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Zhao Y, Yuan X, Lin T, Yang Q, Jiang X, Yang S, Qiu Y. Combined impact of alcohol consumption and metabolic syndrome on liver dysfunction in an elderly Chinese population. Diabetol Metab Syndr 2024; 16:74. [PMID: 38519973 PMCID: PMC10960482 DOI: 10.1186/s13098-024-01312-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 03/11/2024] [Indexed: 03/25/2024] Open
Abstract
Alcohol consumption and metabolic syndrome(MetS), both prevalent in the general population, frequently co-occur. They are recognized as significant contributors to liver dysfunction, yet their combined effect is often challenging to delineate. This study delves into the compounding influence of alcohol consumption and metabolic disorder on liver dysfunction within an elderly demographic in Zhejiang Province, China. Our findings spotlight a heightened risk of liver dysfunction among females, younger individuals, rural dwellers, those with minimal educational attainment, single individuals, and those diagnosed with MetS. We also discerned a positive correlation correlation between the number of MetS components and the propensity for liver dysfunction. Furthermore, the risk of liver dysfunction escalated in tandem with the frequency of alcohol consumption. Interestingly, a prolonged abstinence period (≥ 5 years) seemed to mitigate this risk. Our research underscores the significance of refraining from excessive alcohol consumption, embracing a healthy lifestyle, and managing MetS components-especially triglyceride levels-for effective prevention of liver dysfunction.
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Affiliation(s)
- Yanrong Zhao
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China
| | - Xiaoxue Yuan
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
- Beijing Institute of Infectious Diseases, Beijing, 100015, China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, China
| | - Tianxiang Lin
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China
| | - Qing Yang
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China
| | - Xuewen Jiang
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China
| | - Song Yang
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, China.
| | - Yinwei Qiu
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China.
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Kityo A, Lee SA. Independent and additive effects of binge drinking and obesity on liver enzymes: a cross-sectional analysis using the Korean National Health Insurance Service data. Gastroenterol Rep (Oxf) 2024; 12:goad074. [PMID: 38222462 PMCID: PMC10784631 DOI: 10.1093/gastro/goad074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 12/07/2023] [Accepted: 12/10/2023] [Indexed: 01/16/2024] Open
Abstract
Background Binge drinking (BD) has been associated with elevated liver enzymes, but the joint association of BD and adiposity with liver enzymes is understudied. We aimed to examine the combined association of BD and obesity with elevated liver enzymes. Methods Data were obtained from 285,600 patients in the Korean National Health check-up program during 2009-2015. Level I BD (BD I) was defined as alcohol consumption of >60 g (men) or >40 g (women) on one occasion in the previous year. High-intensity BD (HIBD) corresponded to at least two times the BD I levels. General and abdominal obesity were defined by body mass index and waist circumference. Logistic regression was used to examine the independent and joint associations of BD and obesity with elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels. Relative excess risk (RERI), attributable proportion (AP), and synergy index (SI) were calculated to estimate the additive interaction effects. Results The mean age was 42.1 ± 0.03 years and 50.2% were women. Elevated ALT [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.16], AST (OR 1.16, 95% CI 1.11-1.23), and GGT (OR 1.84, 95% CI 1.05-1.94) were associated with HIBD. Higher odds of elevated ALT (OR 3.57, 95% CI 3.43-3.71), AST (OR 3.47, 95% CI 3.37-3.58), and GGT (OR 2.10, 95% CI 1.98-2.12) were observed in individuals with general obesity. A similar trend was observed for abdominal obesity. The RERI, AP, and SI for the interaction effect of BD and general obesity were 23%, 7%, and 13% for elevated AST levels, and 67%, 24%, and 58% for elevated GGT levels, respectively. Similar effects were observed for the interaction between BD and abdominal obesity. Conclusions Obesity aggravated the odds of elevated liver AST and GGT levels in HIBD.
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Affiliation(s)
- Anthony Kityo
- Department of Preventive Medicine, School of Medicine, Kangwon National University, Gangwon, Republic of Korea
| | - Sang-Ah Lee
- Department of Preventive Medicine, School of Medicine, Kangwon National University, Gangwon, Republic of Korea
- Interdisciplinary Graduate Program in Medical Bigdata Convergence, Kangwon National University, Gangwon, Republic of Korea
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Patel D, Rathaur P, Parwani K, Patel F, Sharma D, Johar K, Mandal P. In vitro, in vivo, and in silico analysis of synbiotics as preventive interventions for lipid metabolism in ethanol-induced adipose tissue injury. Lipids Health Dis 2023; 22:49. [PMID: 37055787 PMCID: PMC10103406 DOI: 10.1186/s12944-023-01809-z] [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: 12/27/2022] [Accepted: 03/23/2023] [Indexed: 04/15/2023] Open
Abstract
The risk of alcoholic liver disease (ALD) is increased by excessive ethanol drinking. For the prevention of ALD, the effects of ethanol on the liver, adipose tissue, and gut are crucial. Interestingly, garlic and a few probiotic strains can protect against ethanol-induced hepatotoxicity. However, the relationship between adipose tissue inflammation, Kyolic aged garlic extract (AGE), and Lactobacillus rhamnosus MTCC1423 in developing ALD is unknown. Therefore, the present study explored the effect of synbiotics (a combination of prebiotics and probiotics) on adipose tissue to prevent ALD. To investigate the efficacy of synbiotics administration on adipose tissue in preventing ALD, in vitro (3T3-L1 cells, N = 3) groups: control, control + LPS (lipopolysaccharide), ethanol, ethanol + LPS, ethanol + synbiotics, ethanol + synbiotics + LPS; in vivo (Wistar male rats, N = 6) groups: control, ethanol, pairfed, ethanol + synbiotics and in silico experiments were conducted. Lactobacillus multiplies in accordance with the growth curve when exposed to AGE. Additionally, Oil red O staining and scanning electron microscopy (SEM) demonstrated that synbiotics therapy maintained the morphology of adipocytes in the alcoholic model. In support of the morphological changes, quantitative real-time PCR demonstrated overexpression of adiponectin and downregulation of leptin, resistin, PPARγ, CYP2E1, iNOS, IL-6, and TNF-α after administration of synbiotics compared to the ethanol group. In addition, MDA estimation by high-performance liquid chromatography (HPLC) indicated that the synbiotics treatment reduced oxidative stress in rat adipose tissue. Consequently, the in-silico analysis revealed that AGE inhibited the C-D-T networks as PPARγ acting as the main target protein. The current study demonstrates that using synbiotics improves adipose tissue metabolism in ALD.
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Affiliation(s)
- Dhara Patel
- P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa-388421 Gujarat, India
| | - Pooja Rathaur
- Department of Life Science, School of Sciences, Gujarat University, Ahmedabad, 380009 Gujarat India
| | - Kirti Parwani
- P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa-388421 Gujarat, India
| | - Farhin Patel
- P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa-388421 Gujarat, India
| | - Dixa Sharma
- P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa-388421 Gujarat, India
| | - Kaid Johar
- Department of Zoology, Biomedical Technology, and Human Genetics, School of Sciences, Gujarat University, Ahmedabad, 380009 Gujarat India
| | - Palash Mandal
- P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa-388421 Gujarat, India
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Manouchehri S, Mirmohammadi SJ, Vakili M, Mehrparvar AH, Mirzaei M. Association between different patterns of shift work and liver function tests: A cross-sectional analysis of Shahedieh PERSIAN cohort data, Iran, 2020. Work 2023; 76:125-133. [PMID: 36744354 DOI: 10.3233/wor-220110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recent studies suggest that shift work may cause liver dysfunction. OBJECTIVE This study aimed to examine the relationship between different patterns of shift work and elevated level of liver enzymes. METHODS In this cross-sectional study, 1910 workers aged 35 to 70 years were selected with simple random sampling from 9978 participants of the recruitment phase of Shahedieh PERSIAN cohort study. Level of serum liver enzymes (ALT, AST, ALP, and GGT) and ALT/AST ratio was compared between shift workers and non-shift workers, and among employees working in different patterns of shift work. Data were analyzed by SPSS (version 21.0) using Student's T test, Mann-Whitney U test, chi-square test, Kruskal Wallis test, and logistic regression. RESULTS Among 1347 males (71%) and 563 females (29%) with a mean age of 40.4±7.4 years, 469 were shift workers. Fixed evening type shift was the most common (30.3%) and fixed night-shift was the least common (0.9%) type of shift work. The mean blood levels of liver enzymes was not significantly different between shift workers and non-shift workers. In comparison between different patterns of shift work, the mean serum level of GGT was significantly higher in individuals with slow rotating shifts than those with fixed evening shifts, rapid rotating, split and fixed 24 hour shifts (p≤0.001). After adjusting for confounding factors only elevated AST was significantly higher in shift workers. CONCLUSION There was only a significant association between shift work and elevated AST, and no relationship was found with ALT, ALP, GGT, and ALT/AST ratio.
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Affiliation(s)
- Simin Manouchehri
- Department of Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Mahmood Vakili
- Health Monitoring Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Masoud Mirzaei
- Yazd Cardiovascular Research Centre, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Mehlig K, Schult A, Björkelund C, Thelle D, Lissner L. Associations between alcohol and liver enzymes are modified by coffee, cigarettes, and overweight in a Swedish female population. Scand J Gastroenterol 2022; 57:319-324. [PMID: 34874804 DOI: 10.1080/00365521.2021.2009557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
PURPOSE To examine whether positive associations between alcohol and liver enzymes were modified by coffee consumption, smoking, or weight status in a female population. METHODS Regular consumption of beer, wine, and spirits was assessed in a representative cohort of 1462 Swedish women aged 38-60 in 1968, and re-assessed in 1974. In 1980, gamma-glutamyltransferase (GGT) and aspartase transaminase (AST) were measured in 1130 women. Exposures were averaged over values obtained in 1968 and 1974. Multivariable linear regression linked total ethanol intake to log-transformed enzyme values, including interactions by coffee, smoking, and overweight in mutually adjusted models. RESULTS Coffee consumption significantly modified the association between ethanol intake and liver enzymes. One g/day higher ethanol intake was associated with 5.5 (3.5, 7.5)% higher values of GGT, and 1.2 (0.4, 2.1)% higher values of AST in women consuming 0-1 cups of coffee per day, while smaller or no effects were observed in women consuming ≥2 cups/day. Synergistic interactions were observed for ethanol and smoking, and for ethanol and overweight. Average alcohol-related effects on GGT in smokers and non-smokers were given by 3.8 (2.7, 4.9)% and 2.1 (0.9, 3.2)% per g ethanol/day, and by 0.9 (0.4, 1.4)% and 0.2 (-0.3, 0.7)% for AST. Similarly, in overweight women, 1 g/day higher ethanol intake was associated with 4.3 (3.0, 5.6)% higher GGT compared to 1.6 (0.7, 2.5)% in non-overweight women. CONCLUSIONS The results suggest that coffee consumption reduces the enzyme-raising effect of ethanol in the presence of synergistic interactions with smoking and overweight, specifically in women.
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Affiliation(s)
- Kirsten Mehlig
- School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Andreas Schult
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Cecilia Björkelund
- Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Dag Thelle
- School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.,Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Lauren Lissner
- School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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Hwang S, Ren T, Gao B. Obesity and binge alcohol intake are deadly combination to induce steatohepatitis: A model of high-fat diet and binge ethanol intake. Clin Mol Hepatol 2020; 26:586-594. [PMID: 32937687 PMCID: PMC7641546 DOI: 10.3350/cmh.2020.0100] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 06/30/2020] [Indexed: 12/18/2022] Open
Abstract
Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (Cxcl1), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of Cxcl1 and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.
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Affiliation(s)
- Seonghwan Hwang
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Tianyi Ren
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
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Åberg F, Färkkilä M, Männistö V. Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease: A Critical Review of Epidemiological Studies. Alcohol Clin Exp Res 2020; 44:384-403. [DOI: 10.1111/acer.14271] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 12/10/2019] [Indexed: 08/30/2023]
Affiliation(s)
- Fredrik Åberg
- From the Transplantation and Liver Surgery Clinic (FA) Helsinki University Hospital Helsinki University Helsinki Finland
- The Transplant Institute (FA) Sahlgrenska University Hospital Gothenburg Sweden
| | - Martti Färkkilä
- Clinic of Gastroenterology (MF) Helsinki University Hospital Helsinki University Helsinki Finland
| | - Ville Männistö
- Department of Medicine (VM) Kuopio University Hospital University of Eastern Finland Kuopio Finland
- Department of Experimental Vascular Medicine (VM) Amsterdam UMC Location AMC at University of Amsterdam Amsterdam The Netherlands
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Khoudari G, Singh A, Noureddin M, Fritze D, Lopez R, Asaad I, Lawitz E, Poordad F, Kowdley KV, Alkhouri N. Characterization of patients with both alcoholic and nonalcoholic fatty liver disease in a large United States cohort. World J Hepatol 2019; 11:710-718. [PMID: 31749901 PMCID: PMC6856017 DOI: 10.4254/wjh.v11.i10.710] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 08/03/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS) and is characterized by steatosis in the absence of significant alcohol consumption. However, MetS and significant alcohol intake coexist in certain individuals which may lead to the development of BAFLD.
AIM To assess the clinical characteristics of patients with both alcoholic and NAFLD (BAFLD) in a large cohort in the United States.
METHODS Adults from the National Health and Nutrition Examination Survey between 2003-2014 were included. NAFLD was diagnosed based on elevated alanine aminotransferase (ALT) and being overweight or obese in the absence of other liver diseases. BAFLD patients met the criteria for NAFLD but also had either MetS or type 2 diabetes and consumed excessive amounts of alcohol. Univariable and multivariable analysis were performed to assess differences between NAFLD and BAFLD and to compare severity based on a validated fibrosis score (FIB4 index).
RESULTS The prevalence of NAFLD was at 25.9% (95%CI; 25.1-26.8) and that of BAFLD was 0.84% (0.67, 1.02) which corresponds to an estimated 1.24 million Americans affected by BAFLD. Compared to NAFLD, patients with BAFLD were more likely to be male, smokers, have higher ALT, aspartate aminotransferase, triglycerides, and lower platelets; P < 0.01 for all. More importantly, after adjusting for MetS components, BAFLD patients were significantly more likely to have advanced fibrosis [adjusted OR (95%CI) based on FIB4 index > 2.67 was 3.2 (1.4, 7.0), P = 0.004].
CONCLUSION A significant percentage of the American general population is afflicted by BAFLD and these patients tend to have more advanced liver fibrosis.
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Affiliation(s)
- George Khoudari
- Department of Hospital Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
| | - Amandeep Singh
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Mazen Noureddin
- Department of Gastroenterology and Hepatology, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Danielle Fritze
- Department of General Surgery, Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
| | - Rocio Lopez
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Imad Asaad
- Department of Gastroenterology, Metro Health System, Cleveland, OH 44109, United States
| | - Eric Lawitz
- Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
| | - Fred Poordad
- Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
| | - Kris V Kowdley
- Swedish Liver Care Network, Swedish Medical Center, Seattle, WA 98122, United States
| | - Naim Alkhouri
- Texas Liver Institute and University of Texas Health, San Antonio, TX 78215, United States
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Yang Y, Chen Z, Deng L, Yu J, Wang K, Zhang X, Ji G, Li F. Pien Tze Huang ameliorates liver injury by inhibiting the PERK/eIF2α signaling pathway in alcohol and high-fat diet rats. Acta Histochem 2018; 120:578-585. [PMID: 30005895 DOI: 10.1016/j.acthis.2018.06.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 06/15/2018] [Accepted: 06/25/2018] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To explore whether Pien Tze Huang (PTH) exerts a hepatoprotective effect via inhibiting the PERK/eIF2ɑ signaling pathway using an experimental animal model of alcoholic and high-fat diet rats. METHODS A liver injury rat model was established and treated with PTH. Pathological changes in the liver were evaluated by hematoxylin and eosin staining. Hepatic biochemical indexes were detected using an automatic biochemical analyzer. The level of Hcy in serum samples was analyzed using an ELISA. Levels of mRNAs related to ER stress signaling were measured by real-time quantitative-PCR, and protein expression levels were measured by Western blot analysis. RESULTS PTH ameliorated the defects in hepatic function, hepatic pathology and the impairment in lipid metabolism observed in the alcoholic and high-fat diet rats. Moreover, PTH reduced the serum Hcy level and inhibited the PERK/eIF2ɑ pathway in response to ER stress. CONCLUSIONS These results suggest that the administration of PTH ameliorated the severity of alcoholic and high-fat diet rats possibly by inhibiting the Hcy-induced PERK/eIF2α pathway.
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Affiliation(s)
- Yang Yang
- Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China
| | - Zhiliang Chen
- Fujian Provincial Key Laboratory of Pien Tze Huang Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical CO., LTD., Fujiian 363000, People's Republic of China
| | - Lvyu Deng
- Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China
| | - Juan Yu
- Fujian Provincial Key Laboratory of Pien Tze Huang Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical CO., LTD., Fujiian 363000, People's Republic of China
| | - Kai Wang
- Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China
| | - Xing Zhang
- Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China
| | - Guang Ji
- Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China
| | - Fenghua Li
- Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
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Boyle M, Masson S, Anstee QM. The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease. J Hepatol 2018; 68:251-267. [PMID: 29113910 DOI: 10.1016/j.jhep.2017.11.006] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 10/30/2017] [Accepted: 11/01/2017] [Indexed: 12/12/2022]
Abstract
Current medical practice artificially dichotomises a diagnosis of fatty liver disease into one of two common forms: alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Together, these account for the majority of chronic liver diseases worldwide. In recent years, there has been a dramatic increase in the prevalence of obesity and metabolic syndrome within the general population. These factors now coexist with alcohol consumption in a substantial proportion of the population. Each exposure sensitises the liver to the injurious effects of the other; an interaction that drives and potentially accelerates the genesis of liver disease. We review the epidemiological evidence and scientific literature that considers how alcohol consumption interacts with components of the metabolic syndrome to exert synergistic or supra-additive effects on the development and progression of liver disease, before discussing how these interactions may be addressed in clinical practice.
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Affiliation(s)
- Marie Boyle
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Steven Masson
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Quentin M Anstee
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
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11
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Ghosh Dastidar S, Warner JB, Warner DR, McClain CJ, Kirpich IA. Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration. Biomolecules 2018; 8:biom8010003. [PMID: 29342874 PMCID: PMC5871972 DOI: 10.3390/biom8010003] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 01/09/2018] [Accepted: 01/11/2018] [Indexed: 12/14/2022] Open
Abstract
Both chronic and acute (binge) alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD). There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH) feeding (Lieber–DeCarli liquid diet model), chronic intragastric EtOH administration (Tsukamoto–French model), and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA) model). This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s) of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.
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Affiliation(s)
- Shubha Ghosh Dastidar
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
| | - Jeffrey B Warner
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
| | - Dennis R Warner
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
| | - Craig J McClain
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
- Robley Rex Veterans Medical Center, Louisville, KY 40202, USA.
- University of Louisville Alcohol Research Center and Hepatobiology & Toxicology COBRE, University of Louisville, Louisville, KY 40202, USA.
| | - Irina A Kirpich
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
- University of Louisville Alcohol Research Center and Hepatobiology & Toxicology COBRE, University of Louisville, Louisville, KY 40202, USA.
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Gao B, Xu MJ, Bertola A, Wang H, Zhou Z, Liangpunsakul S. Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance. Gene Expr 2017; 17:173-186. [PMID: 28411363 PMCID: PMC5500917 DOI: 10.3727/105221617x695519] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and to test for therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed.
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Affiliation(s)
- Bin Gao
- *Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Ming-Jiang Xu
- *Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Adeline Bertola
- *Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
- †Université Côte d’Azur, INSERM, Centre Méditerranéen de Médecine Moléculaire, Nice, France
| | - Hua Wang
- *Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
- ‡Department of Oncology, The First Affiliated Hospital, Institute for Liver Diseases of Anhui Medical University, Hefei, P.R. China
| | - Zhou Zhou
- *Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Suthat Liangpunsakul
- §Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- ¶Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA
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Wang W, Xu MJ, Cai Y, Zhou Z, Cao H, Mukhopadhyay P, Pacher P, Zheng S, Gonzalez FJ, Gao B. Inflammation is independent of steatosis in a murine model of steatohepatitis. Hepatology 2017; 66:108-123. [PMID: 28220523 PMCID: PMC5481491 DOI: 10.1002/hep.29129] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 01/30/2017] [Accepted: 02/17/2017] [Indexed: 12/17/2022]
Abstract
UNLABELLED Obesity and alcohol consumption synergistically promote steatohepatitis, and neutrophil infiltration is believed to be associated with steatosis. However, the underlying mechanisms remain obscure. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a complex role in lipid metabolism and inflammation; therefore, the purpose of this study was to dissect its role in regulating steatosis and neutrophil infiltration in a clinically relevant mouse steatohepatitis model of 3-month high-fat diet (HFD) feeding plus a binge of ethanol (HFD-plus-binge ethanol). Hepatocyte-specific Pparg disruption reduced liver steatosis but surprisingly increased hepatic neutrophil infiltration after HFD-plus-binge ethanol. Knockout or knockdown of the PPARγ target gene, fat-specific protein 27, reduced steatosis without affecting neutrophil infiltration in this model. Moreover, hepatocyte-specific deletion of the Pparg gene, but not the fat-specific protein 27 gene, markedly up-regulated hepatic levels of the gene for chemokine (C-X-C motif) ligand 1 (Cxcl1, a chemokine for neutrophil infiltration) in HFD-plus-binge ethanol-fed mice. In vitro, deletion of the Pparg gene also highly augmented palmitic acid or tumor necrosis factor alpha induction of Cxcl1 in mouse hepatocytes. In contrast, activation of PPARγ with a PPARγ agonist attenuated Cxcl1 expression in hepatocytes. Palmitic acid also up-regulated interleukin-8 (a key chemokine for human neutrophil recruitment) expression in human hepatocytes, which was attenuated and enhanced by cotreatment with a PPARγ agonist and antagonist, respectively. Finally, acute ethanol binge markedly attenuated HFD-induced hepatic PPARγ activation, which contributed to the up-regulation of hepatic Cxcl1 expression post-HFD-plus-binge ethanol. CONCLUSION Hepatic PPARγ plays an opposing role in controlling steatosis and neutrophil infiltration, leading to dissociation between steatosis and inflammation; acute ethanol gavage attenuates hepatic PPARγ activation and subsequently up-regulates hepatic CXCL1/interleukin-8 expression, thereby exacerbating hepatic neutrophil infiltration. (Hepatology 2017;66:108-123).
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Affiliation(s)
- Wei Wang
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
- Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ming-Jiang Xu
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Yan Cai
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Zhou Zhou
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Haixia Cao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Partha Mukhopadhyay
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Pal Pacher
- Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Shusen Zheng
- Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Frank J Gonzalez
- Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
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Kema VH, Khan I, Jamal R, Vishwakarma SK, Lakki Reddy C, Parwani K, Patel F, Patel D, Khan AA, Mandal P. Protective Effects of Diallyl Sulfide Against Ethanol-Induced Injury in Rat Adipose Tissue and Primary Human Adipocytes. Alcohol Clin Exp Res 2017; 41:1078-1092. [PMID: 28414868 DOI: 10.1111/acer.13398] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 04/06/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Alcohol consumption is the fourth leading cause of death and disability worldwide. Several cellular pathways contribute to alcohol-mediated tissue injury. Adipose tissue apart from functioning as an endocrine organ secretes several hormones and cytokines known as adipokines that are known to play a significant role in alcohol-induced tissue damage. This study was designed to test the efficacy of diallyl sulfide (DAS) in regulating the alcohol-induced outcomes on adipose tissue. METHODS Male Wistar rats were fed with 36% Lieber-DeCarli liquid diet containing ethanol (EtOH) for 4 weeks. Control rats were pair-fed with isocaloric diet containing maltodextrin instead of EtOH. During the last week of feeding protocol, the EtOH-fed rat group was given 200 mg/kg body weight of DAS through diet. We also studied DAS effect on isolated human primary adipocytes. Viability of human primary adipocytes on DAS treatment was assessed by MTT assay. Malondialdehyde (MDA), a marker of oxidative stress, was measured by HPLC and the thiobarbituric acid method. Expression of inflammatory genes and lipogenic genes was studied by qRT-PCR and Western blotting. Serum inflammatory gene expression was studied by ELISA. RESULTS Our study results showed that DAS could alleviate EtOH-induced expression levels of proinflammatory and endoplasmic reticulum (ER) stress genes and improve adipose tissue mass and adipocyte morphology in male Wistar rats fed Lieber-DeCarli diet containing 6% EtOH. Further, we showed that DAS reduced the expression of lipogenic genes and improved lipid accumulation and adipocyte mass in human primary adipocytes treated with EtOH. Subsequently, we also showed that oxidative stress, as measured by the changes in MDA levels, was reduced in both male Wistar rats and human primary adipocytes treated with EtOH plus DAS. CONCLUSIONS Our study results prove that DAS is effective in ameliorating EtOH-induced damage to adipose tissue as evidenced by the reduction brought about by DAS in oxidative stress, ER stress, and proinflammatory gene expression levels. DAS treatment also regulated lipogenic gene expression levels, thereby reducing free fatty acid release. In conclusion, this study has clinical implications with respect to alcohol-induced adipose tissue injury among alcohol users.
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Affiliation(s)
| | - Imran Khan
- Department of Biological Sciences , BITS Pilani, Hyderabad, India
| | - Reshma Jamal
- Department of Biological Sciences , BITS Pilani, Hyderabad, India
| | - Sandeep Kumar Vishwakarma
- Central Laboratory for Stem Cell Research & Translational Medicine , CLRD, Deccan College of Medical Sciences, Hyderabad, India
| | - Chandrakala Lakki Reddy
- Central Laboratory for Stem Cell Research & Translational Medicine , CLRD, Deccan College of Medical Sciences, Hyderabad, India
| | - Kirti Parwani
- Department of Biological Sciences , P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Anand, Gujarat, India
| | - Farhin Patel
- Department of Biological Sciences , P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Anand, Gujarat, India
| | - Dhara Patel
- Department of Biological Sciences , P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Anand, Gujarat, India
| | - Aleem A Khan
- Central Laboratory for Stem Cell Research & Translational Medicine , CLRD, Deccan College of Medical Sciences, Hyderabad, India
| | - Palash Mandal
- Department of Biological Sciences , BITS Pilani, Hyderabad, India
- Department of Biological Sciences , P D Patel Institute of Applied Sciences, Charotar University of Science and Technology, Anand, Gujarat, India
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Kawamura Y, Arase Y, Ikeda K, Akuta N, Kobayashi M, Saitoh S, Suzuki F, Suzuki Y, Inao M, Mochida S, Kumada H. Effects of Alcohol Consumption on Hepatocarcinogenesis in Japanese Patients With Fatty Liver Disease. Clin Gastroenterol Hepatol 2016; 14:597-605. [PMID: 26707683 DOI: 10.1016/j.cgh.2015.11.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 11/30/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of ethanol consumption on hepatocarcinogenesis in patients with fatty liver disease (FLD) is not clear. We aimed to investigate the influence of alcohol consumption on hepatocarcinogenesis and determine the risk factors for hepatocellular carcinoma (HCC) in a large number of Japanese patients with FLD without viral hepatitis. METHODS This multicenter, retrospective cohort study was conducted at a specialized center for hepatology in Japan and included 9959 patients with FLD without viral hepatitis, diagnosed by ultrasonography from January 1997 through December 2011. The patients' level of ethanol consumption was divided into 4 categories: <20 g/day (n = 6671), 20-39 g/day (n = 753), 40-69 g/day (n = 1589), and ≥70 g/day (n = 946). The primary endpoint was the onset of HCC. Statistical analyses performed included the Kaplan-Meier method and Cox proportional hazard analysis. The median follow-up period was 5.4 years. RESULTS Of the study cohort, 49 cases (0.49%) developed HCC during the follow-up period. The annual incidence rate of HCC was 0.05% in patients with FLD and a daily ethanol consumption <20 g/day. Increasing levels of ethanol consumption were associated with increased annual incidence rates of HCC: 0.06% for patients with 20-39 g/day ethanol consumption (hazard ratio [HR], 1.54; 95% confidence interval [CI], 0.34-7.04), 0.16% for patients with 40-69 g/day ethanol consumption (HR, 3.49; 95% CI, 1.50-8.12), and 0.22% for patients with ≥70 g/day ethanol consumption (HR, 10.58; 95% CI, 5.06-22.13), compared with patients with ethanol consumption <20 g/day. Multivariate analysis showed that ethanol consumption ≥40 g/day was an independent risk factor for HCC: for 40-69 g/day the HR was 2.48 (95% CI, 1.01-6.05; P < .047) and for ≥70 g/day the HR was 12.61 (95% CI, 5.68-28.00; P < .001). CONCLUSIONS Based on a multicenter, retrospective analysis of almost 10,000 patients with FLD, ethanol consumption ≥40 g/day is an independent risk factor for HCC.
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Affiliation(s)
- Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Health Management Center, Toranomon Hospital, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
| | - Mie Inao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan
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Wang ZG, Dou XB, Zhou ZX, Song ZY. Adipose tissue-liver axis in alcoholic liver disease. World J Gastrointest Pathophysiol 2016; 7:17-26. [PMID: 26909225 PMCID: PMC4753183 DOI: 10.4291/wjgp.v7.i1.17] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 09/07/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage.
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Chang B, Xu MJ, Zhou Z, Cai Y, Li M, Wang W, Feng D, Bertola A, Wang H, Kunos G, Gao B. Short- or long-term high-fat diet feeding plus acute ethanol binge synergistically induce acute liver injury in mice: an important role for CXCL1. Hepatology 2015; 62:1070-85. [PMID: 26033752 PMCID: PMC4589443 DOI: 10.1002/hep.27921] [Citation(s) in RCA: 166] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 05/27/2015] [Indexed: 12/12/2022]
Abstract
UNLABELLED Obesity and alcohol consumption often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. Here, we demonstrate that feeding mice a high-fat diet (HFD) for as little as 3 days markedly exacerbated acute ethanol binge-induced liver neutrophil infiltration and injury. Feeding mice with an HFD for 3 months plus a single binge of ethanol induced much more severe steatohepatitis. Moreover, 3-day or 3-month HFD-plus-ethanol binge (3d-HFD+ethanol or 3m-HFD+ethanol) treatment markedly up-regulated the hepatic expression of several chemokines, including chemokine (C-X-C motif) ligand 1 (Cxcl1), which showed the highest fold (approximately 20-fold and 35-fold, respectively) induction. Serum CXCL1 protein levels were also markedly elevated after the HFD+ethanol treatment. Blockade of CXCL1 with a CXCL1 neutralizing antibody or genetic deletion of the Cxcl1 gene reduced the HFD+ethanol-induced hepatic neutrophil infiltration and injury, whereas overexpression of Cxcl1 exacerbated steatohepatitis in HFD-fed mice. Furthermore, expression of Cxcl1 messenger RNA was up-regulated in hepatocytes, hepatic stellate cells, and endothelial cells isolated from HFD+ethanol-fed mice compared to mice that were only given the HFD, with the highest fold induction observed in hepatocytes. In vitro stimulation of hepatocytes with palmitic acid up-regulated the expression of Cxcl1 messenger RNA, and this up-regulation was attenuated after treatment with an inhibitor of extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, or nuclear factor κB. In addition, hepatic or serum levels of free fatty acids were higher in HFD+ethanol-fed mice than in the control groups. CONCLUSION An HFD combined with acute ethanol consumption synergistically induces acute liver inflammation and injury through the elevation of hepatic or serum free fatty acids and subsequent up-regulation of hepatic CXCL1 expression and promotion of hepatic neutrophil infiltration.
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Affiliation(s)
- Binxia Chang
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA,Diagnosis and Treatment Center for Non-Infectious Liver Diseases, Institute of Alcoholic Liver Disease, Beijing 302 Hospital, Beijing
| | - Ming-Jiang Xu
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Zhou Zhou
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Yan Cai
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Man Li
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Wei Wang
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Dechun Feng
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Adeline Bertola
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Hua Wang
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - George Kunos
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA
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Lau K, Baumeister SE, Lieb W, Meffert PJ, Lerch MM, Mayerle J, Völzke H. The combined effects of alcohol consumption and body mass index on hepatic steatosis in a general population sample of European men and women. Aliment Pharmacol Ther 2015; 41:467-76. [PMID: 25588768 DOI: 10.1111/apt.13067] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 07/21/2014] [Accepted: 12/12/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND Research on the association between alcohol consumption and hepatic steatosis revealed conflictive results. AIM To investigate the associations between average daily alcohol consumption and binge drinking with hepatic steatosis, and to analyse combined effects of average daily alcohol consumption and binge drinking with body mass index (BMI) on hepatic steatosis. METHODS Data from the population-based Study of Health in Pomerania (SHIP) conducted in north-east Germany comprising 4009 adults were used. Alcohol consumption was assessed by self-report. Serum carbohydrate-deficient transferrin (CDT) was analysed as biomarker for alcohol consumption. Hepatic steatosis was diagnosed by ultrasonography. RESULTS Analyses revealed a dose-response relationship between average daily alcohol consumption and hepatic steatosis in men starting with a consumption of 20 g of alcohol per day [adjusted odds ratio (OR) compared to abstainers 1.53; 95% confidence interval (CI) 1.15-2.05]. Using CDT as alternative exposure variable confirmed these results. Binge drinking was associated with hepatic steatosis in men (adjusted OR of binge drinkers compared to nonbinge drinkers 1.36, 95% CI 1.06-1.74). The likelihood of having hepatic steatosis increased in men and women with increasing levels of average daily alcohol consumption in combination with overweight or obesity. Similarly, binge drinking in combination with overweight or obesity enhanced the likelihood of having hepatic steatosis. CONCLUSIONS Overweight or obesity substantially enhanced the effect of high levels of average daily alcohol consumption and binge drinking on hepatic steatosis in the present study population. This finding underlines the necessity to screen for multiple risk factors in the prevention of hepatic steatosis.
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Affiliation(s)
- K Lau
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf and Schön Clinics Hamburg Eilbek, Hamburg, Germany
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Elrazek AEMAA, Elbanna AEM, Bilasy SE. Medical management of patients after bariatric surgery: Principles and guidelines. World J Gastrointest Surg 2014; 6:220-228. [PMID: 25429323 PMCID: PMC4241489 DOI: 10.4240/wjgs.v6.i11.220] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 09/06/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index (BMI) is associated with increased rate of death from several causes, among them cardiovascular disease; which is particularly true for those with morbid obesity. Being overweight was also associated with decreased survival in several studies. Unfortunately, obese subjects are often exposed to public disapproval because of their fatness which significantly affects their psychosocial behavior. All obese patients (BMI ≥ 30 kg/m2) should receive counseling on diet, lifestyle, exercise and goals for weight management. Individuals with BMI ≥ 40 kg/m2 and those with BMI > 35 kg/m2 with obesity-related comorbidities; who failed diet, exercise, and drug therapy, should be considered for bariatric surgery. In current review article, we will shed light on important medical principles that each surgeon/gastroenterologist needs to know about bariatric surgical procedure, with special concern to the early post operative period. Additionally, we will explain the common complications that usually follow bariatric surgery and elucidate medical guidelines in their management. For the first 24 h after the bariatric surgery, the postoperative priorities include pain management, leakage, nausea and vomiting, intravenous fluid management, pulmonary hygiene, and ambulation. Patients maintain a low calorie liquid diet for the first few postoperative days that is gradually changed to soft solid food diet within two or three weeks following the bariatric surgery. Later, patients should be monitored for postoperative complications. Hypertension, diabetes, dumping syndrome, gastrointestinal and psychosomatic disorders are among the most important medical conditions discussed in this review.
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20
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Dou X, Xia Y, Chen J, Qian Y, Li S, Zhang X, Song Z. Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease. Br J Pharmacol 2014; 171:4073-86. [PMID: 24819676 DOI: 10.1111/bph.12765] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 04/22/2014] [Accepted: 04/25/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND PURPOSE Overactive lipolysis in adipose tissue contributes to the pathogenesis of alcoholic liver disease (ALD); however, the mechanisms involved have not been elucidated. We previously reported that chronic alcohol consumption produces a hypomethylation state in adipose tissue. In this study we investigated the role of hypomethylation in adipose tissue in alcohol-induced lipolysis and whether its correction contributes to the well-established hepatoprotective effect of betaine in ALD. EXPERIMENTAL APPROACH Male C57BL/6 mice were divided into four groups and started on one of four treatments for 5 weeks: isocaloric pair-fed (PF), alcohol-fed (AF), PF supplemented with betaine (BT/AF) and AF supplemented with betaine (BT/AF). Betaine, 0.5% (w v(-1) ), was added to the liquid diet. Both primary adipocytes and mature 3T3-L1 adipocytes were exposed to demethylation reagents and their lipolytic responses determined. KEY RESULTS Betaine alleviated alcohol-induced pathological changes in the liver and rectified the impaired methylation status in adipose tissue, concomitant with attenuating lipolysis. In adipocytes, inducing hypomethylation activated lipolysis through a mechanism involving suppression of protein phosphatase 2A (PP2A), due to hypomethylation of its catalytic subunit, leading to increased activation of hormone-sensitive lipase (HSL). In line with in vitro observations, reduced PP2A catalytic subunit methylation and activity, and enhanced HSL activation, were observed in adipose tissue of alcohol-fed mice. Betaine attenuated this alcohol-induced PP2A suppression and HSL activation. CONCLUSIONS AND IMPLICATIONS In adipose tissue, a hypomethylation state contributes to its alcohol-induced dysfunction and an improvement in its function may contribute to the hepatoprotective effects of betaine in ALD.
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Affiliation(s)
- Xiaobing Dou
- College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA
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Utilisation de l’élastométrie hépatique comme outil de dépistage de la fibrose hépatique dans un service d’addictologie. Presse Med 2014; 43:e17-31. [DOI: 10.1016/j.lpm.2013.07.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Revised: 07/09/2013] [Accepted: 07/15/2013] [Indexed: 12/11/2022] Open
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Cibeira GH, Muller C, Lazzaretti R, Nader GA, Caleffi M. Consumo de bebida alcoólica, fatores socioeconômicos e excesso de peso: um estudo transversal no sul do Brasil. CIENCIA & SAUDE COLETIVA 2013; 18:3577-84. [DOI: 10.1590/s1413-81232013001200014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Accepted: 06/09/2012] [Indexed: 11/22/2022] Open
Abstract
O objetivo do estudo foi investigar o consumo de álcool e verificar sua associação com escolaridade, renda e excesso de peso em uma amostra de mulheres. Trata-se de um estudo transversal com 317 mulheres. Aplicou-se um questionário padronizado e pré-codificado para determinar a quantidade, a frequência e o tipo de bebida alcoólica consumida. As mulheres foram classificadas em dois grandes grupos, conforme a quantidade de bebida consumida. O primeiro grupo "Consumo de Álcool", formado por duas subcategorias: (1) mulheres que bebiam no mínimo 10g/dia de etanol; (2) mulheres que referiram não consumir 10g/dia de etanol e as que beberam em algum período da vida ou previamente, mas que o deixaram de fazer. O segundo grupo, "Contato com Álcool", foi composto por três subcategorias: (1) bebedoras (mulheres que bebiam no mínimo 10g/dia de etanol), (2) ex-bebedoras (já beberam regularmente, mas deixaram de consumir a bebida) e (3) não bebedoras. Das investigadas, 30% eram bebedoras e 36,6% se declararam ex-bebedoras. Tinham sobrepeso 39,4% das participantes e 34,3% eram obesas. As investigadas com maior grau de instrução consumiam maior quantidade de álcool, quando comparadas às mulheres com menor escolaridade (analfabetas) que consumam menos (p = 0,010).
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Lee HI, McGregor RA, Choi MS, Seo KI, Jung UJ, Yeo J, Kim MJ, Lee MK. Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK. Life Sci 2013; 93:693-699. [PMID: 24063989 DOI: 10.1016/j.lfs.2013.09.014] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 09/04/2013] [Accepted: 09/11/2013] [Indexed: 12/20/2022]
Abstract
AIMS This study investigated the hepatoprotective effects of low doses of curcumin against liver damage induced by chronic alcohol intake and a high-fat diet. We also examined several potential underlying mechanisms including action on alcohol metabolism, antioxidant activity, AMPK level and lipid metabolism. MAIN METHOD Alcohol (25% v/v, 5 g/kg body weight) was orally administered once a day for 6 weeks to mice fed a high-fat diet with or without two different doses of curcumin (0.02% and 0.05%, wt/wt). KEY FINDINGS Curcumin significantly decreased the plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities (p<0.05) and prevented hepatic steatosis compared with the alcohol control group. Curcumin significantly reversed the alcohol-induced inhibition of the alcohol dehydrogenase, aldehyde dehydrogenase 2 and antioxidant enzyme activities as well as the activation of cytochrome P4502E1 and promotion of lipid peroxidation (p<0.05). Curcumin significantly increased the hepatic total AMPK protein level and concomitantly suppressed the fatty acid synthase and phosphatidate phosphohydrolase activities compared with the alcohol control group (p<0.05). Furthermore, curcumin significantly lowered the plasma leptin, free fatty acids and triglycerides levels and hepatic lipid levels (p<0.05). SIGNIFICANCE These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating the alcohol metabolic enzyme activity, the antioxidant activity and the lipid metabolism. Therefore, curcumin may provide a promising natural therapeutic strategy against liver disease.
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Affiliation(s)
- Hae-In Lee
- Department of Food and Nutrition, Sunchon National University, Suncheon 540-742, Republic of Korea
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Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol 2013; 28 Suppl 1:11-17. [PMID: 23855290 DOI: 10.1111/jgh.12036] [Citation(s) in RCA: 209] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2013] [Indexed: 12/12/2022]
Abstract
The prevalence of patients presenting with fatty liver disease (FLD) in China has approximately doubled over the past two decades. At present, FLD, which is typically diagnosed by imaging, is highly prevalent (≈ 27% urban population) in China and is mainly related to obesity and metabolic syndrome (MetS). However, the percentage of alcoholic liver disease (ALD) among patients with chronic liver diseases in clinic is increasing as well, and a synergetic effect exists between heavy alcohol drinking and obesity in ALD. Prevalence figures reveal regional variations, with a median prevalence of ALD and nonalcoholic FLD (NAFLD) of 4.5% and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although the prevalence increases to 68.2% among obese children. With the increasing pandemic of obesity and MetS in the general population, China is likely to harbor an increasing reservoir of patients with FLD. The risk factors for FLD resemble to those of Caucasian counterparts, but the ethnic-specific definitions of obesity and MetS are more useful in assessment of Chinese people. Therefore, FLD/NAFLD has become a most common chronic liver disease in China. Public health interventions are needed to halt the worldwide trend of obesity and alcohol abuse to ameliorate liver injury and to improve metabolic health.
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Affiliation(s)
- Jian-Gao Fan
- Department of Gastroenterology, Shanghai Key Laboratory of Children's Digestion and Nutrition, Xin-Hua Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
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Everitt H, Hu M, Ajmo JM, Rogers CQ, Liang X, Zhang R, Yin H, Choi A, Bennett ES, You M. Ethanol administration exacerbates the abnormalities in hepatic lipid oxidation in genetically obese mice. Am J Physiol Gastrointest Liver Physiol 2013; 304:G38-47. [PMID: 23139221 PMCID: PMC3543633 DOI: 10.1152/ajpgi.00309.2012] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Alcohol consumption synergistically increases the risk and severity of liver damage in obese patients. To gain insight into cellular or molecular mechanisms underlying the development of fatty liver caused by ethanol-obesity synergism, we have carried out animal experiments that examine the effects of ethanol administration in genetically obese mice. Lean wild-type (WT) and obese (ob/ob) mice were subjected to ethanol feeding for 4 wk using a modified Lieber-DeCarli diet. After ethanol feeding, the ob/ob mice displayed much more pronounced changes in terms of liver steatosis and elevated plasma levels of alanine aminotransferase and aspartate aminotransferase, indicators of liver injury, compared with control mice. Mechanistic studies showed that ethanol feeding augmented the impairment of hepatic sirtuin 1 (SIRT1)-AMP-activated kinase (AMPK) signaling in the ob/ob mice. Moreover, the impairment of SIRT1-AMPK signaling was closely associated with altered hepatic functional activity of peroxisome proliferator-activated receptor γ coactivator-α and lipin-1, two vital downstream lipid regulators, which ultimately contributed to aggravated fatty liver observed in ethanol-fed ob/ob mice. Taken together, our novel findings suggest that ethanol administration to obese mice exacerbates fatty liver via impairment of the hepatic lipid metabolism pathways mediated largely by a central signaling system, the SIRT1-AMPK axis.
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Affiliation(s)
- Hannah Everitt
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Ming Hu
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Joanne M. Ajmo
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Christopher Q. Rogers
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Xiaomei Liang
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Ray Zhang
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Huquan Yin
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Alison Choi
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Eric S. Bennett
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
| | - Min You
- Departments of Molecular Pharmacology and Physiology, University of South Florida Health Sciences Center, Tampa, Florida
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Bruha R, Dvorak K, Petrtyl J. Alcoholic liver disease. World J Hepatol 2012; 4:81-90. [PMID: 22489260 PMCID: PMC3321494 DOI: 10.4254/wjh.v4.i3.81] [Citation(s) in RCA: 126] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2011] [Revised: 09/07/2011] [Accepted: 03/17/2012] [Indexed: 02/06/2023] Open
Abstract
Alcohol use disorders affect millions of individuals worldwide. Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs. Alcoholic liver disease (ALD) may take the form of acute involvement (alcoholic hepatitis) or chronic liver disease (steatosis, steatohepatitis, fibrosis and cirrhosis). The severity and prognosis of alcohol-induced liver disease depends on the amount, pattern and duration of alcohol consumption, as well as on the presence of liver inflammation, diet, nutritional status and genetic predisposition of an individual. While steatosis is an almost completely benign disease, liver cirrhosis is associated with marked morbidity, mortality and life expectancy shortening. The median survival of patients with advanced cirrhosis is 1-2 years. Severe acute alcoholic hepatitis (AH) is associated with mortality as high as 50%. It has been managed with corticoids, pentoxifylline and enteral nutrition, although evidence based data are still conflicting. Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH. Absolute abstinence is a basic condition for any treatment of acute or chronic ALD, the other therapeutical procedure being of a supportive nature and questionable significance. Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alcohol dependent patients. Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation, which leads to a markedly prolonged life expectancy. The crucial step in ALD prevention is in the prevention of alcohol abuse, whereas the prevention of liver injury in active alcohol abusers is not clinically applicable.
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Affiliation(s)
- Radan Bruha
- Radan Bruha, 4th Department of Internal Medicine, General Teaching Hospital, First Faculty of Medicine, Charles University, 12808 Prague, Czech Republic
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Hart CL, Morrison DS, Batty GD, Mitchell RJ, Davey Smith G. Effect of body mass index and alcohol consumption on liver disease: analysis of data from two prospective cohort studies. BMJ 2010; 340:c1240. [PMID: 20223873 PMCID: PMC2837144 DOI: 10.1136/bmj.c1240] [Citation(s) in RCA: 308] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/24/2010] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To investigate whether alcohol consumption and raised body mass index (BMI) act together to increase risk of liver disease. DESIGN Analysis of data from prospective cohort studies. SETTING Scotland. PARTICIPANTS Data were from two of the Midspan prospective cohort studies (9559 men): "Main" study 1965-8, participants from workplaces across central belt of Scotland, population of island of Tiree, and mainland relatives, and "Collaborative" study, 1970-3, participants from 27 workplaces in Glasgow, Clydebank, and Grangemouth. Follow-up was to 31 December 2007 (median 29 years, range 0.13-42). We divided participants into nine groups based on measures of body mass index (BMI) (underweight/normal weight <25, overweight 25 to <30, and obese >or=30) and alcohol consumption (none, 1-14, and >or=15 units per week). MAIN OUTCOME MEASURES Liver disease morbidity and mortality. RESULTS 80 (0.8%) men died with liver disease as the main cause and 146 (1.5%) with liver disease as any cause. In the Collaborative study, 196 men (3.3%) had liver disease defined by a death, admission, or cancer registration. BMI and alcohol consumption were strongly associated with liver disease mortality in analyses adjusted for other confounders (P=0.001 and P<0.0001 respectively). Drinkers of 15 or more units per week in any BMI category and obese drinkers had raised relative rates for all definitions of liver disease, compared with underweight/normal weight non-drinkers. Drinkers of 15 or more units per week had adjusted relative rates for liver disease mortality of 3.16 (95% confidence interval 1.28 to 7.8) for underweight/normal weight men, 7.01 (3.02 to 16.3) for overweight, and 18.9 (6.84 to 52.4) for obese men. The relative rate for obese men who consumed 1-14 units per week was 5.3 (1.36 to 20.7). The relative excess risk due to interaction between BMI and alcohol consumption was 5.58 (1.09 to 10.1); synergy index=2.89 (1.29 to 6.47). CONCLUSIONS Raised BMI and alcohol consumption are both related to liver disease, with evidence of a supra-additive interaction between the two. The occurrence of both factors in the same populations should inform health promotion and public health policies.
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Affiliation(s)
- Carole L Hart
- Public Health and Health Policy, Division of Community Based Sciences, Faculty of Medicine, University of Glasgow, Glasgow G12 8RZ.
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