 1.020-24.371), but neither to liver stiffness measurement values nor to hepatic histological activity and fibrosis in NAFLD patients. CONCLUSIONS The APOC3 rs2070666 A allele is a risk factor for NAFLD independent of obesity, dyslipidemia, and PNPLA3 rs738409, and it might contribute to increased liver fat content in Chinese Han population.
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Affiliation(s)
- Rui-Nan Zhang
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Rui-Dan Zheng
- Department of Hepatology, Zhengxing Hospital, Zhangzhou, 363000, China
| | - Yu-Qiang Mi
- Department of Infective Disease, Tianjin Infectious Disease Hospital, Tianjin, 300192, China
| | - Da Zhou
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Feng Shen
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Guang-Yu Chen
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Chan-Yan Zhu
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
| | - Qin Pan
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
| | - Jian-Gao Fan
- Department of Gastroenterology and Center for Fatty Liver, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
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Kim S, Park S, Kim B, Kwon J. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease. Sci Rep 2016; 6:27849. [PMID: 27279075 PMCID: PMC4899790 DOI: 10.1038/srep27849] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2016] [Accepted: 05/25/2016] [Indexed: 12/20/2022] Open
Abstract
Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway's IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.
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Affiliation(s)
- Sokho Kim
- Department of Laboratory Animal Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea
| | - Surim Park
- Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea
| | - Bumseok Kim
- Laboratory of Pathology, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea
| | - Jungkee Kwon
- Department of Laboratory Animal Medicine, Chonbuk National University, 79 Gobongro, Iksan, 54596, Republic of Korea
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Tai CM, Huang CK, Tu HP, Hwang JC, Yeh ML, Huang CF, Huang JF, Dai CY, Chuang WL, Yu ML. Interactions of a PPARGC1A Variant and a PNPLA3 Variant Affect Nonalcoholic Steatohepatitis in Severely Obese Taiwanese Patients. Medicine (Baltimore) 2016; 95:e3120. [PMID: 27015186 PMCID: PMC4998381 DOI: 10.1097/md.0000000000003120] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 02/25/2016] [Accepted: 02/26/2016] [Indexed: 12/19/2022] Open
Abstract
The patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant is associated with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, the role of genetic variations of the peroxisome proliferator-activated receptor gamma coactivator-1-alpha gene (PPARGC1A) and glucokinase regulatory (GCKR) gene on NASH in obese patients remains unclear. We studied the effects and interaction of these genetic polymorphisms on NASH in severely obese Taiwanese patients.The genotypes of PPARGC1A rs8192678, PNPLA3 rs738409, and GCKR rs780094 were determined in 177 severely obese patients who underwent bariatric surgery. NASH was evaluated by liver histopathology.Of 177 patients, 29 (16.4%), 57 (33.2%), and 91 (51.4%) were in the non-NAFLD, steatosis, and NASH groups, respectively. We found that the PPARGC1A and PNPLA3 variants, but not the GCKR variant, were associated with NASH. The PPARGC1A rs8192678 GA/AA genotype was associated with higher steatosis grade and presence of ballooning degeneration. The PNPLA3 rs738409 GG genotype was associated with higher severity in all histologic features except for fibrosis. In multivariate analysis, both the PPARGC1A rs8192678 GA/AA genotype (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.08-4.98; P = 0.031) and the PNPLA3 rs738409 GG genotype (OR 4.05; 95% CI 1.24-13.23; P = 0.021), and also body mass index were independent risk factors for NASH. Further, there was an additive effect of the PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype on the presence of NASH (OR 6.83; 95% CI 1.61-29.01; P = 0.009).The PPARGC1A rs8192678 GA/AA genotype and the PNPLA3 rs738409 GG genotype had an additive effect on NASH in severely obese Taiwanese patients.
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Affiliation(s)
- Chi-Ming Tai
- From the Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University (C-MT, C-FH, J-FH, C-YD, W-LC, M-LY); Department of Internal Medicine (C-MT); Department of Bariatric and Metabolic International Surgery Center, E-Da Hospital, I-Shou University (C-MT, C-KH); Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung (H-PT); Department of Pathology, Lin Shin Hospital, Taichung (J-CH); Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung (M-LY, C-FH, J-FH, C-YD, W-LC, M-LY); Faculty of Internal Medicine, School of Medicine, College of Medicine, and Lipid Science and Aging Research Center, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University (M-LY); and Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan (M-LY)
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Yang MH, Sung J, Gwak GY. The associations between apolipoprotein B, A1, and the B/A1 ratio and nonalcoholic fatty liver disease in both normal-weight and overweight Korean population. J Clin Lipidol 2016; 10:289-98. [DOI: 10.1016/j.jacl.2015.11.017] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Revised: 11/20/2015] [Accepted: 11/26/2015] [Indexed: 12/27/2022]
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Fukuda T, Hamaguchi M, Kojima T, Hashimoto Y, Ohbora A, Kato T, Nakamura N, Fukui M. The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals. Liver Int 2016; 36:275-83. [PMID: 26176710 DOI: 10.1111/liv.12912] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 07/06/2015] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on incident type 2 diabetes mellitus (T2DM) in non-overweight individuals with NAFLD. METHODS A population-based retrospective cohort study of 4629 participants who were enrolled in a health check-up programme for more than 10 years. A standardized questionnaire and abdominal ultrasonography were used to diagnose NAFLD. A cut-off point of BMI 23 kg/m(2) was used to define overweight (≥23.0 kg/m(2)) or non-overweight (<23.0 kg/m(2)). The primary outcome was incident T2DM. RESULTS Over a mean follow-up of 12.8 years, 351 participants (7.6%) developed T2DM. The incidence rate of T2DM was 3.2% in the non-overweight without NAFLD group, 14.4% in the non-overweight with NAFLD group, 8.0% in the overweight without NAFLD group and 26.4% in the overweight with NAFLD group. The adjusted hazard ratios for incident T2DM compared with the non-overweight without NAFLD group were as follows: 3.59 (95% CI: 2.14-5.76) in the non-overweight with NAFLD group, 1.99 (95% CI: 1.47-2.69) in the overweight without NAFLD group and 6.77 (95% CI: 5.17-8.91) in the overweight with NAFLD group. The adjusted hazard ratio in the non-overweight with NAFLD group was significantly higher than that in the overweight without NAFLD group or that in the non-overweight without NAFLD group. CONCLUSIONS Non-overweight individuals with NAFLD had a high risk of incident T2DM. Diagnosis of NAFLD is important in non-overweight individuals, and therefore it might be necessary to follow their health conditions on a long-term basis after detection of NAFLD.
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Affiliation(s)
- Takuya Fukuda
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Takao Kojima
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Akihiro Ohbora
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Takahiro Kato
- Department of Internal Medicine, Aiseikai Yamashina Hospital, Kyoto, Japan
| | - Naoto Nakamura
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
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McCarthy EM, Rinella ME. Nonalcoholic Fatty Liver Disease and Steatohepatitis. LIFESTYLE MEDICINE 2016. [DOI: 10.1007/978-3-319-24687-1_29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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