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Kang J, Park SH, Khanam M, Park SB, Shin S, Seo W. Impact of binge drinking on alcoholic liver disease. Arch Pharm Res 2025; 48:212-223. [PMID: 40035998 DOI: 10.1007/s12272-025-01537-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 02/13/2025] [Indexed: 03/06/2025]
Abstract
Numerous studies have examined the pathophysiological changes induced by chronic alcohol (ethanol) consumption and the underlying mechanisms, while much less attention has been devoted to understanding the health impacts of binge drinking. Binge drinking is defined as the excessive consumption of alcohol within a single drinking episode, and is the typical consumption pattern among young people in Western countries. While most young binge drinkers are not clinically alcohol dependent, binge drinking has emerged as a significant social and public health concern. The circulating alcohol consumed during binge episodes permeates cellular membranes throughout the body, exerting profound effects on multiple organs, and signaling pathways. Regular binge drinking eventually induces hepatic steatosis (fatty liver), initiates acute inflammation, and accelerates neutrophil infiltration, de novo lipogenesis, adipocyte death/lipolysis, and the production of nonoxidative alcohol metabolites, processes that synergize to damage liver tissue and impair liver function. Metabolic abnormalities such as diabetes and obesity can also exacerbate the progression of alcohol-related liver disease among binge drinkers. Several animal models have been developed to evaluate the pathophysiological changes resulting from binge drinking; however, the pathogenesis of binge drinking is not fully understood due to differences in alcohol metabolism between animal models and humans. Thus, given the high prevalence and severe health implications of binge drinking, there is an urgent need for comprehensive experimental and clinical investigations to unravel the associated pathophysiological changes. This review summarizes recent research findings on the impact of binge drinking, specifically focusing on its contributions to alcoholic liver injury.
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Affiliation(s)
- Jisoo Kang
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Seol Hee Park
- Department of Companion Animal Health, Hanyang Women's University, Seoul, 04763, Republic of Korea
| | - Mushira Khanam
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Seo Bhin Park
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Sumin Shin
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea
| | - Wonhyo Seo
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea.
- Graduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul, 03760, Republic of Korea.
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Yang K, Ryu T, Chung BS. Psyllium fiber improves hangovers and inflammatory liver injury by inhibiting intestinal drinking. Front Pharmacol 2024; 15:1378653. [PMID: 39005935 PMCID: PMC11239518 DOI: 10.3389/fphar.2024.1378653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 06/11/2024] [Indexed: 07/16/2024] Open
Abstract
Introduction: Excessive alcohol intake often results in hangovers and inflammatory liver damage, posing a significant health concern. Current treatment options for hangovers are still insufficient, highlighting the urgent need for new therapeutic approaches. Psyllium fiber (PF) is well-known for its gastrointestinal benefits, but its effect on hangovers is less explored. Methods: We utilized a mouse model with a single binge drinking (4 g/kg) to induce hangover and inflammatory liver injury. Intestine and liver injury were serologically and histologically estimated. Hangover symptoms were assessed using cylinder and footprint tests to objectively quantify hangover symptoms in mice. Results: Binge drinking significantly activated alcohol-metabolizing enzymes in the small intestine and liver, leading to inflammatory damage. Concurrently, there was a rise in alcohol metabolites such as acetaldehyde and acetone, which exhibited a positive correlation with hangover symptoms in mice. Interestingly, the oral administration of PF (100 mg/kg) alongside alcohol consumption significantly reduced the activity of these enzymes and lowered the levels of alcohol metabolites. Mice treated with PF exhibited a considerable improvement in hangover symptoms and a reduction in hepatic inflammation, compared to control groups. Furthermore, in vitro experiments using HepG2 cell lines and semipermeable membranes demonstrated that PF effectively inhibits alcohol absorption into the body. Discussion: In conclusion, PF demonstrates a potential protective effect against alcohol-induced hangover and liver injury by inhibiting the absorption of alcohol and lowering hangover-related alcohol metabolites. This study suggests that PF could serve as an effective therapeutic option for mitigating the adverse effects of excessive alcohol consumption.
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Affiliation(s)
- Keungmo Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Tom Ryu
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Republic of Korea
| | - Beom Sun Chung
- Department of Anatomy, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
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Romero-Gómez M, Arab JP, Oliveira CP, Hernández M, Arrese M, Cortez-Pinto H, Bataller R. Is There a Safe Alcohol Consumption Limit for the General Population and in Patients with Liver Disease? Semin Liver Dis 2024; 44:69-78. [PMID: 38574752 DOI: 10.1055/s-0044-1785228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.
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Affiliation(s)
- Manuel Romero-Gómez
- UCM Digestive Diseases and CIBERehd, Institute of Biomedicine of Seville (HUVR/CSIC/US), Virgen del Rocío University Hospital, University of Seville, Seville, Spain
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Claudia P Oliveira
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Faculdade de Medicina, Universidade de São Paulo, Hospital das Clínicas HCFMUSP, Sao Paulo, Brazil
| | - María Hernández
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Marco Arrese
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro de Envejecimiento y Regeneración, Santiago, Chile
| | - Helena Cortez-Pinto
- Clínica Universitaria de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - Ramón Bataller
- Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain
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Testino G, Pellicano R, Caputo F. Alcohol consumption, alcohol use disorder and organ transplantation. Minerva Gastroenterol (Torino) 2023; 69:553-565. [PMID: 36222679 DOI: 10.23736/s2724-5985.22.03281-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
In the present experience we have evaluated the link alcohol consumption/alcohol use disorder (AUD) and organ transplantation (OT) in order to provide adequate suggestions. The data used for the preparation of these recommendations are based on a detailed analysis of the scientific literature published before August 31, 2022 (Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted the guidelines/position papers of the scientific societies. With regard to the liver transplantation, there are position papers/guidelines that clearly define indications and contraindications for including the AUD patient in the transplant list. One of the major difficulties in this area is psychosocial assessment which can be influenced by stigma. To solve this problem, it is necessary to use objective tools. However, this assessment should be carried out after providing the patient and family adequate tools to be able to create or recreate reliable socio-family support. This behavior should also be used in the case of other OTs. For the latter, however, adequate guidelines must be created which at the moment do not exist or if there are, as in the case of heart transplantation, they are not sufficient. Even in the absence of obvious alcohol addiction, it is recommended to use alcohol use disorder identification test and to include the addiction specialist in the multidisciplinary transplant team. Besides, providing family members with the tools necessary to better support the patient is essential. They are patients with alcohol use disorder/ possible presence of psychopathological manifestations and alcohol-related pathology (cirrhosis, cardiomyopathy, liver-kidney disfunction, etc.). A cardiovascular and oncologic surveillance post-OT is recommended. For the selection of patients to be included in the list for non-LT (heart, lung, kidney, multivisceral, etc.) it is mandatory to include the diagnosis and treatment of AUDs in the guidelines. What has already been indicated for LT may be useful. Timing of alcoholic abstention in relation to clinical severity, optimal psychosocial activity, anticraving therapy in relation to the type of underlying disease and clinical severity. Close collaboration between scientific societies is required to better manage AUD patients who need OT.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, ASL3 Liguria, IRCCS San Martino University Hospital, Genoa, Italy -
- Centro Studi Mutual-self-help, Community Programs and Caregiver Training, ASL3 Liguria, Genoa, Italy -
| | | | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, University of Ferrara, Ferrara, Italy
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Testino G, Pellicano R. Corrected and republished from: Metabolic associated liver disease. Panminerva Med 2023; 65:391-399. [PMID: 37750860 DOI: 10.23736/s0031-0808.23.04850-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 c/o Polyclinic San Martino Hospital, Genoa, Italy -
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette-SGAS Hospital, Turin, Italy, Corrected and republished from: Panminerva Medica 2022 December
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Marot A, Henrion J, Knebel JF, Trépo E, Moreno C, Deltenre P. A model for individualized prediction of liver-related death in outpatients with alcohol-associated cirrhosis. Hepatol Commun 2023; 7:e0229. [PMID: 37655969 PMCID: PMC10476762 DOI: 10.1097/hc9.0000000000000229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 06/15/2023] [Indexed: 09/02/2023] Open
Abstract
INTRODUCTION In alcohol-associated cirrhosis, an accurate estimate of the risk of death is essential for patient care. We developed individualized prediction charts for 5-year liver-related mortality among outpatients with alcohol-associated cirrhosis that take into account the impact of abstinence. METHODS We collected data on outpatients with alcohol-associated cirrhosis in a prospective registry. The model was derived, internally and externally validated, and compared with the Child-Pugh and the Model For End-Stage Liver Disease (MELD) scores. RESULTS A total of 527 and 127 patients were included in the derivation and validation data sets, respectively. A model was developed based on the 3 variables independently associated with liver-related mortality in multivariate analyses (age, Child-Pugh score, and abstinence). In the derivation data set, the model combining age, Child-Pugh score, and abstinence outperformed the Child-Pugh and the MELD scores. In the validation data set, the Brier score was lower for the model (0.166) compared with the Child-Pugh score (0.196, p = 0.008) and numerically lower compared with the MELD score (0.190) (p = 0.06). The model had the greatest AUC (0.77; 95% CI 0.68-0.85) compared with the Child-Pugh score (AUC = 0.66; 95% CI 0.56-0.76, p = 0.01) and was numerically higher than that of the MELD score (AUC = 0.66; 95% CI 0.56-0.78, p = 0.06). Also, the Akaike and Bayesian information criterion scores were lower for the model (2163; 2172) compared with the Child-Pugh (2213; 2216) or the MELD score (2205; 2208). CONCLUSION A model combining age, Child-Pugh score, and abstinence accurately predicts liver-related death at 5 years among outpatients with alcohol-associated cirrhosis. In this study, the model outperformed the Child-Pugh and the MELD scores, although the AUC and the Brier score of the model were not statically different from the MELD score in the validation data set.
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Affiliation(s)
- Astrid Marot
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - Jean Henrion
- Department of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Jean-François Knebel
- Division of Radiology, Centre d’Imagerie Biomédicale (CIBM), Hôpital Nestlé, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
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Torp N, Israelsen M, Nielsen MJ, Åstrand CP, Juhl P, Johansen S, Hansen CD, Madsen B, Villesen IF, Leeming DJ, Thiele M, Hansen T, Karsdal M, Krag A. Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO-C3). Liver Int 2022; 42:92-101. [PMID: 34845832 DOI: 10.1111/liv.15120] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 10/27/2021] [Accepted: 11/03/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Binge drinking is associated with an increased risk of liver disease. Morbidity and mortality of alcohol-related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, the acute effects of binge drinking on ECM turnover are unknown. We aimed to investigate the effects on hepatic ECM turnover following a binge drinking episode. METHODS We performed a pathophysiological intervention study with 15 non-alcoholic fatty liver disease (NAFLD) patients, 15 ALD patients and 10 healthy controls. We used 40% ethanol in 9 mg/mL NaCl administered through a nasogastric tube to simulate binge drinking. Hepatic vein catheterisation allowed simultaneous hepatic- and systemic vein sampling. Markers of ECM formation and degradation were measured with competitive ELISA. RESULTS The interstitial matrix formation marker PRO-C3 increased by 1.2 ng/mL (10%, P < .001) 24 hours after binge drinking. In participants with existing liver fibrosis determined by elevated baseline PRO-C3, hepatic levels increased by 0.09 ng/mL (95% CI: 0.03-0.15, P = .005) while systemic PRO-C3 decreased 0.11 ng/mL (95% CI: -0.15 to -0.06, P < .001) in 3 hours. PRO-C8 increased by 30% (+0.9 ng/mL, P = .014) in liver-diseased patients with F0-F1 but not in any other group. Twenty-four-hour changes in systemic C3M and PRO-C3 were not associated (P = .911). CONCLUSIONS Binge drinking induced an acute burst of PRO-C3 in healthy individuals and patients with liver disease. Markers of ECM degradation were not correlated to markers of ECM formation, suggesting that even a single episode of binge drinking promotes excessive hepatic fibrogenesis.
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Affiliation(s)
- Nikolaj Torp
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Mads Israelsen
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | | | - Claus P Åstrand
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Pernille Juhl
- Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Stine Johansen
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Camilla D Hansen
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Bjørn Madsen
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Ida F Villesen
- Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark
| | | | - Maja Thiele
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Morten Karsdal
- Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark.,Department of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
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8
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Ferreira ML, Sartes LMA. Effectiveness of Brief Intervention for Alcohol Use: a Randomized Trial. Int J Ment Health Addict 2021. [DOI: 10.1007/s11469-021-00709-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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9
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Im PK, Millwood IY, Kartsonaki C, Guo Y, Chen Y, Turnbull I, Yu C, Du H, Pei P, Lv J, Walters RG, Li L, Yang L, Chen Z. Alcohol drinking and risks of liver cancer and non-neoplastic chronic liver diseases in China: a 10-year prospective study of 0.5 million adults. BMC Med 2021; 19:216. [PMID: 34530818 PMCID: PMC8447782 DOI: 10.1186/s12916-021-02079-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 07/28/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Alcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations. METHODS The prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30-79 years recruited from ten areas during 2004-2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years' follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease. RESULTS Overall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23-1.69) for liver cancer (n = 547), 1.83 (1.60-2.09) for liver cirrhosis (n = 388), 2.01 (1.77-2.28) for ALD (n = 200), 1.71 (1.35-2.16) for NAFLD (n = 198), and 1.52 (1.40-1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40-3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01-1.72), liver cirrhosis (1.37, 1.02-1.85), and ALD (1.60, 1.09-2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers. CONCLUSIONS In Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.
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Affiliation(s)
- Pek Kei Im
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Iona Y Millwood
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK.
| | - Christiana Kartsonaki
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Yu Guo
- Chinese Academy of Medical Sciences, Beijing, China
| | - Yiping Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Iain Turnbull
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Huaidong Du
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Pei Pei
- Chinese Academy of Medical Sciences, Beijing, China
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Robin G Walters
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Ling Yang
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK.
| | - Zhengming Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, OX3 7LF, UK
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10
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Testino G, Fagoonee S, Caputo F, Pellicano R. The early identification of alcohol use disorders and liver injury: proposal for a diagnostic algorithm. Panminerva Med 2021; 63:361-367. [PMID: 33494566 DOI: 10.23736/s0031-0808.21.04272-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Alcohol use disorders (AUDs) cause 80% of hepatotoxic-related deaths, and approximately 40% of cases of cirrhosis is due to alcohol. The relative risk of developing cirrhosis increases significantly for doses above 60 g/day for men and 20 g/day for women over a period of 10 years. Hence, there is a great opportunity to early detect both AUDs and liver disease, optimizing their management. Such strategy allows patients to be included in a detoxification program in order to achieve total abstinence. Nevertheless, it is crucial to highlight that a great part of patients hospitalized for the first time with cirrhosis or liver failure are not aware to have AUDs. This implies that most of them are diagnosed at an advanced stage. This is more serious considering that about 5% of cirrhotic patients develop hepatocellular carcinoma (HCC). Consequently, this malignancy is diagnosed late. Early detection of fibrosis, is a crucial step in patients with liver disease due to AUDs, influencing treatment and prognosis. Liver biopsy represents the gold standard to diagnose and to stage fibrosis. However, the main limitations of this approach are its invasiveness and its reduced representation of the histological picture. For these reasons, noninvasive methods have been introduced in the latest decade, being the main one elastography, which measure liver stiffness, a parameter directly correlated to liver fibrosis. In this review, we propose an algorithm for early identification of AUDs and liver disease, permitting to early identify HCC and to treat with alcohological programs these patients.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, IRCCS Ospedale Policlinico San Martino, ASL3, Genoa, Italy -
- Italian Society on Alcohol (SIA), Bologna, Italy -
| | - Sharmila Fagoonee
- Molecular Biotechnology Center, National Research Council, Institute of Biostructure and Bioimaging, Turin, Italy
| | - Fabio Caputo
- Italian Society on Alcohol (SIA), Bologna, Italy
- Unit of Internal Medicine, Cento Hospital, University of Ferrara, Ferrara, Italy
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11
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Zhang Y, Fan Y, He W, Han Y, Bao H, Yang R, Wang B, Kong D, Wang H. Persistent deficiency of mucosa-associated invariant T (MAIT) cells during alcohol-related liver disease. Cell Biosci 2021; 11:148. [PMID: 34321090 PMCID: PMC8320031 DOI: 10.1186/s13578-021-00664-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 07/20/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear. RESULTS In this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8. CONCLUSIONS Our findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.
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Affiliation(s)
- Yujue Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Yuanyuan Fan
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China
| | - Wei He
- School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Yi Han
- Department of Gastroenterology, Fuyang Hospital of Anhui Medical University, Fuyang, 236000, Anhui, P.R. China
| | - Huarui Bao
- Department of Emergency, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Renjun Yang
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Bingbing Wang
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Derun Kong
- Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. .,Department of Gastroenterology, Fuyang Hospital of Anhui Medical University, Fuyang, 236000, Anhui, P.R. China.
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China. .,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, Anhui, China.
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12
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Furtmann JK, Sichtermann T, Oros-Peusquens AM, Dekeyzer S, Shah NJ, Wiesmann M, Nikoubashman O. MRI Analysis Of the Water Content Change In the Brain During Acute Ethanol Consumption Via Quantitative Water Mapping. Alcohol Alcohol 2021; 57:429-436. [PMID: 34002208 DOI: 10.1093/alcalc/agab026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 03/15/2021] [Accepted: 03/16/2021] [Indexed: 11/13/2022] Open
Abstract
AIMS Alcohol consumption influences the water balance in the brain. While the impact of chronic alcohol misuse on cerebral water content has been the subject of several studies, less is known about the effects of acute alcohol misuse, with contradictory results in the literature. Therefore, we investigated the effects of acute alcohol intoxication on cerebral water content using a precise quantitative magnetic resonance imaging (MRI) sequence. METHODS In a prospective study, we measured cerebral water content in 20 healthy volunteers before alcohol consumption and after reaching a breath alcohol concentration of 1 ‰. A quantitative MRI water mapping sequence was conducted on a clinical 3 T system. Non-alcoholic fluid input and output were documented and accounted for. Water content was assessed for whole brain, grey and white matter and more specifically for regions known to be affected by acute or chronic alcohol misuse (occipital and frontal lobes, thalamus and pons). Changes in the volume of grey and white matter as well as the whole brain were examined. RESULTS Quantitative cerebral water content before and after acute alcohol consumption did not differ significantly (P ≥ 0.07), with changes often being within the range of measurement accuracy. Whole brain, white and grey matter volume did not change significantly (P ≥ 0.12). CONCLUSION The results of our study show no significant water content or volume change in the brain after recent alcohol intake in healthy volunteers. This accounts for the whole brain, grey and white matter, occipital and frontal lobes, thalamus and pons.
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Affiliation(s)
- Johanna K Furtmann
- Department of Diagnostic and Interventional Neuroradiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany
| | - Thorsten Sichtermann
- Department of Diagnostic and Interventional Neuroradiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany
| | - Ana-Maria Oros-Peusquens
- Institute of Neurosciences and Medicine 4 (INM-4), Forschungszentrum Jülich, 52425 Jülich, Germany
| | - Sven Dekeyzer
- Department of Radiology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
| | - Nadim J Shah
- Institute of Neurosciences and Medicine 4 (INM-4), Forschungszentrum Jülich, 52425 Jülich, Germany
| | - Martin Wiesmann
- Department of Diagnostic and Interventional Neuroradiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany
| | - Omid Nikoubashman
- Department of Diagnostic and Interventional Neuroradiology, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany
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13
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Hoetger C, Rabinovitch AE, Henry RS, Aguayo Arelis A, Rabago Barajas BV, Perrin PB. Characterizing substance use in a sample of lesbian, gay, bisexual, and transgender adults in Mexico. J Addict Dis 2020; 39:96-104. [PMID: 33118855 DOI: 10.1080/10550887.2020.1826102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Background: Research from high-income countries on substance use among lesbian, gay, bisexual, and transgender (LGBT) adults is growing; however, limited empirical research exists on LGBT adults in Mexico. Filling this gap is critical as LGBT adults experience unique stressors that may place them at risk for substance use-related health outcomes. Objectives: This study sought to characterize substance use prevalence and magnitude among a convenience sample of Mexican LGBT adults. Methods: A cross-sectional online survey was conducted using a sample of Spanish-speaking, self-identified LGBT adults (n = 92) residing in Mexico who were recruited through online forums of LGBT-focused organizations. Descriptive and frequency analyses were conducted. Results: Participants predominantly identified as cisgender men (n = 44) and gay/lesbian (n = 68). Participants reported high rates of past 90-day legal substance use (>93% for alcohol and >57% for tobacco). The most commonly reported illicit drug used in the past 90 days was marijuana (>29%). Conclusions: While the sample reported lower prevalence and magnitude of substance use relative to other Mexican or United States LGBT samples, the findings highlight that legal and illicit substance use presents health risks for Mexican LGBT individuals. LGBT identity-affirming substance use treatment may reduce substance use-related health burden among this population.
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Affiliation(s)
- Cosima Hoetger
- Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA
| | - Annie E Rabinovitch
- Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA
| | - Richard S Henry
- Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA
| | - Adriana Aguayo Arelis
- Department of Neurosciences, CUCS, University of Guadalajara, Guadalajara, JAL, Mexico.,Department of Psychology, Enrique Diaz de Leon University, Guadalajara, JAL, Mexico
| | | | - Paul B Perrin
- Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA
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14
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Kim YS, Kim SG. Endoplasmic reticulum stress and autophagy dysregulation in alcoholic and non-alcoholic liver diseases. Clin Mol Hepatol 2020; 26:715-727. [PMID: 32951410 PMCID: PMC7641579 DOI: 10.3350/cmh.2020.0173] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/31/2020] [Indexed: 12/15/2022] Open
Abstract
Alcoholic and non-alcoholic liver diseases begin from an imbalance in lipid metabolism in hepatocytes as the earliest response. Both liver diseases share common disease features and stages (i.e., steatosis, hepatitis, cirrhosis, and hepatocellular carcinoma). However, the two diseases have differential pathogenesis and clinical symptoms. Studies have elucidated the molecular basis underlying similarities and differences in the pathogenesis of the diseases; the factors contributing to the progression of liver diseases include depletion of sulfhydryl pools, enhanced levels of reactive oxygen and nitrogen intermediates, increased sensitivity of hepatocytes to toxic cytokines, mitochondrial dysfunction, and insulin resistance. Endoplasmic reticulum (ER) stress, which is caused by the accumulation of misfolded proteins and calcium depletion, contributes to the pathogenesis, often causing catastrophic cell death. Several studies have demonstrated a mechanism by which ER stress triggers liver disease progression. Autophagy is an evolutionarily conserved process that regulates organelle turnover and cellular energy balance through decomposing damaged organelles including mitochondria, misfolded proteins, and lipid droplets. Autophagy dysregulation also exacerbates liver diseases. Thus, autophagy-related molecules can be potential therapeutic targets for liver diseases. Since ER stress and autophagy are closely linked to each other, an understanding of the molecules, gene clusters, and networks engaged in these processes would be of help to find new remedies for alcoholic and non-alcoholic liver diseases. In this review, we summarize the recent findings and perspectives in the context of the molecular pathogenesis of the liver diseases.
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Affiliation(s)
- Yun Seok Kim
- College of Pharmacy, Seoul National University, Seoul, Korea
| | - Sang Geon Kim
- College of Pharmacy, Seoul National University, Seoul, Korea.,College of Pharmacy, Dongguk University, Goyang, Korea
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15
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Ayoub SM, Minhas M, Lapointe T, Limebeer CL, Parker LA, Leri F. Effects of high fructose corn syrup on ethanol self-administration in rats. Alcohol 2020; 87:79-88. [PMID: 32497557 DOI: 10.1016/j.alcohol.2020.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 04/22/2020] [Accepted: 05/20/2020] [Indexed: 01/07/2023]
Abstract
OBJECTIVE The addition of sweeteners to alcoholic beverages is thought to facilitate heavy alcohol consumption, and this may be of particular concern when the additive is high fructose corn syrup (HFCS). METHODS Four experiments in male Sprague-Dawley rats were performed to investigate whether the addition of 25% HFCS to ethanol (5%, 10%, and 20% v/v ethanol) would alter its intraoral operant self-administration, palatability, and sensitivity to food deprivation stress. RESULTS As anticipated, HFCS drastically increased ethanol intake, and this effect appeared driven by its caloric value. Importantly, HFCS increased the persistence of operant responding following extinction in animals trained to self-administer the combination, and the addition of HFCS to ethanol changed subsequent responses to ethanol, including increased palatability and intake. CONCLUSIONS These results in rats suggest that the addition of HFCS to the list of ingredients in sweetened alcoholic beverages could play a significant role in the harmful consumption of ethanol-containing beverages.
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16
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McKetta SC, Keyes KM. Trends in U.S. women's binge drinking in middle adulthood by socioeconomic status, 2006-2018. Drug Alcohol Depend 2020; 212:108026. [PMID: 32408139 PMCID: PMC7293936 DOI: 10.1016/j.drugalcdep.2020.108026] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/07/2020] [Accepted: 04/10/2020] [Indexed: 01/09/2023]
Abstract
BACKGROUND Binge drinking causes injury and illness. Prevalence of binge drinking doubled in 2006-2018 for women in middle adulthood (ages 30 s and 40 s); these are the first cohorts for whom attaining higher education and income (both associated with increased alcohol use) are highly prevalent. It is unknown whether recent trends in binge drinking among US women aged 30-49 differ by socio-economic status (SES). METHODS We examined trends in binge drinking using nationally-representative National Health Interview Surveys (2006-2018) for women age 30-49 (N = 63,426), by education (college) and family income (<100 %, 100-199 %, 200-399 %, and >400 % of poverty line), controlling for age and race. RESULTS The odds of binge drinking increased among all women approximately 7 % annually from 2006 to 2018. The magnitude of the change increased with education; the predicted probability of binge drinking among women at lowest levels of education increased from 10 % to 13 % from 2006 to 2018 (adjusted OR [AOR] 1.02, 95 % CI 0.99, 1.04), and those with the highest education from 13%-32% (AOR 1.10, 95 % CI 1.08-1.12). Women at the lowest income increased binge drinking from 12 % to 16 % (AOR 1.03, 95 % CI 1.01-1.05) and highest income from 17 % to 36 % (AOR 1.09, 95 % CI 1.07-1.10). Interactions between education (F8554, p < 0.001) and income (F8573, p < 0.001) with time confirmed slope differences. CONCLUSIONS Nationally, women at all levels of SES increased binge drinking, but increases were most pronounced among high SES women.
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Affiliation(s)
- Sarah C McKetta
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
| | - Katherine M Keyes
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
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17
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Bataller R, Cabezas J, Aller R, Ventura-Cots M, Abad J, Albillos A, Altamirano J, Arias-Loste MT, Bañares R, Caballería J, Caballería L, Carrión JA, Diago M, Fernández Rodríguez C, Gallego R, García-Cortes M, García-Monzón C, Genescà J, Ginés P, Hernandez-Guerra M, Jorquera F, Lligoña A, Molina E, Pareja MJ, Planas R, Tomé S, Salmerón J, Romero-Gómez M. Alcohol-related liver disease. Clinical practice guidelines. Consensus document sponsored by AEEH. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 42:657-676. [PMID: 31771785 DOI: 10.1016/j.gastrohep.2019.09.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 09/02/2019] [Indexed: 02/07/2023]
Abstract
Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.
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Affiliation(s)
- Ramón Bataller
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, Estados Unidos.
| | - Joaquín Cabezas
- Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Instituto de investigación Sanitaria Valdecilla (IDIVAL), Santander, Cantabria, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España
| | - Rocío Aller
- Servicio de Gastroenterología, Hospital Clínico Universitario de Valladolid, Valladolid, España; Facultad de Medicina, Universidad de Valladolid, Valladolid, España; Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina de Valladolid, Valladolid, España
| | - Meritxell Ventura-Cots
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, Estados Unidos; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España
| | - Javier Abad
- Servicio de Gastroenterología y Hepatología, Hospital Puerta de Hierro, Madrid, España
| | - Agustín Albillos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, España
| | - José Altamirano
- Deparmento de Medicina Interna, Hospital Quironsalud, Barcelona, España
| | - María Teresa Arias-Loste
- Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Instituto de investigación Sanitaria Valdecilla (IDIVAL), Santander, Cantabria, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España
| | - Rafael Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Gastroenterología y Hepatología, Hospital Gregorio Marañón, Madrid, España
| | - Juan Caballería
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Unidad de Hepatología, Hospital Clínic, IDIBAPS, Barcelona, España
| | - Llorenç Caballería
- Unidad de Apoyo a la Investigación de la Atención Primaria en la Metropolitana Norte, Barcelona, España
| | | | - Moisés Diago
- Servicio de Aparato Digestivo, Hospital General de Valencia, Valencia, España
| | - Conrado Fernández Rodríguez
- Servicio de Gastroenterología, Hospital Universitario Fundación Alcorcón. Facultad de Medicina, Universidad Rey Juan Carlos, Alcorcón, Madrid, España
| | - Rocío Gallego
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; UGC Aparato Digestivo, Instituto de Biomedicina de Sevilla. Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, España
| | | | | | - Joan Genescà
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Medicina Interna-Hepatología, Hospital Universitario Vall d'Hebron, Institut de Recerca Vall d'Hebron (VHIR), Universitat Autònoma de Barcelona, Barcelona, España
| | - Pere Ginés
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Unidad de Apoyo a la Investigación de la Atención Primaria en la Metropolitana Norte, Barcelona, España
| | | | - Francisco Jorquera
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, IBIOMED, León, España
| | - Anna Lligoña
- Unidad de Alcohologia, Departamento de Psiquiatría, Hospital Clínic. Barcelona, España
| | - Esther Molina
- Unidad de Hepatología, Servicio de Aparato Digestivo, Hospital Clínico-Xerencia de Xestión Integrada de Santiago de Compostela, Santiago de Compostela, La Coruña, España
| | | | - Ramón Planas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; Departamento de Hepatología, Hospital Germans Trias i Pujol, Badalona, Barcelona, España
| | - Santiago Tomé
- Unidad de Trasplante Hepático, Hospital Clínico Universitario, Santiago de Compostela, La Coruña, España
| | - Javier Salmerón
- UGC de Aparato Digestivo, Hospital San Cecilio, Granada, España
| | - Manuel Romero-Gómez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, España; UGC Aparato Digestivo, Instituto de Biomedicina de Sevilla. Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, España
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18
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Roerecke M, Vafaei A, Hasan OSM, Chrystoja BR, Cruz M, Lee R, Neuman MG, Rehm J. Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2019; 114:1574-1586. [PMID: 31464740 PMCID: PMC6776700 DOI: 10.14309/ajg.0000000000000340] [Citation(s) in RCA: 225] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To systematically summarize the risk relationship between different levels of alcohol consumption and incidence of liver cirrhosis. METHODS MEDLINE and Embase were searched up to March 6, 2019, to identify case-control and cohort studies with sex-specific results and more than 2 categories of drinking in relation to the incidence of liver cirrhosis. Study characteristics were extracted and random-effects meta-analyses and meta-regressions were conducted. RESULTS A total of 7 cohort studies and 2 case-control studies met the inclusion criteria, providing data from 2,629,272 participants with 5,505 cases of liver cirrhosis. There was no increased risk for occasional drinkers. Consumption of one drink per day in comparison to long-term abstainers showed an increased risk for liver cirrhosis in women, but not in men. The risk for women was consistently higher compared to men. Drinking ≥5 drinks per day was associated with a substantially increased risk in both women (relative risk [RR] = 12.44, 95% confidence interval [CI]: 6.65-23.27 for 5-6 drinks, and RR = 24.58, 95% CI: 14.77-40.90 for ≥7 drinks) and men (RR = 3.80, 95% CI: 0.85-17.02, and RR = 6.93, 95% CI: 1.07-44.99, respectively). Heterogeneity across studies indicated an additional impact of other risk factors. DISCUSSION Alcohol is a major risk factor for liver cirrhosis with risk increasing exponentially. Women may be at higher risk compared to men even with little alcohol consumption. More high-quality research is necessary to elucidate the role of other risk factors, such as genetic vulnerability, body weight, metabolic risk factors, and drinking patterns over the life course. High alcohol consumption should be avoided, and people drinking at high levels should receive interventions to reduce their intake.
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Affiliation(s)
- Michael Roerecke
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
- Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, Ontario, Canada
| | - Afshin Vafaei
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
| | - Omer S M Hasan
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
- Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, Ontario, Canada
| | - Bethany R Chrystoja
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
- Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, Ontario, Canada
| | - Marcus Cruz
- In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada
| | - Roy Lee
- In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada
| | - Manuela G Neuman
- In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada
- Department of Pharmacology and Toxicology, Faculty of Medicine and Global Health, University of Toronto, Toronto, Ontario, Canada
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
- Dalla Lana School of Public Health (DLSPH), University of Toronto, Toronto, Ontario, Canada
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19
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Fish JN. Sexual Orientation-Related Disparities in High-Intensity Binge Drinking: Findings from a Nationally Representative Sample. LGBT Health 2019; 6:242-249. [PMID: 31184966 PMCID: PMC6645197 DOI: 10.1089/lgbt.2018.0244] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Purpose: The purpose of this study was to assess sexual orientation differences in high-intensity binge drinking using nationally representative data. Methods: Data were from the National Epidemiologic Survey on Alcohol and Related Conditions III (N = 36,309), a nationally representative sample of U.S. adults collected in 2012-2013. Sex-stratified adjusted logistic regression models were used to test sexual orientation differences in the prevalence of standard (4+ for women and 5+ for men) and high-intensity binge drinking (8+ and 12+ for women; 10+ and 15+ for men) across three dimensions of sexual orientation: sexual attraction, sexual behavior, and sexual identity. Results: Sexual minority women, whether defined on the basis of sexual attraction, behavior, or identity, were more likely than sexual majority women to engage in high-intensity binge drinking at two (adjusted odds ratios [aORs] ranging from 1.52 to 2.90) and three (aORs ranging from 1.61 to 3.27) times the standard cutoff for women (4+). Sexual minority men, depending on sexual orientation dimension, were equally or less likely than sexual majority men to engage in high-intensity binge drinking. Conclusion: This study is the first to document sexual orientation-related disparities in high-intensity binge drinking among adults in the United States using nationally representative data. The results suggest that differences in alcohol-related risk among sexual minority individuals vary depending on sex and sexual orientation dimension.
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Affiliation(s)
- Jessica N. Fish
- Department of Family Science, School of Public Health, University of Maryland, College Park, Maryland
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20
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Abdelmegeed MA, Ha SK, Choi Y, Akbar M, Song BJ. Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances. Curr Mol Pharmacol 2019; 10:207-225. [PMID: 26278393 DOI: 10.2174/1874467208666150817111114] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Revised: 08/07/2015] [Accepted: 08/07/2015] [Indexed: 12/17/2022]
Abstract
Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field.
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Affiliation(s)
- Mohamed A Abdelmegeed
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD 20892. United States
| | - Seung-Kwon Ha
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane, Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD. United States
| | - Youngshim Choi
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane, Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD. United States
| | - Mohammed Akbar
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane, Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD. United States
| | - Byoung-Joon Song
- Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane, Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD. United States
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21
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Stadlbauer V, Horvath A, Komarova I, Schmerboeck B, Feldbacher N, Wurm S, Klymiuk I, Durdevic M, Rainer F, Blesl A, Stryeck S, Madl T, Stiegler P, Leber B. A single alcohol binge impacts on neutrophil function without changes in gut barrier function and gut microbiome composition in healthy volunteers. PLoS One 2019; 14:e0211703. [PMID: 30707717 PMCID: PMC6358085 DOI: 10.1371/journal.pone.0211703] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/15/2019] [Indexed: 12/31/2022] Open
Abstract
Alcohol binge drinking is a dangerous drinking habit, associated with neurological problems and inflammation. The impact of a single alcohol binge on innate immunity, gut barrier and gut microbiome was studied. In this cohort study 15 healthy volunteers received 2 ml vodka 40% v/v ethanol/kg body weight. Neutrophil function was studied by flow cytometry; markers of gut permeability and inflammation (lactulose/mannitol/sucrose test, zonulin, calprotectin, diamino-oxidase) were studied with NMR spectroscopy and enzyme-linked immunosorbent assay in urine, stool and serum respectively. Bacterial products in serum were quantified using different reporter cell lines. Gut microbiome composition was studied by 16S rDNA sequencing and bioinformatics analysis. After a single alcohol binge, neutrophils were transiently primed and the response to E.coli stimulation with reactive oxygen species (ROS) production was transiently increased, on the other hand the percentage of neutrophils that did not perform phagocytosis increased. No changes in gut permeability, inflammatory biomarker, bacterial translocation and microbiome composition could be detected up to 4 hours after a single alcohol binge or on the next day. A single alcohol binge in young, healthy volunteers transiently impacts on neutrophil function. Although the exact biological consequence of this finding is not clear yet, we believe that this strengthens the importance to avoid any alcohol binge drinking, even in young, otherwise healthy persons.
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Affiliation(s)
- Vanessa Stadlbauer
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
- * E-mail:
| | - Angela Horvath
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
- Center for Biomarker Research in Medicine (CBmed), Graz, Austria
| | - Irina Komarova
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Bianca Schmerboeck
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
- Center for Biomarker Research in Medicine (CBmed), Graz, Austria
| | - Nicole Feldbacher
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Sonja Wurm
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Ingeborg Klymiuk
- Center for Medical Research, Core Facility Molecular Biology, Medical University of Graz, Graz, Austria
| | - Marija Durdevic
- Core Facility Computational Bioanalytics, Medical University of Graz, Graz, Austria
| | - Florian Rainer
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Andreas Blesl
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Sarah Stryeck
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Graz, Austria
- BioTechMed, Graz, Austria
| | - Tobias Madl
- Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Graz, Austria
- BioTechMed, Graz, Austria
| | - Philipp Stiegler
- Department of Transplantation Surgery, Medical University of Graz, Graz, Austria
| | - Bettina Leber
- Center for Biomarker Research in Medicine (CBmed), Graz, Austria
- Department of Transplantation Surgery, Medical University of Graz, Graz, Austria
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22
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Hagström H, Hemmingsson T, Discacciati A, Andreasson A. Risk Behaviors Associated with Alcohol Consumption Predict Future Severe Liver Disease. Dig Dis Sci 2019; 64:2014-2023. [PMID: 30761471 PMCID: PMC6584217 DOI: 10.1007/s10620-019-05509-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Excess consumption of alcohol can lead to cirrhosis, but it is unclear whether the type of alcohol and pattern of consumption affects this risk. AIMS We aimed to investigate whether type and pattern of alcohol consumption early in life could predict development of severe liver disease. METHODS We examined 43,242 adolescent men conscribed to military service in Sweden in 1970. Self-reported data on total amount and type of alcohol (wine, beer, and spirits) and risk behaviors associated with heavy drinking were registered. Population-based registers were used to ascertain incident cases of severe liver disease (defined as cirrhosis, decompensated liver disease, liver failure, hepatocellular carcinoma, or liver-related mortality). Cox regression models were used to estimate hazard ratios for development of severe liver disease. RESULTS During follow-up, 392 men developed severe liver disease. In multivariable analysis, after adjustment for BMI, smoking, use of narcotics, cardiovascular fitness, cognitive ability, and total amount of alcohol, an increased risk for severe liver disease was found in men who reported drinking alcohol to alleviate a hangover ("eye-opener"; aHR 1.47, 95% CI 1.02-2.11) and men who reported having been apprehended for being drunk (aHR 2.17, 95% CI 1.63-2.90), but not for any other risk behaviors. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits. CONCLUSIONS Certain risk behaviors can identify young men with a high risk of developing severe liver disease. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.
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Affiliation(s)
- Hannes Hagström
- Unit of Hepatology, Centre for Digestive Diseases, Karolinska University Hospital, 141 86 Stockholm, Sweden ,Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Tomas Hemmingsson
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden ,Department of Public Health Sciences, Stockholm University, Stockholm, Sweden
| | - Andrea Discacciati
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Anna Andreasson
- Stress Research Institute, Stockholm University, Stockholm, Sweden ,Division of Clinical Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden ,Department of Psychology, Macquarie University, North Ryde, NSW Australia
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23
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Zhao Q, Fritz M, Pfefferbaum A, Sullivan EV, Pohl KM, Zahr NM. Jacobian Maps Reveal Under-reported Brain Regions Sensitive to Extreme Binge Ethanol Intoxication in the Rat. Front Neuroanat 2018; 12:108. [PMID: 30618652 PMCID: PMC6297262 DOI: 10.3389/fnana.2018.00108] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 11/21/2018] [Indexed: 12/23/2022] Open
Abstract
Individuals aged 12-20 years drink 11% of all alcohol consumed in the United States with more than 90% consumed in the form of binge drinking. Early onset alcohol use is a strong predictor of future alcohol dependence. The study of the effects of excessive alcohol use on the human brain is hampered by limited information regarding the quantity and frequency of exposure to alcohol. Animal models can control for age at alcohol exposure onset and enable isolation of neural substrates of exposure to different patterns and quantities of ethanol (EtOH). As with humans, a frequently used binge exposure model is thought to produce dependence and affect predominantly corticolimbic brain regions. in vivo neuroimaging enables animals models to be examined longitudinally, allowing for each animal to serve as its own control. Accordingly, we conducted 3 magnetic resonance imaging (MRI) sessions (baseline, binge, recovery) to track structure throughout the brains of wild type Wistar rats to test the hypothesis that binge EtOH exposure affects specific brain regions in addition to corticolimbic circuitry. Voxel-based comparisons of 13 EtOH- vs. 12 water- exposed animals identified significant thalamic shrinkage and lateral ventricular enlargement as occurring with EtOH exposure, but recovering with a week of abstinence. By contrast, pretectal nuclei and superior and inferior colliculi shrank in response to binge EtOH treatment but did not recover with abstinence. These results identify brainstem structures that have been relatively underreported but are relevant for localizing neurocircuitry relevant to the dynamic course of alcoholism.
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Affiliation(s)
- Qingyu Zhao
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Michael Fritz
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Adolf Pfefferbaum
- Neuroscience Program, SRI International, Menlo Park, CA, United States
| | - Edith V. Sullivan
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
| | - Kilian M. Pohl
- Neuroscience Program, SRI International, Menlo Park, CA, United States
| | - Natalie M. Zahr
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
- Neuroscience Program, SRI International, Menlo Park, CA, United States
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24
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Testino G, Bottaro LC, Balbinot P, Leone S, Pellicano R. Alcohol use disorders, cardiomyopathy and heart transplantation: a new management. Minerva Cardioangiol 2018; 66:744-746. [PMID: 29792019 DOI: 10.23736/s0026-4725.18.04725-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Gianni Testino
- Alcohological Regional Center - Ligurian Region, ASL3 at San Martino Policlinic Hospital, Genoa, Italy -
| | | | - Patrizia Balbinot
- Alcohological Regional Center - Ligurian Region, ASL3 at San Martino Policlinic Hospital, Genoa, Italy
| | - Silvia Leone
- Alcohological Regional Center - Ligurian Region, ASL3 at San Martino Policlinic Hospital, Genoa, Italy
| | - Rinaldo Pellicano
- Unit of Gastroenterology and Hepatology, Molinette Hospital, Turin, Italy
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25
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Lee YJ, Hsu JD, Lin WL, Kao SH, Wang CJ. Upregulation of caveolin-1 by mulberry leaf extract and its major components, chlorogenic acid derivatives, attenuates alcoholic steatohepatitis via inhibition of oxidative stress. Food Funct 2018; 8:397-405. [PMID: 28074952 DOI: 10.1039/c6fo01539e] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Excessive alcohol uptake exerts hepatocellular toxicity, ultimately leading to multiple liver diseases such as steatohepatitis and liver cirrhosis. Here, we aimed to explore the effects of mulberry leaf extract (MLE) and its major components chlorogenic acid (CGA) and neochlorogenic acid (nCGA) on alcoholic steatohepatitis. We determined the composition of MLE using liquid chromatography-mass spectrometric (LC-MS) analysis, which showed that MLE consisted of mainly chlorogenic acid derivatives and other polyphenols. Next, we utilized a high alcohol-fed mouse model and demonstrated that MLE alleviated alcohol-induced hepatocellular disorders, resulting in lowered hepatic injury markers and lipid accumulation. In addition, MLE reduced lipid peroxidation and meanwhile elevated hepatic superoxide dismutase (SOD). Immunohistochemical (IHC) staining revealed that MLE elevated the expression of caveolin-1 but reduced the expressions of epidermal growth factor receptor (EGFR), signal transducer and activator of transcription (STAT), inducible nitric oxide synthase (iNOS) and receptor interacting protein (RIP) 1/3. Major components of MLE, CGA and nCGA, not only exerted a similar biological activity as MLE but also inhibited alcohol-induced pro-apoptotic signals. Involvement of caveolin-1 in MLE, CGA and nCGA was demonstrated by using specific small inhibitory RNA. In conclusion, MLE and its chlorogenic derivatives CGA and nCGA upregulate caveolin-1 expression and diminish EGFR/STAT3/iNOS signalling, which may contribute to lowered hepatic lipid accumulation and peroxidation and inhibited pro-apoptotic cascades.
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Affiliation(s)
- Yi-Ju Lee
- Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan and Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
| | - Jeng-Dong Hsu
- Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan and Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Wea-Lung Lin
- Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan and Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Shao-Hsuan Kao
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
| | - Chau-Jong Wang
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan and Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
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26
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Mellinger JL, Shedden K, Winder GS, Tapper E, Adams M, Fontana RJ, Volk ML, Blow FC, Lok ASF. The high burden of alcoholic cirrhosis in privately insured persons in the United States. Hepatology 2018; 68:872-882. [PMID: 29579356 DOI: 10.1002/hep.29887] [Citation(s) in RCA: 163] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Revised: 02/13/2018] [Accepted: 03/01/2018] [Indexed: 12/13/2022]
Abstract
UNLABELLED Alcoholic cirrhosis (AC) is a major cause of liver-related morbidity and mortality in the United States. Rising rates of alcohol use disorders in the United States will likely result in more alcoholic liver disease. Our aim was to determine the prevalence, health care use, and costs of AC among privately insured persons in the United States. We collected data from persons aged 18-64 with AC (identified by codes from the International Classification of Diseases, Ninth and Tenth Revisions) enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009-2015). We determined yearly prevalence, weighted to the national employer-sponsored, privately insured population. Using competing risk analysis, we estimated event rates for portal hypertensive complications and estimated the association between AC and costs as well as admissions and readmissions. In 2015, 294,215 people had cirrhosis and 105,871 (36%) had AC. Mean age at AC diagnosis was 53.5 years, and 32% were women. Over the 7 years queried, estimated national cirrhosis prevalence rose from 0.19% to 0.27% (P < 0.001) and for AC from 0.07% to 0.10% (P < 0.001). Compared to non-AC, AC enrollees were significantly more likely to have portal hypertensive complications at diagnosis and higher yearly cirrhosis and alcohol-related admissions (25 excess cirrhosis admissions and 6.3 excess alcohol-related admissions per 100 enrollees) as well as all-cause readmissions. Per-person costs in the first year after diagnosis nearly doubled for AC versus non-AC persons (US$ 44,835 versus 23,319). CONCLUSION In a nationally representative cohort of privately insured persons, AC enrollees were disproportionately sicker at presentation, were admitted and readmitted more often, and incurred nearly double the per-person health care costs compared to those with non-AC. (Hepatology 2018).
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Affiliation(s)
- Jessica L Mellinger
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Kerby Shedden
- Department of Statistics, University of Michigan, Ann Arbor, MI
| | - Gerald Scott Winder
- Department of Psychiatry, VA Center for Clinical Management Research, Ann Arbor, MI
| | - Elliot Tapper
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Megan Adams
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI.,VA Center for Clinical Management Research, Ann Arbor, MI
| | - Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Michael L Volk
- Transplantation Institute, Loma Linda University Health, Loma Linda, CA
| | - Frederic C Blow
- Department of Psychiatry, VA Center for Clinical Management Research, Ann Arbor, MI.,VA Center for Clinical Management Research, Ann Arbor, MI
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
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27
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Fuller A, Fleming KM, Szatkowski L, Bains M. Nature of events and alcohol-related content in marketing materials at a university freshers' fair: a summative content analysis. J Public Health (Oxf) 2018; 40:e320-e327. [PMID: 29253185 DOI: 10.1093/pubmed/fdx181] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Indexed: 11/12/2022] Open
Abstract
Introduction The transition to university is a potentially influential time upon students' drinking behaviour. This study explored the nature of activities and alcohol-related content in marketing materials from student-led societies and local businesses provided to students, at a university freshers' fair in the UK. Methods All marketing materials handed out at the fair were collected across the 5-day event in September 2015. Written and visual content was analysed using a summative qualitative content analysis. Results Most student-led societies promoted social events they were hosting (n = 530), most of which took place in a drinking venue or referred to drinking (n = 335). Only four explicitly alcohol-free events were promoted. Student-led societies also promoted activities relating to their interest, e.g. sports training (n = 519), a small proportion of which had references to drinking and drinking venues (n = 54). Three societies provided promotional handouts from local bars or nightclubs. Local bars, pubs and nightclubs promoted events they hosted (n = 81) as well as alcoholic drink promotions (n = 79) and alcohol branded advertising (n = 22), albeit infrequently for the latter. Conclusions In the first week of university, students are exposed to alcohol-related events, promotions and advertising, which may act as an incentive to participate in drinking.
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Affiliation(s)
- A Fuller
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - K M Fleming
- Department of Public Health and Policy, Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK
| | - L Szatkowski
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
| | - M Bains
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
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28
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Sun X, Wang P, Yao LP, Wang W, Gao YM, Zhang J, Fu YJ. Paeonol alleviated acute alcohol-induced liver injury via SIRT1/Nrf2/NF-κB signaling pathway. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2018; 60:110-117. [PMID: 29704732 DOI: 10.1016/j.etap.2018.04.016] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 04/16/2018] [Accepted: 04/20/2018] [Indexed: 05/22/2023]
Abstract
In this study, the beneficial effect of paeonol on acute alcohol-induced liver injury and the basic mechanisms were investigated. in vitro, HepG2 cells were treated with paeonol for 24 h before it were exposed to alcohol for 24 h. in vivo, male C57BL/6 mice were used to establish alcohol-induced liver injury models by oral gavage of alcohol (5 g/kg BW). Paeonol pretreatment showed statistically significant reduction in alcohol-induced ROS, MDA, IL-1β, IL-6, TNF-α, and nitric oxide, while GSH content was retained (P < 0.05). Furthermore, paeonol treatment resulted in the increase of Nrf2 nuclear translocation, the increase of NQO-1 and HO-1 expression, and the suppression of NF-κB p65 nuclear translocation. However, pretreatment with NAM (inhibitor of SIRT1) not only inhibited the effect of paeonol on reducing nuclear translocation of NF-κBp65, but also inhibited the effect of paeonol on promoting the expression of nuclear Nrf2, NQO1 and HO-1. Besides, paeonol pretreatment at test doses significantly ameliorated alcohol-induced edema, hepatocyte necrosis and hepatic cord irregular. These results demonstrated that paeonol has the high potential for relieving acute alcohol-induced liver injury.
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Affiliation(s)
- Xing Sun
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China
| | - Peng Wang
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China
| | - Li-Ping Yao
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China
| | - Wei Wang
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China
| | - Yi-Meng Gao
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China
| | - Jing Zhang
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China
| | - Yu-Jie Fu
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Harbin 150040, PR China; Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China; The college of Forestry, Beijing Forestry University, Beijing 100083, PR China.
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29
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Bertola A. WITHDRAWN: Rodent models of fatty liver diseases. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2018.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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30
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Irwin C, Mienie LJ, Wevers RA, Mason S, Westerhuis JA, van Reenen M, Reinecke CJ. GC-MS-based urinary organic acid profiling reveals multiple dysregulated metabolic pathways following experimental acute alcohol consumption. Sci Rep 2018; 8:5775. [PMID: 29636520 PMCID: PMC5893584 DOI: 10.1038/s41598-018-24128-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Accepted: 03/22/2018] [Indexed: 12/14/2022] Open
Abstract
Metabolomics studies of diseases associated with chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways. Moreover, the holistic approach of such studies gives insights into the pathophysiological risk factors associated with chronic alcohol-induced disability, morbidity and mortality. Here, we report on a GC-MS-based organic acid profiling study on acute alcohol consumption. Our investigation - involving 12 healthy, moderate-drinking young men - simulated a single binge drinking event, and indicated its metabolic consequences. We generated time-dependent data that predicted the metabolic pathophysiology of the alcohol intervention. Multivariate statistical modelling was applied to the longitudinal data of 120 biologically relevant organic acids, of which 13 provided statistical evidence of the alcohol effect. The known alcohol-induced increased NADH:NAD+ ratio in the cytosol of hepatocytes contributed to the global dysregulation of several metabolic reactions of glycolysis, ketogenesis, the Krebs cycle and gluconeogenesis. The significant presence of 2-hydroxyisobutyric acid supports the emerging paradigm that this compound is an important endogenous metabolite. Its metabolic origin remains elusive, but recent evidence indicated 2-hydroxyisobutyrylation as a novel regulatory modifier of histones. Metabolomics has thus opened an avenue for further research on the reprogramming of metabolic pathways and epigenetic networks in relation to the severe effects of alcohol consumption.
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Affiliation(s)
- Cindy Irwin
- Centre for Human Metabolomics, Faculty of Natural Sciences and Agriculture, North-West University (Potchefstroom Campus), Private Bag, X6001, Potchefstroom, South Africa
| | - Lodewyk J Mienie
- Centre for Human Metabolomics, Faculty of Natural Sciences and Agriculture, North-West University (Potchefstroom Campus), Private Bag, X6001, Potchefstroom, South Africa
| | - Ron A Wevers
- Radboud University Nijmegen Medical Centre, Translational Metabolic Laboratory, Department of Laboratory Medicine, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Shayne Mason
- Centre for Human Metabolomics, Faculty of Natural Sciences and Agriculture, North-West University (Potchefstroom Campus), Private Bag, X6001, Potchefstroom, South Africa
| | - Johan A Westerhuis
- Centre for Human Metabolomics, Faculty of Natural Sciences and Agriculture, North-West University (Potchefstroom Campus), Private Bag, X6001, Potchefstroom, South Africa
- Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Mari van Reenen
- Department of Statistics, Faculty of Natural Sciences and Agriculture, North-West University (Potchefstroom Campus), Private Bag, X6001, Potchefstroom, South Africa
| | - Carolus J Reinecke
- Centre for Human Metabolomics, Faculty of Natural Sciences and Agriculture, North-West University (Potchefstroom Campus), Private Bag, X6001, Potchefstroom, South Africa.
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31
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Fish JN, Hughes TL, Russell ST. Sexual identity differences in high-intensity binge drinking: findings from a US national sample. Addiction 2018; 113:749-758. [PMID: 28940778 PMCID: PMC5847413 DOI: 10.1111/add.14041] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/07/2017] [Accepted: 09/15/2017] [Indexed: 01/06/2023]
Abstract
AIM To estimate sexual identity differences in high-intensity binge drinking. DESIGN AND SETTING Cross-sectional US adult health survey from 2014 and 2015. PARTICIPANTS US adults aged 18 and older (n = 215 684; n = 203 562 heterosexual, n = 2784 lesbian/gay, n = 2892 bisexual, n = 686 'other' and n = 1947 don't know/unsure). MEASUREMENTS Self-reported past 30-day standard binge and high-intensity binge drinking. Standard binge drinking cut-off values were 4+/5+ drinks for women and men, respectively. High-intensity binge drinking was measured as two and three times the standard level (8+ and 12+ drinks for women and 10+ and 15+ drinks for men). FINDINGS Lesbian and bisexual women were more likely than heterosexual women to report consuming 4+ drinks (adjusted odds ratio [aOR] =1.57, confidence interval [CI] = 1.18, 2.09 and aOR = 1.83, CI = 1.45, 2.30 for lesbian and bisexual women, respectively); 8+ drinks (aOR = 3.86, CI = 2.39, 6.24, aOR = 2.07, CI = 1.39, 3.07); and 12+ drinks (aOR = 3.81, CI = 1.77, 8.19, aOR = 2.54, CI = 1.25, 5.14) on a single occasion in the past 30 days. Generally, gay and bisexual men were no more likely than heterosexual men to report standard or high-intensity binge drinking. However, bisexual men were more likely than heterosexual men to consume 15+ drinks (aOR = 1.76, 95% CI = 1.01, 3.06). Rates of standard and high-intensity binge drinking were similar between heterosexual and unsure men and women. Men and women who indicated 'other' sexual identities were generally less likely than heterosexuals to report standard and high-intensity binge drinking, with the exception of 4+ drinks for women and 10+ drinks for men. CONCLUSIONS In the United States, sexual minority women are more likely, and sexual minority men are equally likely, to drink at standard and high-intensity binge drinking levels as their heterosexual counterparts.
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Affiliation(s)
- Jessica N. Fish
- Population Research Center, Human Development and Family Sciences, University of Texas at Austin, 305 E. 23 St., Stop G1800, Austin, TX 78712
| | - Tonda L. Hughes
- School of Nursing, Columbia University, 617 W 168 Street, New York, NY, 10032
| | - Stephen T. Russell
- Human Development and Family Sciences, Population Research Center, University of Texas at Austin, 108 E. Dean Keeton St., Stop A2702, Austin, TX, 78712
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Louvet A, Krag A. Managing excessive alcohol consumption at a population level: The earlier the better. J Hepatol 2018; 68:389-390. [PMID: 29395456 DOI: 10.1016/j.jhep.2017.12.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 12/18/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Alexandre Louvet
- Service des maladies de l'appareil digestif, Hôpital Huriez, Rue Polonowski, 59037 Lille cedex, France.
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
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Morris LS, Dowell NG, Cercignani M, Harrison NA, Voon V. Binge drinking differentially affects cortical and subcortical microstructure. Addict Biol 2018; 23:403-411. [PMID: 28105707 PMCID: PMC5811821 DOI: 10.1111/adb.12493] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 12/21/2016] [Accepted: 01/03/2017] [Indexed: 01/18/2023]
Abstract
Young adult binge drinkers represent a model for endophenotypic risk factors for alcohol misuse and early exposure to repeated binge cycles. Chronic or harmful alcohol use leads to neurochemical, structural and morphological neuroplastic changes, particularly in regions associated with reward processing and motivation. We investigated neural microstructure in 28 binge drinkers compared with 38 matched healthy controls. We used a recently developed diffusion magnetic resonance imaging acquisition and analysis, which uses three‐compartment modelling (of intracellular, extracellular and cerebrospinal fluid) to determine brain tissue microstructure features including neurite density and orientation dispersion index (ODI). Binge drinkers had reduced ODI, a proxy of neurite complexity, in frontal cortical grey matter and increased ODI in parietal grey matter. Neurite density was higher in cortical white matter in adjacent regions of lower ODI in binge drinkers. Furthermore, binge drinkers had higher ventral striatal grey matter ODI that was positively correlated with binge score. Healthy volunteers showed no such relationships. We demonstrate disturbed dendritic complexity of higher‐order prefrontal and parietal regions, along with higher dendritic complexity of a subcortical region known to mediate reward‐related motivation. The findings illustrate novel microstructural abnormalities that may reflect an infnce of alcohol bingeing on critical neurodevelopmental processes in an at‐risk young adult group.
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Affiliation(s)
- Laurel S. Morris
- Behavioural and Clinical Neuroscience Institute; University of Cambridge; Cambridge UK
- Department of Psychology; University of Cambridge; Cambridge UK
| | - Nicholas G. Dowell
- Department of Psychiatry; Brighton and Sussex Medical School; Brighton UK
| | - Mara Cercignani
- Department of Psychiatry; Brighton and Sussex Medical School; Brighton UK
| | - Neil A. Harrison
- Department of Psychiatry; Brighton and Sussex Medical School; Brighton UK
| | - Valerie Voon
- Behavioural and Clinical Neuroscience Institute; University of Cambridge; Cambridge UK
- Department of Psychiatry; University of Cambridge, Addenbrooke's Hospital; Cambridge UK
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Marot A, Henrion J, Knebel JF, Moreno C, Deltenre P. Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study. PLoS One 2017; 12:e0186715. [PMID: 29077714 PMCID: PMC5659599 DOI: 10.1371/journal.pone.0186715] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 10/08/2017] [Indexed: 02/07/2023] Open
Abstract
Background Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear. Aim To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death. Methods Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78). Results At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis. Conclusion Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis.
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Affiliation(s)
- Astrid Marot
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Lausanne, Switzerland
| | - Jean Henrion
- Division of Gastroenterology and Hepatology, Centres hospitaliers de Jolimont, Haine-Saint-Paul, Belgium
| | - Jean-François Knebel
- Laboratory for Investigative Neurophysiology (The LINE), Department of Radiology and Department of Clinical Neurosciences, University Hospital Center and University of Lausanne, Lausanne, Switzerland
- EEG Brain Mapping Core, Centre for Biomedical Imaging (CIBM), Lausanne, Switzerland
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Pierre Deltenre
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Lausanne, Switzerland
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
- * E-mail:
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Is there a relationship between adverse childhood experiences and problem drinking behaviors? Findings from a population-based sample. Public Health 2017. [DOI: 10.1016/j.puhe.2017.05.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Atkinson SR, Vergis N, Louvet A, Thursz MR. Universal screening of acute medical admissions for excess alcohol consumption: What's the misuse? J Hepatol 2017; 67:448-450. [PMID: 28756906 DOI: 10.1016/j.jhep.2017.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 06/02/2017] [Accepted: 06/07/2017] [Indexed: 12/04/2022]
Affiliation(s)
- Stephen R Atkinson
- Department of Hepatology, Division of Surgery and Cancer, Imperial College London, UK
| | - Nikhil Vergis
- Department of Hepatology, Division of Surgery and Cancer, Imperial College London, UK
| | - Alexandre Louvet
- Service des maladies de l'appareil digestif, Hôpital Huriez, Lille, France.
| | - Mark R Thursz
- Department of Hepatology, Division of Surgery and Cancer, Imperial College London, UK.
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Åberg F, Helenius-Hietala J, Puukka P, Jula A. Binge drinking and the risk of liver events: A population-based cohort study. Liver Int 2017; 37:1373-1381. [PMID: 28276137 DOI: 10.1111/liv.13408] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 02/26/2017] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Binge drinking or heavy episodic drinking is increasingly prevalent, but the health effects are incompletely understood. We investigated whether binge drinking increases the risk for liver disease above and beyond the risk due to average alcohol consumption. METHODS 6366 subjects without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analysed for liver-related admissions, mortality and liver cancer. Binge drinking (≥5 drinks per occasion, standard drink 12 g ethanol) was categorised as weekly, monthly, or as less often or none. Multiple confounders were considered. RESULTS Eighty-four subjects developed decompensated liver disease. Binge drinking frequency showed a direct association with liver-disease risk after adjustment for average daily alcohol intake and age. After adjustment, the hazard ratios (HRs) for weekly and monthly binge drinking were 3.45 (P=.001) and 2.26 (P=.007) and were higher after excluding regular heavy drinkers. The HR for weekly binging was 6.82 (P=.02) in women; 2.34 (P=.03) in men; and 4.29 (P=.001) in subjects with the metabolic syndrome. Weekly binge drinking and the metabolic syndrome produced supra-additive increases in the risk of decompensated liver disease. Weekly, and to a lesser extent monthly, binging retained significance in sequential multivariate models that additionally adjusted for beverage preference and lifestyle, metabolic, and socioeconomic factors. CONCLUSIONS Binge drinking is associated with an increased risk for liver disease independently of average alcohol intake and confounders. The rising prevalence of binge drinking and the metabolic syndrome is particularly concerning.
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Affiliation(s)
- Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki University, Helsinki, Finland
| | - Jaana Helenius-Hietala
- Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki University, Helsinki, Finland
| | - Pauli Puukka
- Department of Health, National Institute for Health and Welfare, Turku, Finland
| | - Antti Jula
- Department of Health, National Institute for Health and Welfare, Turku, Finland
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Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues. Toxicology 2017; 390:53-60. [DOI: 10.1016/j.tox.2017.09.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 08/23/2017] [Accepted: 09/01/2017] [Indexed: 02/07/2023]
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Seltzman HH, Maitra R, Bortoff K, Henson J, Reggio PH, Wesley D, Tam J. Metabolic Profiling of CB1 Neutral Antagonists. Methods Enzymol 2017; 593:199-215. [PMID: 28750803 DOI: 10.1016/bs.mie.2017.06.025] [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] [Indexed: 12/17/2022]
Abstract
PIMSR is among the first neutral antagonists for the CB1R and was demonstrated pharmacologically to bind to the CB1R, yet not alter calcium flux. It was further shown computationally to be able to stabilize both the active and inactive states of CB1R revealing the molecular interactions that mechanistically afford the property of neutral antagonism. PIMSR shows dramatic positive effects in reducing weight, food intake, and adiposity as well as in improving glycemic control and lipid homeostasis in high-fat diet-induced obese mice, but also shows increased ALT and liver weight as markers of liver injury with chronic administration. Further, in a separate study, 3-day administration of PIMSR in C57BL/6J mice, hepatic steatosis from an acute administration of high of ethanol was significantly reduced. Also, it partially prevented alcohol-induced increases in ALT, AST, and LDH. The differences in ALT levels in obese and nonobese mice under different test paradigms are unlikely to be due to neutral antagonism itself since other neutral antagonists (AM6545) do not exhibit liver injury. The brain levels of low micromolar would support significant brain CB1 receptor occupancy (re: Ki=17nM), thus potentially including both CNS and peripheral influences on the observed weight loss. Overall, these studies suggest that marked improvements in aspects of metabolic disease and alcoholic steatosis can be realized with CB1R neutral antagonists and hence warrants the exploration of further members of this class of cannabinoid ligands.
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Affiliation(s)
- Herbert H Seltzman
- Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, NC, United States.
| | - Rangan Maitra
- Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, NC, United States
| | | | | | - Patricia H Reggio
- University of North Carolina at Greensboro, Greensboro, NC, United States
| | - Daniel Wesley
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, United States
| | - Joseph Tam
- Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
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Doycheva I, Watt KD, Rifai G, Abou Mrad R, Lopez R, Zein NN, Carey WD, Alkhouri N. Increasing Burden of Chronic Liver Disease Among Adolescents and Young Adults in the USA: A Silent Epidemic. Dig Dis Sci 2017; 62:1373-1380. [PMID: 28194666 DOI: 10.1007/s10620-017-4492-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 02/06/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Chronic liver disease (CLD) starts or becomes established in the adolescent and young adult (AYA) age group. This study aimed to estimate trends in CLD prevalence among US AYAs and to assess factors associated with CLD. METHODS Cross-sectional data from 14,547 AYAs (population-weighted N = 68,274,386) aged 15-39 years enrolled in the National Health and Nutrition Examination Survey from 1988 to 2012 were used. Nonalcoholic fatty liver disease (NAFLD) was defined as elevated alanine aminotransferase (>19 U/L for females and >30 U/L for males) in subjects with BMI ≥ 25 kg/m2; alcoholic liver disease (ALD) as excessive alcohol use (≥3 drinks/day for men and ≥2 drinks/day for women) and elevated aminotransferases after excluding alternative etiologies. Participants were considered hepatitis C virus (HCV) positive if antibody to HCV and HCV-RNA was positive. RESULTS There was a sharp increase in the prevalence of CLD from 12.9% in 1988-1994 to 28.5% in 1999-2004 that remained stable after that (27.7%). NAFLD was the most common etiology accounting for 22% of all CLD in the later period. The prevalence of ALD has been steadily increasing throughout the years, while HCV has been decreasing. On multivariate analysis, being overweight/obese, Mexican-American ethnicity, later study period, older age, and male gender, were associated with higher odds of having CLD. CONCLUSION More than one quarter of US AYAs might be affected by CLD. CLD prevalence in this age group has more than doubled over the past three decades mainly due to rise in NAFLD prevalence.
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Affiliation(s)
- Iliana Doycheva
- Division of Gastroenterology and Hepatology, Medical University, Sofia, Bulgaria
| | - Kymberly D Watt
- Gastroenterology and Hepatology Department, Mayo Clinic, Rochester, MN, USA
| | - Ghassoub Rifai
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Rachel Abou Mrad
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Rocio Lopez
- Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Nizar N Zein
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - William D Carey
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Naim Alkhouri
- Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA. .,Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic Children's Hospital, 9500 Euclid Avenue, A-111, Cleveland, OH, 44195, USA.
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Zeng T, Zhang CL, Xiao M, Yang R, Xie KQ. Critical Roles of Kupffer Cells in the Pathogenesis of Alcoholic Liver Disease: From Basic Science to Clinical Trials. Front Immunol 2016; 7:538. [PMID: 27965666 PMCID: PMC5126119 DOI: 10.3389/fimmu.2016.00538] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 11/15/2016] [Indexed: 12/12/2022] Open
Abstract
Alcoholic liver disease (ALD) encompasses a spectrum of liver injury ranging from steatosis to steatohepatitis, fibrosis, and finally cirrhosis. Accumulating evidences have demonstrated that Kupffer cells (KCs) play critical roles in the pathogenesis of both chronic and acute ALD. It has become clear that alcohol exposure can result in increased hepatic translocation of gut-sourced endotoxin/lipopolysaccharide, which is a strong M1 polarization inducer of KCs. The activated KCs then produce a large amount of reactive oxygen species (ROS), pro-inflammatory cytokines, and chemokines, which finally lead to liver injury. The critical roles of KCs and related inflammatory cascade in the pathogenesis of ALD make it a promising target in pharmaceutical drug developments for ALD treatment. Several drugs (such as rifaximin, pentoxifylline, and infliximab) have been evaluated or are under evaluation for ALD treatment in randomized clinical trials. Furthermore, screening pharmacological regulators for KCs toward M2 polarization may provide additional therapeutic agents. The combination of these potentially therapeutic drugs with hepatoprotective agents (such as zinc, melatonin, and silymarin) may bring encouraging results.
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Affiliation(s)
- Tao Zeng
- Institute of Toxicology, School of Public Health, Shandong University , Jinan , China
| | - Cui-Li Zhang
- Institute of Toxicology, School of Public Health, Shandong University , Jinan , China
| | - Mo Xiao
- Institute of Toxicology, School of Public Health, Shandong University , Jinan , China
| | - Rui Yang
- Institute of Toxicology, School of Public Health, Shandong University , Jinan , China
| | - Ke-Qin Xie
- Institute of Toxicology, School of Public Health, Shandong University , Jinan , China
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Stein E, Cruz-Lemini M, Altamirano J, Ndugga N, Couper D, Abraldes JG, Bataller R. Heavy daily alcohol intake at the population level predicts the weight of alcohol in cirrhosis burden worldwide. J Hepatol 2016; 65:998-1005. [PMID: 27392424 DOI: 10.1016/j.jhep.2016.06.018] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 05/27/2016] [Accepted: 06/14/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Studies assessing alcohol as a population level risk factor for cirrhosis typically focus on per capita consumption. However, clinical studies indicate that daily intake is a strong predictor of alcoholic cirrhosis. We aimed to identify the determinants of alcohol's contribution to the global cirrhosis burden and to evaluate the influence of daily drinking on a population level. METHODS We performed a comprehensive analysis of the WHO 2014 Global Status Report on Alcohol and Health. We categorized countries by heavy or moderate drinking based on daily consumption, using U.S. Department of Agriculture definitions of heavy drinking. Additional data on cirrhosis cofactors were also obtained. Uni- and multivariate models were fitted to identify independent predictors of the alcohol-attributable fraction of cirrhosis. RESULTS The WHO 2014 Report found that half of cirrhosis mortality worldwide is attributable to alcohol, approximating 60% in North America and Europe. In an integrative multivariate model, the designation of countries by moderate or heavy daily drinking had the strongest influence on the weight of alcohol in the cirrhosis burden. The relative contribution from alcohol increased by 11% with a transition from the moderate to heavy classification (p<0.001). Importantly, drinking patterns such as heavy episodic drinking and the type of alcohol did not independently predict the alcohol-attributable fraction of cirrhosis. CONCLUSIONS Heavy daily drinking on a population level significantly influences the weight of alcohol in the cirrhosis burden. Reducing heavy drinking should be considered as an important target for public health monitoring and policies. LAY SUMMARY We carried out an analysis of the WHO 2014 Global Status Report on Alcohol and Health, and categorized countries by their level of drinking (heavy or moderate). We found that half of the global cirrhosis cases, and 60% in both North America and Europe are associated with alcohol intake. We concluded that on a population level heavy daily drinking significantly influences the impact of alcohol on the cirrhosis burden.
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Affiliation(s)
- Eva Stein
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | | | - Jose Altamirano
- Vall d'Hebrón Institut de Recerca, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Nambi Ndugga
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - David Couper
- Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA
| | - Juan G Abraldes
- Cirrhosis Care Clinic, Liver Unit, Division of Gastroenterology, Department of Medicine, CEGIIR, University of Alberta, Edmonton, Canada
| | - Ramon Bataller
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Division of Biochemistry, Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
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Vandenbulcke H, Moreno C, Colle I, Knebel JF, Francque S, Sersté T, George C, de Galocsy C, Laleman W, Delwaide J, Orlent H, Lasser L, Trépo E, Van Vlierberghe H, Michielsen P, van Gossum M, de Vos M, Marot A, Doerig C, Henrion J, Deltenre P. Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study. J Hepatol 2016; 65:543-51. [PMID: 27180899 DOI: 10.1016/j.jhep.2016.04.031] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Revised: 04/05/2016] [Accepted: 04/27/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.
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Affiliation(s)
- Hélène Vandenbulcke
- Departement of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Isabelle Colle
- Departement of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Jean-François Knebel
- Laboratory for Investigative Neurophysiology (The LINE), Department of Radiology and Department of Clinical Neurosciences, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland; EEG Brain Mapping Core, Centre for Biomedical Imaging (CIBM), 1011 Lausanne, Switzerland
| | - Sven Francque
- Departement of Gastroenterology and Hepatology, UZ Antwerpen, Edegem, Belgium
| | - Thomas Sersté
- Departement of Gastroenterology and Hepatology, CHU Saint-Pierre, Brussels, Belgium
| | - Christophe George
- Departement of Gastroenterology and Hepatology, AZ Groeninge, Kortrijk, Belgium
| | - Chantal de Galocsy
- Departement of Gastroenterology and Hepatology, Hôpitaux Iris Sud Bracops, Brussels, Belgium
| | - Wim Laleman
- Departement of Gastroenterology and Hepatology, KUL, Leuven, Belgium
| | - Jean Delwaide
- Departement of Gastroenterology and Hepatology, CHU Liège, Liège, Belgium
| | - Hans Orlent
- Departement of Gastroenterology and Hepatology, AZ St Jan, Brugge, Belgium
| | - Luc Lasser
- Departement of Gastroenterology and Hepatology, CHU Brugmann, Brussels, Belgium
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Hans Van Vlierberghe
- Departement of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Peter Michielsen
- Departement of Gastroenterology and Hepatology, UZ Antwerpen, Edegem, Belgium
| | - Marc van Gossum
- Departement of Gastroenterology and Hepatology, CHU Saint-Pierre, Brussels, Belgium
| | - Marie de Vos
- Departement of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Astrid Marot
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Christopher Doerig
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Jean Henrion
- Departement of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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Addolorato G, Mirijello A, Barrio P, Gual A. Treatment of alcohol use disorders in patients with alcoholic liver disease. J Hepatol 2016; 65:618-30. [PMID: 27155530 DOI: 10.1016/j.jhep.2016.04.029] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 03/24/2016] [Accepted: 04/25/2016] [Indexed: 12/18/2022]
Abstract
Alcohol use disorders (AUDs) is one of the leading causes of disease and disability in almost all European countries. Among the alcohol-related diseases, alcoholic liver disease (ALD) is the most common. At present, alcohol is the most frequent cause of liver cirrhosis in the Western world. The cornerstone of treatment for ALD is achieving total alcohol abstinence and preventing relapse; medical and surgical treatments for ALD are limited when drinking continues. This narrative review summarizes current treatments for AUDs with a particular emphasis to the treatment of AUDs in patients with ALD. Medical management, psychosocial and pharmacological interventions are analyzed, underlying limits and options in AUD patients. Finally, this review discusses the most appropriate setting for the management of AUD patients with advanced liver disease as well as the indications for liver transplantation in AUD patients.
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Affiliation(s)
- Giovanni Addolorato
- Alcohol Use Disorders Unit, Department of Internal Medicine, Gastroenterology and Hepatology, Catholic University of Rome, Italy.
| | - Antonio Mirijello
- Alcohol Use Disorders Unit, Department of Internal Medicine, Gastroenterology and Hepatology, Catholic University of Rome, Italy; Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, FG, Italy
| | - Pablo Barrio
- Department of Psychiatry, Neurosciences Institute, Hospital Clínic, IDIBAPS, Barcelona, Spain
| | - Antoni Gual
- Department of Psychiatry, Neurosciences Institute, Hospital Clínic, IDIBAPS, Barcelona, Spain.
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Ethnicity matters: A Systematic Review and Meta-Analysis of the Non-Linear Relationship Between Alcohol Consumption and Prevalence and Incidence of Hepatic Steatosis. EBioMedicine 2016; 8:317-330. [PMID: 27428441 PMCID: PMC4919723 DOI: 10.1016/j.ebiom.2016.04.023] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 04/14/2016] [Accepted: 04/18/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Fatty liver (hepatic steatosis) is one of the most common diseases globally, with increasing prevalence. The role of alcohol consumption in the development of hepatic steatosis has not been systematically examined. METHODS We searched Medline, Embase, and ProQuest Dissertations & Theses Global for original data on the relationship between alcohol consumption and hepatic steatosis measured by non-invasive imagery, excluding studies conducted in participants <18years, or subgroups related to viral and drug-induced liver disease. We identified 18 articles reporting adjusted data (Japan=11, other high-income countries=7). Random-effect categorical meta-analyses (<20g/day pure alcohol consumption vs non-drinkers) and dose-response meta-analyses for the whole range of alcohol consumption were conducted. RESULTS In total, 99,370 participants and 25,662 cases of hepatic steatosis were included. In Japan, low alcohol consumption was consistently associated with substantially reduced incidence and prevalence of hepatic steatosis compared to non-drinkers (RR for <20g pure alcohol/day=0.75, 95% CI: 0.71-0.79, I(2)=0%). No overall association was found in other countries (RR=1.05, 95% CI: 0.86-1.30, I(2)=84%). Dose-response analyses in Japan (up to 80g/day) showed an inverse relationship in men and a J-shape in women. CONCLUSIONS Alcohol consumption showed a complex association with hepatic steatosis with substantial differences by ethnicity and sex. Low alcohol consumption was beneficial in Japan with good epidemiological evidence, whereas there was no association in other countries. However, heterogeneity was large in countries other than Japan. More and higher quality research in diverse ethnic populations is needed to further clarify this relationship.
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Gitto S, Golfieri L, Caputo F, Grandi S, Andreone P. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease. Biomolecules 2016; 6:11. [PMID: 26784248 PMCID: PMC4808805 DOI: 10.3390/biom6010011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 12/16/2015] [Accepted: 12/27/2015] [Indexed: 12/20/2022] Open
Abstract
Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption.
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Affiliation(s)
- Stefano Gitto
- Department of Gastroenterology, Azienda Ospedaliero-Universitaria & University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Lucia Golfieri
- Department of Psychology, University of Bologna, Bologna 40138, Italy.
| | - Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, Cento, Ferrara 44011, Italy.
- "G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Clinical Medicine, University of Bologna, Bologna 40138, Italy.
| | - Silvana Grandi
- Department of Psychology, University of Bologna, Bologna 40138, Italy.
| | - Pietro Andreone
- Department of Medical and Surgical Sciences, University of Bologna and Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Malpighi, Via Massarenti 9, Bologna 40138, Italy.
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Llerena S, Arias-Loste MT, Puente A, Cabezas J, Crespo J, Fábrega E. Binge drinking: Burden of liver disease and beyond. World J Hepatol 2015; 7:2703-2715. [PMID: 26644814 PMCID: PMC4663390 DOI: 10.4254/wjh.v7.i27.2703] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 10/26/2015] [Accepted: 11/11/2015] [Indexed: 02/06/2023] Open
Abstract
The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts (in the form of violence or traffic accidents) and its organic impact (affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.
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In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses. Biomolecules 2015; 5:3280-94. [PMID: 26610587 PMCID: PMC4693278 DOI: 10.3390/biom5043280] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 11/17/2015] [Indexed: 01/06/2023] Open
Abstract
Chronic alcoholics who also binge drink (i.e., acute on chronic) are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4%) for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart). Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9), dually modified phosphoacetylated histone H3 (H3AcK9/PS10), and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10) and H3 ser 28 (H3S28) increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.
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Madrigal-Santillán E, Bautista M, Gayosso-De-Lucio JA, Reyes-Rosales Y, Posadas-Mondragón A, Morales-González &A, Soriano-Ursúa MA, García-Machorro J, Madrigal-Bujaidar E, Álvarez-González I, Morales-González JA. Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration. World J Gastroenterol 2015; 21:7718-7729. [PMID: 26167072 PMCID: PMC4491959 DOI: 10.3748/wjg.v21.i25.7718] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/25/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the effect of an extract of Geranium schiedeanum (Gs) as a hepatoprotective agent against ethanol (EtOH)-induced toxicity in rats. METHODS Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy (PH); they were then divided into three groups (groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups (2-3) drank an aqueous solution of EtOH (40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances (TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed. RESULTS Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration (restitution liver mass: PH-EtOH group 60.68% vs PH-Gs-EtOH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by EtOH administration appeared to be mitigated by the extract, as observed from the TBARs (PH-EtOH group 200.14 mmol/mg vs PH-Gs-EtOH group 54.20 mmol/mg; P < 0.05), total status of antioxidants (PH-EtOH group 1.43 mmol/L vs PH-Gs-EtOH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination (PH-EtOH group 4.80 mg/g vs PH-Gs-EtOH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals. CONCLUSION The administered extract showed a hepatoprotective effect, limiting the EtOH-induced hepatotoxic effects. This effect can be related to modulating oxido-reduction processes.
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