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Enciu VT, Ologeanu PM, Constantinescu A, Fierbinteanu-Braticevici C. Latest Insights in Alcohol-Related Liver Disease and Alcoholic Hepatitis. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2025:rjim-2025-0007. [PMID: 40245287 DOI: 10.2478/rjim-2025-0007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Indexed: 04/19/2025]
Abstract
Alcohol-related liver disease (ALD) is still to this date one of the leading causes of chronic liver disease globally. ALD comprises a wide disease spectrum, from the benign liver steatosis, to the life-threatening inflammatory acute phenotype of alcoholic hepatitis (AH) and ultimately, advanced liver fibrosis and cirrhosis. AH represents an acute inflammatory liver condition caused by prolonged high quantities of alcohol intake. Disease outcome varies from mild to severe, with systemic implication and high mortality. Although the pathogenesis has been extensively studied over the years, little progress has been made regarding therapeutic options. In over 50 years, steroid treatment is still the cornerstone therapeutic option, albeit having multiple limitations and a low success rate. On the other hand, important progress has been made regarding disease management and severity stratification with the implementation of different prognostic score. Although highly prevalent, AH still has many unmet needs, with a growing necessity for novel non-invasive diagnosis, prognosis biomarkers and impactful treatment options.
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Affiliation(s)
- Vlad-Teodor Enciu
- 1Internal Medicine II and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Emergency University Hospital, 050098 Bucharest, Romania
| | - Priscila Madalina Ologeanu
- 1Internal Medicine II and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Emergency University Hospital, 050098 Bucharest, Romania
| | - Alexandru Constantinescu
- 2Emergency University Hospital, 050098 Bucharest, Romania
- 3Internal Medicine I and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474, Bucharest, Romania
| | - Carmen Fierbinteanu-Braticevici
- 1Internal Medicine II and Gastroenterology Department, Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Emergency University Hospital, 050098 Bucharest, Romania
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Zhang N, Li J, Xie X, Hu Y, Chen H, Zhang Y, Liu Y, Zhu X, Xu H, Wang Z, Baima K, Zhang X, Qin Z, Yu Z, Xiao X, Zhao X. Changes in drinking levels and metabolic dysfunction-associated steatotic liver disease: a longitudinal study from the China multi-ethnic cohort study. BMC Public Health 2025; 25:556. [PMID: 39934719 PMCID: PMC11817541 DOI: 10.1186/s12889-025-21752-1] [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: 11/15/2024] [Accepted: 02/03/2025] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Little is known about the associations of changes in drinking levels with the newly defined metabolic dysfunction-associated steatotic liver disease (MASLD). We therefore sought to estimate the associations between changes in drinking levels and MASLD in less developed regions of China. METHODS This longitudinal study included 8727 participants from the China Multi-Ethnic Cohort (CMEC) in less developed regions, all participating in baseline and a follow-up survey. MASLD was defined as hepatic steatosis, along with the presence of at least one of five cardiometabolic risks, in addition to limiting excessive alcohol consumption. We applied the parametric g-formula to evaluate the association between changes in drinking levels and MASLD. We further estimated the association between changes in drinking levels and fibrosis scores (AST-to-platelet ratio and fibrosis-4 index) in patients with MASLD. RESULTS Compared with sustained non-drinking, sustained modest drinking was associated with a higher risk of MASLD (Mean Ratio (MR): 1.127 [95% CI: 1.040-1.242]). Compared to sustained non-drinking, the MR for those transitioning from non-drinking to modest drinking was 1.065 [95% CI: 0.983-1.169], while the MR for those changing from modest drinking to non-drinking was 1.059 [95% CI: 0.965, 1.173]. Non-invasive fibrosis scores tended to increase with modest drinking compared to sustained non-drinking. CONCLUSION In the less developed regions of China, sustained moderate drinking was associated with the risk of MASLD compared with sustained non-drinking. Increased drinking showed a trend towards a higher risk of MASLD. This study can inform drinking policies related to MASLD and liver fibrosis in less developed regions.
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Affiliation(s)
- Ning Zhang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Jingzhong Li
- Tibet Center for Disease Control and Prevention, Lhasa, China
| | - Xiaofen Xie
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yifan Hu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Hongxiang Chen
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yuan Zhang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yujie Liu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Xingren Zhu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Hao Xu
- State Key Laboratory of Oral Diseases, Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences, Sichuan University, Chengdu, China
| | - Zhenghong Wang
- Chongqing Municipal Center for Disease Control and Prevention, Chongqing, China
| | - Kangzhuo Baima
- High Altitude Health Science Research Center of Tibet University, Lhasa, Tibet, China
| | - Xuehui Zhang
- School of Public Health, Kunming Medical University, Kunming, China
| | - Zixiu Qin
- School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China
| | - Zhimiao Yu
- Chengdu Center for Disease Control and Prevention, Chengdu, China
| | - Xiong Xiao
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
| | - Xing Zhao
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
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Vornoli A, Souid A, Lazzari B, Turri F, Pizzi F, Bramanti E, Campanella B, Trouki C, Raffaelli A, Wójcik M, Della Croce CM, Giorgetti L, Longo V, Capra E, Pozzo L. A Moderate Intake of Beer Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a High-Fat Diet (HFD)-Induced Mouse Model. Molecules 2024; 29:5954. [PMID: 39770043 PMCID: PMC11676803 DOI: 10.3390/molecules29245954] [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: 11/05/2024] [Revised: 12/02/2024] [Accepted: 12/12/2024] [Indexed: 01/04/2025] Open
Abstract
Beer and its components show potential for reducing hepatic steatosis in rodent models through multiple mechanisms. This study aimed to evaluate beer's anti-steatotic effects in a high-fat diet (HFD)-induced mouse model of Metabolic dysfunction-Associated Liver Disease (MASLD) and to explore the underlying mechanisms. In the HFD group, steatosis was confirmed by altered blood parameters, weight gain, elevated liver lipid content, and histological changes. These markers were normalized in the HFD+beer group, reaching levels similar to the control (CTR) group. Protein carbonylation and lipid peroxidation levels were consistent across all groups, suggesting that the model represents an early stage of MASLD without oxidative stress. Transcriptomic and CpG methylation analyses revealed clear distinctions between the CTR and HFD groups. RNA sequencing identified 162 differentially expressed genes (DEGs) between the CTR and HFD groups, primarily related to inflammation and lipid regulation. Beer consumption modified the health of the HFD mice, affecting inflammation but not lipid homeostasis (CTR vs. HFD+beer, DEGs = 43). The CpG methylation analysis indicated that beer lowered methylation, impacting genes linked to lipid accumulation and inflammation. A cecal metabolite analysis suggested that beer improved short-chain fatty acid metabolism (SCFA). In summary, a moderate beer intake may mitigate MASLD by modulating lipid metabolism and SCFA pathways, likely through polyphenol activity.
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Affiliation(s)
- Andrea Vornoli
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
| | - Aymen Souid
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
| | - Barbara Lazzari
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Corti 12, 20133 Milan, Italy;
| | - Federica Turri
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via dell’Università 6, 26900 Lodi, Italy; (F.T.); (F.P.)
| | - Flavia Pizzi
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via dell’Università 6, 26900 Lodi, Italy; (F.T.); (F.P.)
| | - Emilia Bramanti
- Institute of Chemistry of Organometallic Compounds, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (E.B.); (B.C.)
| | - Beatrice Campanella
- Institute of Chemistry of Organometallic Compounds, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (E.B.); (B.C.)
| | - Cheherazade Trouki
- Institute for Chemical and Physical Processes, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy;
- Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy
| | - Andrea Raffaelli
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
- Crop Science Research Center, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy
| | - Marta Wójcik
- Sub-Department of Pathophysiology, Department of Preclinical of Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Akademicka 12, 20-033 Lublin, Poland;
| | - Clara Maria Della Croce
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
| | - Lucia Giorgetti
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
| | - Vincenzo Longo
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
| | - Emanuele Capra
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via dell’Università 6, 26900 Lodi, Italy; (F.T.); (F.P.)
| | - Luisa Pozzo
- Institute of Agricultural Biology and Biotechnology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy; (A.V.); (A.S.); (A.R.); (L.G.); (V.L.)
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Xue H, Wang L, Wu Y, Liu X, Jiang J, Chan SO, Chen X, Ling W, Yu C. Association of moderate alcohol intake with the risks of cirrhosis and steatotic liver disease: Results from a large population-based cohort study. Clin Nutr 2024; 43:75-83. [PMID: 39427474 DOI: 10.1016/j.clnu.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/02/2024] [Accepted: 10/07/2024] [Indexed: 10/22/2024]
Abstract
BACKGROUND&AIMS There is uncertainty about the associations between moderate alcohol consumption and liver-related outcomes. We aimed to explore the associations of moderate drinking with cirrhosis, steatotic liver disease (SLD), and liver cancer in a large cohort study. METHODS A total of 215,559 non-drinkers and moderate drinkers (<20 g/day alcohol for females or < 30 g/day for males) were enrolled between 2006 and 2010 and followed up to 2022. The primary outcome is incident cirrhosis, and the secondary outcomes are the incidence of steatotic liver disease and liver cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were calculated for liver-related outcomes in relation to moderate drinkers, as well as the quantity and type of their alcohol intake. All analyses were stratified by sex. RESULTS A total of 705 cirrhosis, 2010 SLD, and 350 liver cancer cases were documented during a median follow-up period of 12.7 years. Compared with non-drinkers, moderate drinkers had a lower risk of SLD (HR: 0.77; 95 % CI: 0.66, 0.89). Among the moderate drinkers, alcohol intake [per standard deviation (SD) increment] was associated with an increased risk of incident cirrhosis (HR: 1.11; 95 % CI: 1.02, 1.20), but the association was attenuated after restricting alcohol intake to no more than 16 g/day. Wine consumption (per SD increment of the percentage of wine consumption of total alcohol intake) had an inverse association with incident cirrhosis and SLD (HR: 0.82; 95 % CI: 0.75, 0.89 for cirrhosis; HR: 0.91; 95 % CI: 0.87, 0.96 for SLD). The inverse associations between moderate wine use and SLD were likely to be sex-dependent (P for interaction = 0.01). CONCLUSIONS The excessive alcohol threshold of 30 g/day for males may be set high for liver health. Further work is needed to make sex-specific recommendations on moderate drinking for liver health.
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Affiliation(s)
- Hongliang Xue
- Department of Nutrition, School of Public Health, Guangzhou Medical University, Guangzhou, China; The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Liqing Wang
- Department of Neurology, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yuankai Wu
- Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xinyu Liu
- Department of Nutrition, School of Public Health, Guangzhou Medical University, Guangzhou, China
| | - Jingcheng Jiang
- Department of Intergrative Physiology, University of Colorado, Boulder, USA
| | - Sun On Chan
- School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
| | - Xu Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, USA; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China.
| | - Chao Yu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China; Medical Examination Center, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Ting PS, Lin WT, Liangpunsakul S, Novack M, Huang CK, Lin HY, Tseng TS, Chen PH. Convergence of Alcohol Consumption and Dietary Quality in US Adults Who Currently Drink Alcohol: An Analysis of Two Core Risk Factors of Liver Disease. Nutrients 2024; 16:3866. [PMID: 39599652 PMCID: PMC11597591 DOI: 10.3390/nu16223866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/19/2024] [Accepted: 10/24/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES Alcohol consumption and poor dietary habits are on the rise in the United States, posing significant challenges to public health due to their contribution to chronic diseases such as liver failure. While associations between alcohol consumption patterns and diet quality have been explored, the relationship between specific alcoholic beverage types and diet quality remains underexamined. This study aims to compare diet quality among consumers of different alcoholic beverage types. METHODS We conducted a cross-sectional analysis of 1917 current alcohol drinkers from the National Health and Nutrition Examination Survey (NHANES) who completed a 24 h dietary recall survey. Diet quality was assessed using the Healthy Eating Index (HEI), with higher scores indicating superior diet quality. Multivariable logistic regression models were employed to assess differences in HEI between consumers of various alcoholic beverage types, using wine-only drinkers as the reference group and controlling for demographic, socioeconomic, lifestyle, and metabolic syndrome variables. RESULTS Beer-only drinkers were more likely to have lower income, higher rates of cigarette smoking, and insufficient physical activity compared to other alcohol consumers. In the fully adjusted multivariable model, beer-only drinkers had an HEI score that was 3.12 points lower than wine-only drinkers. In contrast, liquor/cocktail-only and multiple-type drinkers had similar HEI scores to wine-only drinkers. CONCLUSIONS Beer-only consumption is associated with poorer diet quality among alcohol drinkers. Targeted patient education and public health campaigns may be effective in addressing the combined impact of alcohol consumption and poor diet quality on chronic disease risk.
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Affiliation(s)
- Peng-Sheng Ting
- Division of Gastroenterology and Hepatology, Tulane University School of Medicine, 131 S. Robertson St., New Orleans, LA 70112, USA;
- University Medical Center, 2000 Canal St., New Orleans, LA 70112, USA
| | - Wei-Ting Lin
- Social, Behavioral, and Population Sciences, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, New Orleans, LA 70112, USA
| | - Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA
- Roudebush Veterans Administration Medical Center, 1481 W. 10th Street, Indianapolis, IN 46202, USA
| | - Madeline Novack
- Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA
| | - Chiung-Kuei Huang
- Department of Pathology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA
| | - Hui-Yi Lin
- School of Public Health, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112, USA
| | - Tung-Sung Tseng
- School of Public Health, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, 4th Floor, Baltimore, MD 21287, USA
- Division of Addiction Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, 4th Floor, Baltimore, MD 21287, USA
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Verma N, Vinod AP, Singal AK. The pharmacological management of alcohol-related cirrhosis: what's new? Expert Opin Pharmacother 2024; 25:1923-1941. [PMID: 39360770 DOI: 10.1080/14656566.2024.2409941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 09/24/2024] [Indexed: 10/05/2024]
Abstract
INTRODUCTION Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies. AREAS COVERED This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD. EXPERT OPINION Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.
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Affiliation(s)
- Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwin P Vinod
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani K Singal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Louisville School of Medicine, Louisville, KY, USA
- Department of Transplant Hepatology, Jewish Hospital and Trager Transplant Center, Louisville, Kentucky, USA
- Department of Research, Veteran Affairs Medical Center, Sioux Falls, SD, USA
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Ting PS, Lin WT, Huang CK, Lin HY, Tseng TS, Chen PH. Exclusive liquor and cocktail consumption is associated with at-risk fibrosis among nonheavy alcohol users with metabolic dysfunction-associated steatotic liver disease. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:88-97. [PMID: 38206286 PMCID: PMC10786214 DOI: 10.1111/acer.15220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/28/2023] [Accepted: 10/30/2023] [Indexed: 01/12/2024]
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol consumption have both increased in recent years, and there is debate as to whether nonheavy alcohol use is safe in MASLD. We analyzed the association between different nonheavy alcohol use patterns and at-risk liver fibrosis among individuals with MASLD. METHODS We conducted a cross-sectional study of 1072 eligible National Health and Nutrition Examination Survey participants with MASLD who reported nonheavy alcohol consumption. We used vibration-controlled transient elastography to define the primary outcome of at-risk liver fibrosis as >8.2 kPa (stage F2-F4). Multivariable logistic regression models were used to determine the association of different alcohol consumption patterns (average drinks/day, drinking days/week, weekly alcohol intake, type of alcoholic beverage) and at-risk hepatic fibrosis, controlling for demographic/socioeconomic, lifestyle/dietary, and metabolic risk factors. RESULTS Exclusive liquor or cocktail drinkers had a 5.02-fold odds of at-risk fibrosis (95% CI: 1.15-21.95) compared with non-drinkers when controlling for potential confounders. While consuming an average of 2 drinks/day, ≥3 drinking days/week, or 1-3 drinks/week appeared to have a lower association with at-risk fibrosis when controlling for demographic/socioeconomic risk factors, the association was not present after controlling for lifestyle/dietary and metabolic risk factors. CONCLUSIONS There is an association between exclusive liquor/cocktail consumption and at-risk liver fibrosis in patients with MASLD who report nonheavy alcohol consumption.
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Affiliation(s)
- Peng-sheng Ting
- Division of Gastroenterology and Hepatology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA
| | - Wei-Ting Lin
- Social, Behavioral, and Population Sciences, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, New Orleans, LA 70112, USA
| | - Chiung-Kuei Huang
- Department of Pathology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA
| | - Hui-Yi Lin
- School of Public Health, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112, USA
| | - Tung-Sung Tseng
- School of Public Health, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, 4 Floor, Baltimore, MD 21287, USA
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Jophlin LL, Singal AK, Bataller R, Wong RJ, Sauer BG, Terrault NA, Shah VH. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol 2024; 119:30-54. [PMID: 38174913 PMCID: PMC11040545 DOI: 10.14309/ajg.0000000000002572] [Citation(s) in RCA: 54] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 10/04/2023] [Indexed: 01/05/2024]
Abstract
ABSTRACT Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.
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Affiliation(s)
- Loretta L. Jophlin
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville Health, Louisville, Kentucky, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Sioux Falls, South Dakota, USA
| | - Ramon Bataller
- Liver Unit, Department of Digestive and Metabolic Diseases, Hospital Clinic, Barcelona, Spain
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | - Bryan G. Sauer
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Minea H, Singeap AM, Sfarti CV, Girleanu I, Chiriac S, Muzica C, Cuciureanu T, Petrea OC, Huiban L, Zenovia S, Nastasa R, Rotaru A, Stafie R, Stratina E, Cojocariu C, Stanciu C, Trifan A. The Impact of Alcohol Consumption Pattern on Liver Fibrosis in Asymptomatic Patients. J Clin Med 2023; 12:7405. [PMID: 38068457 PMCID: PMC10706981 DOI: 10.3390/jcm12237405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 01/05/2025] Open
Abstract
INTRODUCTION Alcohol consumption (AC) represents a widespread cause of liver diseases affecting 10-20% of the population. The study aimed to evaluate the relationship between advanced liver fibrosis (ALF) measured by transient elastography (TE), laboratory parameters, and the amount of AC depending on non-modifiable risk factors such as age and gender. METHODS We examined 689 patients with an average age of 49.32 ± 14.31 years, 72.9% males, without liver pathology, who admitted a moderate/high consumption (female ≤ 7 versus > 7 drinks/week; male ≤ 14 versus > 14 drinks/week) for at least five years. The fibrosis level was adjusted according to transaminase levels. Predictive factors were established using univariate regression analysis. RESULTS ALF (≥F3) was detected in 19.30% of subjects, predominantly males (14.1%) and patients over 55 years (12.5%). Excessive consumption of distilled spirits is associated with ALF in females (OR = 4.5), males (OR = 6.43) and patients over 55 years (OR = 3.73). A particularity highlighted in both genders, regardless of the age group, was the negative correlation between the decrease in the number of platelets, the albumin concentration, and the appearance of AFL. CONCLUSIONS Screening using TE represents an approach for early detection of ALF in asymptomatic populations and the development of a risk stratification scheme.
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Affiliation(s)
- Horia Minea
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Catalin Victor Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Oana Cristina Petrea
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (H.M.); (C.M.); (T.C.); (L.H.); (S.Z.); (R.N.); (A.R.); (R.S.); (E.S.); (C.C.); (C.S.); (A.T.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
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Wojtowicz JS. Long-Term Health Outcomes of Regular, Moderate Red Wine Consumption. Cureus 2023; 15:e46786. [PMID: 37954791 PMCID: PMC10634232 DOI: 10.7759/cureus.46786] [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] [Accepted: 10/09/2023] [Indexed: 11/14/2023] Open
Abstract
Studies that are conducted to assess alcohol's long-term health outcomes generally report the results as a pooled analysis across all types of alcohol. Questions have been raised regarding potential health differences between types of alcohol, such as beer, wine, or spirits. While these three share the same alcohol in the form of ethanol, they differ in the other compounds they contain that are particular to each type of alcohol, specifically the polyphenols in red wine. The generalizability of pooled results may be limited due to the differences in health outcomes that may exist between different types of alcohol and lead to overall conclusions that differ from the subset analysis by type of alcohol that is often reported in the data tables of an article. The objective of this systematic review was to specifically address the assessment of the long-term health outcomes of regular, moderate, red wine consumption. PubMed was searched from 1987 through June 2023. Studies were included if they met all the following criteria: adult participants, red wine consumption and its frequency (close to daily), volume in moderation (1 glass/day for women, 2 glasses/day for men), and measurement of long-term (> 2 years) health outcomes. Nonclinical animal studies, or studies with an endpoint as a marker or biomarker, without a health outcome, of short duration (< 2 years), small size (< 25 subjects), a focus on binge drinking, no wine analysis performed, review articles, meta-analysis, or editorial/commentary were excluded. A total of 74 studies met the inclusion/exclusion criteria. Of these, 27 (36%) evaluated cancer outcomes, 14 (19%) evaluated cardiovascular outcomes, 10 (14%) evaluated mortality, 7 (9%) evaluated weight gain, 5 (7%) evaluated dementia, and the remaining 11 evaluated a variety of health outcomes. There were no studies that demonstrated an association between red wine consumption and negative health outcomes. Forty-seven studies demonstrated an association between red wine consumption and positive health outcomes, whereas 26 studies were neutral, and one had mixed results where women had a positive health outcome and men were neutral. All studies on mortality and dementia showed positive health outcomes. From this systematic review of the literature, there is no evidence of an association between moderate red wine consumption and negative health outcomes. Across the various outcomes assessed, a beneficial effect of moderate red wine consumption was consistently seen for mortality and dementia, along with certain cancers (e.g., non-Hodgkin lymphoma) and cardiovascular conditions (e.g., metabolic syndrome). For other health outcomes, the association was neutral, i.e., neither harmful nor beneficial. This review is not intended to encourage red wine consumption for health outcomes but rather to avoid discouraging moderate red wine consumption based on misunderstanding or misinterpretation of the red wine data due to the reporting of pooled data across all types of alcohol.
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Seitz HK, Moreira B, Neuman MG. Pathogenesis of Alcoholic Fatty Liver a Narrative Review. Life (Basel) 2023; 13:1662. [PMID: 37629519 PMCID: PMC10455719 DOI: 10.3390/life13081662] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/12/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
Alcohol effect hepatic lipid metabolism through various mechanisms, leading synergistically to an accumulation of fatty acids (FA) and triglycerides. Obesity, as well as dietary fat (saturated fatty acids (FA) versus poly-unsaturated fatty acids (PUFA)) may modulate the hepatic fat. Alcohol inhibits adenosine monophosphate activated kinase (AMPK). AMPK activates peroxisome proliferator activated receptor a (PPARα) and leads to a decreased activation of sterol regulatory element binding protein 1c (SRABP1c). The inhibition of AMPK, and thus of PPARα, results in an inhibition of FA oxidation. This ß-oxidation is further reduced due to mitochondrial damage induced through cytochrome P4502E1 (CYP2E1)-driven oxidative stress. Furthermore, the synthesis of FAs is stimulated through an activation of SHREP1. In addition, alcohol consumption leads to a reduced production of adiponectin in adipocytes due to oxidative stress and to an increased mobilization of FAs from adipose tissue and from the gut as chylomicrons. On the other side, the secretion of FAs via very-low-density lipoproteins (VLDL) from the liver is inhibited by alcohol. Alcohol also affects signal pathways such as early growth response 1 (Egr-1) associated with the expression of tumour necrosis factor α (TNF α), and the mammalian target of rapamycin (mTOR) a key regulator of autophagy. Both have influence the pathogenesis of alcoholic fatty liver. Alcohol-induced gut dysbiosis contributes to the severity of ALD by increasing the metabolism of ethanol in the gut and promoting intestinal dysfunction. Moreover, pathogen-associated molecular patterns (PAMPS) via specific Toll-like receptor (TLR) bacterial overgrowth leads to the translocation of bacteria. Endotoxins and toxic ethanol metabolites enter the enterohepatic circulation, reaching the liver and inducing the activation of the nuclear factor kappa-B (NFκB) pathway. Pro-inflammatory cytokines released in the process contribute to inflammation and fibrosis. In addition, cellular apoptosis is inhibited in favour of necrosis.
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Affiliation(s)
- Helmut K. Seitz
- Centre of Liver and Alcohol Associated Diseases, Ethianum Clinic, Faculty of Medicine, University of Heidelberg, 69120 Heidelberg, Germany;
| | - Bernardo Moreira
- Centre of Liver and Alcohol Associated Diseases, Ethianum Clinic, Faculty of Medicine, University of Heidelberg, 69120 Heidelberg, Germany;
| | - Manuela G. Neuman
- In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Banting Institute, Toronto, ON M5G 1L5, Canada;
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12
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Staufer K, Stauber RE. Steatotic Liver Disease: Metabolic Dysfunction, Alcohol, or Both? Biomedicines 2023; 11:2108. [PMID: 37626604 PMCID: PMC10452742 DOI: 10.3390/biomedicines11082108] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 07/19/2023] [Accepted: 07/20/2023] [Indexed: 08/27/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), both of them accounting for fatty liver disease (FLD), are among the most common chronic liver diseases globally, contributing to substantial public health burden. Both NAFLD and ALD share a similar picture of clinical presentation yet may have differences in prognosis and treatment, which renders early and accurate diagnosis difficult but necessary. While NAFLD is the fastest increasing chronic liver disease, the prevalence of ALD has seemingly remained stable in recent years. Lately, the term steatotic liver disease (SLD) has been introduced, replacing FLD to reduce stigma. SLD represents an overarching term to primarily comprise metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as alcohol-related liver disease (ALD), and MetALD, defined as a continuum across which the contribution of MASLD and ALD varies. The present review discusses current knowledge on common denominators of NAFLD/MASLD and ALD in order to highlight clinical and research needs to improve our understanding of SLD.
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Affiliation(s)
- Katharina Staufer
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Rudolf E Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria
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13
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Zhou Y, Hua J, Huang Z. Effects of beer, wine, and baijiu consumption on non-alcoholic fatty liver disease: Potential implications of the flavor compounds in the alcoholic beverages. Front Nutr 2023; 9:1022977. [PMID: 36687705 PMCID: PMC9852916 DOI: 10.3389/fnut.2022.1022977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 12/07/2022] [Indexed: 01/09/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and its global incidence is estimated to be 24%. Beer, wine, and Chinese baijiu have been consumed worldwide including by the NAFLD population. A better understanding of the effects of these alcoholic beverages on NAFLD would potentially improve management of patients with NAFLD and reduce the risks for progression to fibrosis, cirrhosis, and hepatocellular carcinoma. There is evidence suggesting some positive effects, such as the antioxidative effects of bioactive flavor compounds in beer, wine, and baijiu. These effects could potentially counteract the oxidative stress caused by the metabolism of ethanol contained in the beverages. In the current review, the aim is to evaluate and discuss the current human-based and laboratory-based study evidence of effects on hepatic lipid metabolism and NAFLD from ingested ethanol, the polyphenols in beer and wine, and the bioactive flavor compounds in baijiu, and their potential mechanism. It is concluded that for the potential beneficial effects of wine and beer on NAFLD, inconsistence and contrasting data exist suggesting the need for further studies. There is insufficient baijiu specific human-based study for the effects on NAFLD. Although laboratory-based studies on baijiu showed the antioxidative effects of the bioactive flavor compounds on the liver, it remains elusive whether the antioxidative effect from the relatively low abundance of the bioactivate compounds could outweigh the oxidative stress and toxic effects from the ethanol component of the beverages.
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Affiliation(s)
- Yabin Zhou
- School of Biological Engineering, Sichuan University of Science and Engineering (SUSE), Zigong, Sichuan, China,Liquor-Making Biotechnology and Application Key Laboratory of Sichuan Province, Sichuan University of Science and Engineering (SUSE), Zigong, Sichuan, China,College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Jin Hua
- School of Biological Engineering, Sichuan University of Science and Engineering (SUSE), Zigong, Sichuan, China,College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia
| | - Zhiguo Huang
- School of Biological Engineering, Sichuan University of Science and Engineering (SUSE), Zigong, Sichuan, China,Liquor-Making Biotechnology and Application Key Laboratory of Sichuan Province, Sichuan University of Science and Engineering (SUSE), Zigong, Sichuan, China,*Correspondence: Zhiguo Huang,
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Zhang R, Tang Z, Xu W, Ding Y, Zhang M, Guan Q, Jiang R, Chen Y, Hua Y, Wang J. Risk factors and protective factors for alcohol-related liver disease: A systematic review and meta-analysis. Alcohol Clin Exp Res 2022; 46:2128-2136. [PMID: 36203342 DOI: 10.1111/acer.14951] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/14/2022] [Accepted: 09/22/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Although alcohol-related liver disease (ALD) is a global health threat, there are no specific effective treatments for it. Thus, efforts at preventing ALD are important and could be enhanced by using strategies based on validated risk and protective factors for the disease. METHODS The literature on factors influencing the risk for ALD was systematically searched from PubMed, Embase, and the Cochrane library databases from inception to June 2022. Factors suitable for quantitative analysis were submitted to meta-analysis using fixed-effects and random-effects models to calculate each factor's risk ratio (RR) and 95% confidence interval (CI). RESULTS Ten cohort studies (covering 1,005,339 subjects) that reported a clear causal relationship were included in the analysis, involving 11 potential risk factors (sex, race, education level, body mass index, alcohol consumption, types of alcoholic beverage, duration of drinking, drinking frequency, smoking, coffee consumption, and tea consumption). Three of these factors (sex, alcohol consumption, and smoking) were subjected to meta-analysis, and the results showed that male sex (RR = 2.84, 95% CI = 1.86-4.36), alcohol consumption ≥280 g/week (RR = 4.96, 95% CI = 2.71-9.07), and smoking (RR = 2.39, 95% CI = 1.97-2.89) were risk factors for ALD. CONCLUSIONS Many factors are likely to influence the incidence of ALD, and male sex, heavy alcohol consumption, and smoking increase the risk of ALD. The relationship between other factors and ALD risk needs further evaluation.
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Affiliation(s)
- Ru Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Zongzhe Tang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Wenjie Xu
- Shanghai Pudong New Area Heqing Community Health Service Center, Shanghai, China
| | - Yajie Ding
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Mengting Zhang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Qing Guan
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Rong Jiang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Yue Chen
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
| | - Yingxue Hua
- Shanghai Pudong New Area Heqing Community Health Service Center, Shanghai, China
| | - Jie Wang
- Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China
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Falamarzi K, Malekpour M, Tafti MF, Azarpira N, Behboodi M, Zarei M. The role of FGF21 and its analogs on liver associated diseases. Front Med (Lausanne) 2022; 9:967375. [PMID: 36457562 PMCID: PMC9705724 DOI: 10.3389/fmed.2022.967375] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 09/12/2022] [Indexed: 07/25/2023] Open
Abstract
Fibroblast growth factor 21 (FGF21), a member of fibroblast growth factor family, is a hormone-like growth factor that is synthesized mainly in the liver and adipose tissue. FGF21 regulates lipid and glucose metabolism and has substantial roles in decreasing lipogenesis and increasing hepatic insulin sensitivity which causing lipid profile improvement. FGF21 genetic variations also affect nutritional and addictive behaviors such as smoking and alcohol consumption and eating sweets. The role of FGF21 in metabolic associated diseases like diabetes mellitus had been confirmed previously. Recently, several studies have demonstrated a correlation between FGF21 and liver diseases. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease worldwide. NAFLD has a wide range from simple steatosis to steatohepatitis with or without fibrosis and cirrhosis. Elevated serum levels of FGF21 associated with NAFLD and its pathogenesis. Alcoholic fatty liver disease (AFLD), another condition that cause liver injury, significantly increased FGF21 levels as a protective factor; FGF21 can reverse the progression of AFLD and can be a potential therapeutic agent for it. Also, NAFLD and AFLD are the most important risk factors for hepatocellular carcinoma (HCC) which is the fourth deadliest cancer in the world. Several studies showed that lack of FGF21 induced oncogenic condition and worsened HCC. In this review article, we intend to discuss different aspects of FGF21 in NAFLD, AFLD and HCC; including the role of FGF21 in pathophysiology of these conditions, the effects of FGF21 mutations, the possible use of the FGF21 as a biomarker in different stages of these diseases, as well as the usage of FGF21 and its analog molecules in the treatment of these diseases.
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Affiliation(s)
- Kimia Falamarzi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahdi Malekpour
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mobin Fallah Tafti
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehrdad Behboodi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Zarei
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- John B. Little Center for Radiation Sciences, Harvard T. H. Chan School of Public Health, Boston, MA, United States
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Clinical and Safety Evaluation of Liv.52 in Alcoholic Liver Disease: A Review. GASTROENTEROLOGY INSIGHTS 2022. [DOI: 10.3390/gastroent13040037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Alcoholic liver disease (ALD) has been a growing concern in developed and developing nations. Oxidative stress and lipid peroxidation are the most common cause of the development and progression of ALD. Due to paucity in the number and efficacy of hepatoprotective drugs currently available, and with the easy availability of natural therapy and herbal medicines, ALD is managed using a combination of pharmaceutical interventions and herbal medications. However, the effectiveness of these hepatoprotectives is controversial. Preclinical and clinical studies have demonstrated that Liv.52 modulates the lipotropic activity of hepatocytes, reduces inflammation, enhances alcohol and acetaldehyde metabolism, and protects the hepatic parenchyma by restoring the antioxidant levels of hepatocytes. Clinical studies further support that there is improvement in the subjective symptoms of patients as well as improvements in liver function test parameters. Studies suggest that Liv.52 is well tolerated and has no reported side effects.
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Liu Z, Song C, Suo C, Fan H, Zhang T, Jin L, Chen X. Alcohol consumption and hepatocellular carcinoma: novel insights from a prospective cohort study and nonlinear Mendelian randomization analysis. BMC Med 2022; 20:413. [PMID: 36303185 PMCID: PMC9615332 DOI: 10.1186/s12916-022-02622-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 10/21/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Heavy drinking was well associated with an increased risk of hepatocellular carcinoma (HCC), whereas the effect of low-to-moderate drinking on HCC remains under debate. METHODS Participants from the UK Biobank with detailed information on alcohol use and free of common diseases were included. Daily pure alcohol intake (g/day) was calculated, and the predominant alcoholic beverage type was assigned for each participant. Additive Cox regression model and nonlinear Mendelian randomization (NLMR) analyses were performed to evaluate the association of alcohol intake with HCC. RESULTS Of 329,164 participants (52.3% females, mean [SD] age = 56.7 [8.0] years), 201 incident HCC cases were recorded during the median follow-up of 12.6 years. The best-fitted Cox regression model suggested a J-shaped relationship between daily alcohol intake level and HCC risk. However, NLMR analysis did not detect a nonlinear correlation between alcohol use and HCC (nonlinearity P-value: 0.386). The J-shaped correlation pattern was detected only in subjects who mainly drank wine but not in those who mainly drank beer, spirits, or fortified wine. Moderate wine drinking showed a significant alanine transaminase (ALT)- and aspartate aminotransferase-lowering effect compared to that of the nondrinkers. In low-risk populations of HCC including women, people aged < 60 years, subjects with normal ALT levels, and those carrying non-risk genotypes of PNPLA3 rs738409 and TM6SF2 rs58542926, we observed a J-shaped correlation between alcohol use and HCC; however, a positive dose-response correlation was found in their respective counterparts, even in those predominantly drinking wine. CONCLUSIONS Low-to-moderate drinking may be inversely associated with the risk of HCC in low-risk populations, which may be largely driven by wine drinking. However, those in high-risk populations of HCC, such as men and older people, and those with abnormal ALT levels and carry genetic risk variants, should abstain from drinking alcohol. Given the small HCC case number, further validations with larger case numbers are warranted in future works.
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Affiliation(s)
- Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200438, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, 225316, China
| | - Ci Song
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Chen Suo
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, 200032, China.,Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Hong Fan
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, 200032, China.,Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Tiejun Zhang
- Key Laboratory of Public Health Safety, Fudan University, Ministry of Education, Shanghai, 200032, China. .,Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China.
| | - Li Jin
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200438, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, 225316, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200438, China. .,Fudan University Taizhou Institute of Health Sciences, Taizhou, 225316, China. .,National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
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18
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Llamosas-Falcón L, Probst C, Buckley C, Jiang H, Lasserre AM, Puka K, Tran A, Rehm J. Sex-specific association between alcohol consumption and liver cirrhosis: An updated systematic review and meta-analysis. FRONTIERS IN GASTROENTEROLOGY (LAUSANNE, SWITZERLAND) 2022; 1:1005729. [PMID: 36926309 PMCID: PMC10016085 DOI: 10.3389/fgstr.2022.1005729] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Different studies have shown that females develop liver diseases at lower levels of alcohol consumption than males. Our aim was to quantify the dose-response relationship between alcohol consumption and the risk of liver cirrhosis by sex and identify the differences between females and males. A systematic review was conducted using PubMed/Medline and Embase to identify longitudinal and case-control studies that analyzed the relationship between the level of alcohol use and liver cirrhosis (LC) incidence, and mortality (ICD-8 and ICD-9 codes 571 and ICD-10 codes K70, K73, K74). Pooled relative risks (RR) were calculated by random effects models. Restricted cubic splines were used to model the dose-response relationship. A total of 24 studies were included in the analysis. There were collectively 2,112,476 females and 924,853 males, and a total of 4,301 and 4,231 cases of LC for females and males, respectively. We identified a non-linear dose-response relationship. Females showed a higher risk for LC compared to males with the same amount of alcohol consumed daily. For instance, drinking 40 g/day showed RRs of 9.35 (95% CI 7.64-11.45) in females and 2.82 (95% CI 2.53-3.14) in males, while drinking 80 g/day presented RRs of 23.32 (95% CI 18.24-29.82) in females and 7.93 (95% CI 7.12-8.83) in males. Additional analyses showed that a higher risk for females was found for morbidity and for mortality. Understanding the influence of sex on the association of alcohol consumption and the risk of LC is needed to develop recommendations and clinical guidelines for prevention and treatment. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299680, identifier CRD42022299680.
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Affiliation(s)
- Laura Llamosas-Falcón
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Charlotte Probst
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Heidelberg Institute of Global Health, Medical Faculty and University Hospital, Heidelberg, Germany
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Charlotte Buckley
- Department of Automatic Control and Systems Engineering, University of Sheffield, Sheffield, United Kingdom
| | - Huan Jiang
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Aurélie M. Lasserre
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Addiction Medicine, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland
| | - Klajdi Puka
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - Alexander Tran
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Jürgen Rehm
- Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- Institute of Clinical Psychology and Psychotherapy & Center of Clinical Epidemiology and Longitudinal Studies (CELOS), Technische Universität Dresden, Dresden, Germany
- Center for Interdisciplinary Addiction Research (ZIS), Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation, Russia
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19
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Roy N, Nadda N, Kumar H, Prasad C, Kumar Jha J, Pandey HC, Vanamail P, Saraya A, Balhara YPS, Shalimar, Nayak B. Pattern recognition receptor CD14 gene polymorphisms in alcohol use disorder patients and its Influence on liver disease susceptibility. Front Immunol 2022; 13:975027. [PMID: 36238273 PMCID: PMC9551314 DOI: 10.3389/fimmu.2022.975027] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/15/2022] [Indexed: 11/13/2022] Open
Abstract
Background Alcohol use disorders (AUDs) leading to liver disease is major concern over other spectrum of disorder. Excessive alcohol consumption resulting in leaky gut syndrome is attributed to alcohol-induced liver injury through portal translocation of bacterial endotoxin. Susceptibility to alcoholic liver disease (ALD) in AUD patients could be dependent upon genes responsible for inflammation and alcohol metabolism. The pattern recognition receptor CD14 gene is a major player in endotoxin-mediated inflammation and susceptibility to ALD. This study investigated the genetic association of CD14 polymorphisms and other mechanisms relevant to altered inflammatory responses leading to ALD. Methods Patients with alcohol use disorder with ALD (n = 128) and without liver disease (ALC, n = 184) and controls without alcohol use disorder (NALC, n = 152) from North India were enrolled. The CD4 gene polymorphisms in the North Indian population were evaluated by RFLP and sequencing. Secretory CD14 (sCD14), LBP, TLR4, MD2, TNFα, IL1b, IFNγ, IL6, IL10, and IL4 levels in serum were measured by ELISA among groups. The influence of polymorphisms on CD14 gene promoter activity and circulatory bacterial DNA level was determined. Results The CD14 gene promoter and exonic region SNPs were found to be monomorphic, except for SNP rs2569190 for the North Indian population. The genetic association of SNP rs2569190(C/T) with the risk of developing ALD was found significant for TT genotype [ORTT, 95% CI = 2.19, 1.16–4.13 for ALD vs. ALC and OR, 2.09, 1.18–3.72 for ALD vs. NALC]. An increased sCD14 level was observed in AUD patients compared to NALC control. Increased levels of LBP, TLR4, TNFα, IL1β, IFNγ, and IL6 and reduced levels of MD2, IL10, and IL4 were observed among the ALD patients compared to the other two control groups. Elevated levels of pro-inflammatory and reduced levels of anti-inflammatory cytokines were observed in the risk genotype TT groups of ALD patients and the ALC group compared to NALC. Promoter activity was observed in the intronic region flanking SNPs and risk genotype can influence reporter activity, indicating CD14 gene expression. Conclusion Enhanced CD14 expression associated with inflammatory responses increases susceptibility to ALD in the TT genotype of AUD patients.
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20
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Korkmaz D, Konya P, Demirtürk N. Investigation of the Characteristics of Crimean Congo Hemorrhagic Fever Cases Reported in Afyonkarahisar Province. TURKIYE PARAZITOLOJII DERGISI 2022; 46:224-227. [PMID: 36094125 DOI: 10.4274/tpd.galenos.2022.14633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
OBJECTIVE Crimean Congo Hemorrhagic Fever (CCHF); fever, widespread pain in the body, deterioration in liver function tests; it is a tick-borne viral infectious disease that can cause bleeding and death in the skin, mucous membranes, and sometimes internal organs. In this study, we retrospectively evaluated the clinical, laboratory, and epidemiological characteristics of CCHF cases diagnosed in Afyonkarahisar. METHODS Demographic and clinical characteristics, laboratory findings, treatments, and prognoses of patients diagnosed with CCHF in Afyonkarahisar were retrospectively analyzed. RESULTS In Afyonkarahisar, it was determined that 35 case reports were made between 2002 and November 2019, the date when the CCHF was first seen in Turkey. A history of tick attachment was detected in 31 subjects. Tick arrest cases were most common in June (12 cases; 34.3%) and July (9 cases; 2.9%). There was a history of living in rural areas in twenty-seven (77.1%) patients, close contact with animals in 12 patients, and a history of contact with animal blood in 4 patients. All the 35 cases that followed resulted in healing and no mortality was observed. CONCLUSION CCHF is an endemic disease that still maintains its importance in our country. The most important factor in the control with the disease is to prevent virus contact to prevent transmission. People living in endemic areas should be informed about the precautions to be taken against tick bites, and awareness should be raised by providing education about the disease.
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Affiliation(s)
- Derya Korkmaz
- Afyonkarahisar Sağlık Bilimleri Üniversitesi, Sağlık Uygulama ve Araştırma Merkezi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Afyonkarahisar, Türkiye
| | - Petek Konya
- Afyonkarahisar Sağlık Bilimleri Üniversitesi, Sağlık Uygulama ve Araştırma Merkezi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Afyonkarahisar, Türkiye
| | - Neşe Demirtürk
- Afyonkarahisar Sağlık Bilimleri Üniversitesi, Sağlık Uygulama ve Araştırma Merkezi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Afyonkarahisar, Türkiye
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21
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Ferri S, Stefanini B, Mulazzani L, Alvisi M, Tovoli F, Leoni S, Muratori L, Lotti T, Granito A, Bolondi L, Piscaglia F. Very Low Alcohol Consumption Is Associated with Lower Prevalence of Cirrhosis and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease. Nutrients 2022; 14:2493. [PMID: 35745223 PMCID: PMC9231078 DOI: 10.3390/nu14122493] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 06/06/2022] [Accepted: 06/09/2022] [Indexed: 02/04/2023] Open
Abstract
The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients.
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Affiliation(s)
- Silvia Ferri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
| | - Bernardo Stefanini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Lorenzo Mulazzani
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Margherita Alvisi
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Simona Leoni
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
| | - Luca Muratori
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Tommaso Lotti
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Luigi Bolondi
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (B.S.); (L.M.); (M.A.); (F.T.); (S.L.); (L.M.); (A.G.); (F.P.)
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy; (T.L.); (L.B.)
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22
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Cheng Z, Luo X, Zhu Z, Huang Y, Yan X. Furfural Produces Dose-Dependent Attenuating Effects on Ethanol-Induced Toxicity in the Liver. Front Pharmacol 2022; 13:906933. [PMID: 35754511 PMCID: PMC9214037 DOI: 10.3389/fphar.2022.906933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/12/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Alcohol-associated liver disease (ALD) increases the health burden worldwide, but effective drugs to prevent ALD are lacking. Furfural is a small molecule that can limit alcohol production in microorganisms and may have the capacity to attenuate ethanol-induced toxicity. Methods: Human HepG2 cells were incubated with ethanol and furfural, and cell viability, NAD+/NADH ratio, and mitochondrial function assays were performed. RNA sequencing (RNA-seq) data were used to annotate enriched pathways, and these findings were confirmed by reverse transcription-quantitative PCR (RT-qPCR) and Western blotting. C57BL/6J mice were fed a Lieber-DeCarli liquid diet. After 4 weeks, biochemical analysis of mouse serum and histological analysis of mouse livers were performed. Results: Different concentrations of furfural exerted different effects on mitochondria: low-dose furfural reduced reactive oxygen species (ROS) production, maintained mitochondrial transmembrane potential, and inhibited apoptosis pathway activation, while high-dose furfural led to the opposite effects. In mice, furfural mitigated transaminase increases and attenuated the lipid metabolism disorder that had been induced by ethanol. Conclusion: Low-dose furfural reduced ethanol-induced toxicity in the liver. Consuming food or beverages containing the appropriate level of furfural when drinking alcohol may be a convenient and useful way to prevent ALD.
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Affiliation(s)
- Zhuo Cheng
- The Department of Gastroenterology and Hepatology, Peking University Third Hospital, Beijing, China
| | - Xuanmei Luo
- National Center of Gerontology, Beijing Hospital, Beijing, China
| | - Zixin Zhu
- Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Yonghui Huang
- The Department of Gastroenterology and Hepatology, Peking University Third Hospital, Beijing, China
| | - Xiue Yan
- The Department of Gastroenterology and Hepatology, Peking University Third Hospital, Beijing, China
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23
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Han S, Yang Z, Zhang T, Ma J, Chandler K, Liangpunsakul S. Epidemiology of Alcohol-Associated Liver Disease. Clin Liver Dis 2021; 25:483-492. [PMID: 34229835 PMCID: PMC8996817 DOI: 10.1016/j.cld.2021.03.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Alcohol-associated liver disease (ALD) is a consequence of excessive alcohol use. It comprises a spectrum of histopathologic changes ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma. The public health impact of ALD is growing because of an increase in the prevalence and incidence of ALD in parallel with liver transplant and mortalities. There are multiple factors involved in the pathogenesis and progression of ALD. Reducing alcohol consumption is the cornerstone of ALD management. The efforts to reduce excessive alcohol use at the individual and population levels are urgently needed to prevent adverse outcomes from ALD.
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Affiliation(s)
- Sen Han
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA,Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, Beijing, China
| | - Zhihong Yang
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA
| | - Ting Zhang
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA
| | - Jing Ma
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA
| | - Kristina Chandler
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA
| | - Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202, USA,Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA,Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA,Corresponding author. Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN 46202.
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24
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Morgan MY, Sharma M, Atkinson SR. Genetic and Environmental Susceptibility to Alcoholic Hepatitis. Clin Liver Dis 2021; 25:517-535. [PMID: 34229837 DOI: 10.1016/j.cld.2021.04.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Constitutional, environmental, and genetic risk factors influence the development of alcohol-related cirrhosis. The amount of alcohol consumed and whether excessive drinking continues after the identification of pre-cirrhotic liver damage are key risk factors. Female sex, ethnicity, obesity, coffee consumption, cigarette smoking, and exposure to other causes of liver injury also influence the risk of disease development. More recently several genetic loci have been robustly associated with the risk for developing significant alcohol-related liver disease. It remains unclear whether additional risk factors are involved in the development of the clinical syndrome of alcoholic hepatitis, but the genetic evidence is suggestive.
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Affiliation(s)
- Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College, Rowland Hill Street, Hampstead, London NW3 2PF, UK.
| | - Moksh Sharma
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College, Rowland Hill Street, Hampstead, London NW3 2PF, UK
| | - Stephen R Atkinson
- Department of Metabolism, Digestion and Reproduction, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
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25
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Bernardo S, Crespo R, Saraiva S, Barata R, Gonçalves S, Nogueira P, Cortez-Pinto H, Machado MV. Outcomes of excessive alcohol drinkers without baseline evidence of chronic liver disease after 15 years follow-up: Heavy burden of cancer and liver disease mortality. PLoS One 2021; 16:e0252218. [PMID: 34033642 PMCID: PMC8148371 DOI: 10.1371/journal.pone.0252218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/12/2021] [Indexed: 12/20/2022] Open
Abstract
Background Most long-term heavy drinkers do not have clinically evident chronic liver disease (CLD). However, at any time-point, their risk of developing CLD remains unknown. We aimed to evaluate the long-term outcomes of a group of heavy drinkers, without evidence of CLD at baseline. Methods A cohort of 123 long-term heavy drinkers without CLD were prospectively recruited in 2002 and retrospectively followed until 2018. Results At baseline (2002), median alcohol consumption was 271±203g/day during 21.5±20 years, 65% being abstinent during the previous 1.75±5 months. Patients were followed for 14±3 years. During follow-up, 53% reported any alcohol intake. Alcohol consumption during follow-up associated weakly with either 1- or 6-months previous abstinence at baseline. Until 2018, progression to CLD occurred in 6%, associating with years of alcohol intake during follow-up (OR 1.15 [1.01–1.31]) and baseline alkaline-phosphatase (OR 1.05 [1.01–1.10]). During follow-up, being abstinent for at least 1 year positively associated with CLD-free survival. 27% died (55% of cancer–mostly oropharyngeal cancer, 27% of cardiovascular disease, and 9% of liver disease), with a mean age of 71 years [69–74] (10 years less than the expected in the Portuguese population). Achieving abstinence for at least 1 year positively associated with overall survival, while smoking, and hepatic steatosis at baseline associated negatively. Conclusion Long-term heavy drinkers seemed to have a decreased life expectancy compared with the overall Portuguese population. Cancer was the main cause of death. Our results suggest that progression to CLD depends mostly on continued alcohol intake. Alcohol abstinence, even if temporary, seems to decrease the risks of CLD and mortality.
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Affiliation(s)
- Sónia Bernardo
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
| | - Ricardo Crespo
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
| | - Sofia Saraiva
- Nephrology Department, Hospital de Curry Cabral, CHULC, Lisbon, Portugal
| | - Rui Barata
- Gastroenterology Department, Portuguese Oncology Institute, Lisbon, Portugal
| | - Sara Gonçalves
- Nephrology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
| | - Paulo Nogueira
- Biostatistics’ Department, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Helena Cortez-Pinto
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Mariana Verdelho Machado
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- * E-mail:
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26
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Wijarnpreecha K, Aby ES, Panjawatanan P, Lapumnuaypol K, Cheungpasitporn W, Lukens FJ, Harnois DM, Ungprasert P. Modest alcohol consumption and risk of advanced liver fibrosis in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Ann Gastroenterol 2021; 34:568-574. [PMID: 34276197 PMCID: PMC8276361 DOI: 10.20524/aog.2021.0612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 12/30/2020] [Indexed: 11/18/2022] Open
Abstract
Background Recent studies have suggested an association between modest alcohol consumption and a decreased risk of advanced liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) although the results are inconsistent. The current systematic review and meta-analysis was conducted to comprehensively investigate this possible association by identifying all the relevant studies and combining their results. Methods A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through February 2019 to identify all cross-sectional studies that compared the prevalence of advanced liver fibrosis among NAFLD patients who were modest alcohol drinkers to NAFLD patients who were non-drinkers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. Results A total of 6 studies with 8,936 participants fulfilled the eligibility criteria and were included in the meta-analysis. The risk of advanced liver fibrosis among patients with NAFLD who were modest alcohol drinkers was significantly lower compared to patients with NAFLD who were non-drinkers with a pooled odds ratio of 0.51 (95% confidence interval [CI] 0.35-0.75; I2 47%). The funnel plot was symmetric and was not suggestive of publication bias. Conclusion A significantly lower risk of advanced liver fibrosis was observed among NAFLD patients who were modest alcohol drinkers compared to non-drinkers in this meta-analysis.
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Affiliation(s)
- Karn Wijarnpreecha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA (Karn Wijarnpreecha, Denise M. Harnois)
| | - Elizabeth S Aby
- Department of Medicine, University of California at Los Angeles, CA, USA (Elizabeth S. Aby, Frank J. Lukens)
| | - Panadeekarn Panjawatanan
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (Panadeekarn Panjawatanan)
| | - Kamolyut Lapumnuaypol
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA (Kamolyut Lapumnuaypol)
| | - Wisit Cheungpasitporn
- Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, USA (Wisit Cheungpasitporn)
| | - Frank J Lukens
- Department of Medicine, University of California at Los Angeles, CA, USA (Elizabeth S. Aby, Frank J. Lukens)
| | - Denise M Harnois
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA (Karn Wijarnpreecha, Denise M. Harnois)
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand (Patompong Ungprasert)
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Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers. Am J Gastroenterol 2021; 116:106-115. [PMID: 32868629 DOI: 10.14309/ajg.0000000000000833] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 06/17/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.
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Yoon YH, Chen CM, Slater ME, Jung MK, White AM. Trends in Premature Deaths From Alcoholic Liver Disease in the U.S., 1999-2018. Am J Prev Med 2020; 59:469-480. [PMID: 32863077 PMCID: PMC7508789 DOI: 10.1016/j.amepre.2020.04.024] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/17/2020] [Accepted: 04/23/2020] [Indexed: 12/18/2022]
Abstract
INTRODUCTION So-called deaths of despair-those involving drug overdoses, alcohol-related liver disease, and suicide-have been rising in the U.S. among middle-aged white, non-Hispanic adults without a college degree. Premature deaths (ages 25-69) from alcoholic liver disease were examined specifically in this study from 1999 to 2018, by sex, race/Hispanic origin, and age group. METHODS Data were drawn from the 1999-2018 Multiple Cause of Death database and bridged-race estimates of the U.S. resident population, including 281,243 alcoholic liver disease deaths or an average of 8 deaths per 100,000 population. Analyses examined alcoholic liver disease death rates for sex differences among 3 age groups (25-49, 50-59, and 60-69 years), by race and Hispanic origin, from 1999 to 2018; age-adjusted and age-specific annual percentage changes (accounted for cohorts); years of potential life lost; and age of death for sociodemographic backgrounds, alcoholic liver disease clinical courses, and comortalities. RESULTS White non-Hispanics increasingly experienced greater alcoholic liver disease mortality than black non-Hispanics and Hispanics, confirming the racial and ethnic crossover observed in previous studies. Although men consistently had higher rates of mortality, male-to-female ratios decreased in the past 2 decades and were the lowest among ages 25-49 years and especially among ages 25-34 years. Although women generally had longer life expectancies, women died of alcoholic liver disease on average about 2-3 years earlier than men. CONCLUSIONS Prevention and intervention efforts are imperative to address the narrowing sex gap and widening racial disparities in alcoholic liver disease premature deaths.
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Affiliation(s)
| | | | | | - M Katherine Jung
- National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, Maryland
| | - Aaron M White
- National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, Maryland
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29
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Delacôte C, Bauvin P, Louvet A, Dautrecque F, Ntandja Wandji LC, Lassailly G, Voican C, Perlemuter G, Naveau S, Mathurin P, Deuffic-Burban S. A Model to Identify Heavy Drinkers at High Risk for Liver Disease Progression. Clin Gastroenterol Hepatol 2020; 18:2315-2323.e6. [PMID: 31931181 DOI: 10.1016/j.cgh.2019.12.041] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 12/08/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression. METHODS We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy. We collected data from both cohorts on patient history and disease stage at the time of hospitalization. For the development cohort, severity of the disease was scored by the METAVIR (due to the availability of liver histology reports); in the validation cohort only the presence of liver complications was assessed. We developed a model of ALD progression and occurrence of liver complications (hepatocellular carcinoma and/or liver decompensation) in association with exposure to alcohol, age at the onset of heavy drinking, amount of alcohol intake, sex and body mass index. The model was fitted to the development cohort and then evaluated in the validation cohort. We then tested the ability of the model to predict disease progression for any patient profile (baseline evaluation). Patients with a 5-y weighted risk of liver complications greater than 5% were considered at high risk for disease progression. RESULTS Model results are given for the following patient profiles: men and women, 40 y old, who started drinking at an age of 25 y, drank 150 g/day, and had a body mass index of 22 kg/m2 according to the disease severity at baseline evaluation. For men with baseline F0-F2 fibrosis, the model estimated the probabilities of normal liver, steatosis, or steatohepatitis at baseline to be 31.8%, 61.5% and 6.7%, respectively. The 5-y weighted risk of liver complications was 1.9%, ranging from 0.2% for men with normal liver at baseline evaluation to 10.3% for patients with steatohepatitis at baseline. For women with baseline F0-F2 fibrosis, probabilities of normal liver, steatosis, or steatohepatitis at baseline were 25.1%, 66.5% and 8.4%, respectively; the 5-y weighted risk of liver complications was 3.2%, ranging from 0.5% for women with normal liver at baseline to 14.7% for patients with steatohepatitis at baseline. Based on the model, men with F3-F4 fibrosis at baseline have a 24.5% 5-y weighted risk of complications (ranging from 20.2% to 34.5%) and women have a 30.1% 5-y weighted risk of complications (ranging from 24.7% to 41.0%). CONCLUSIONS We developed a Markov model that integrates data on level and duration of alcohol use to identify patients at high risk of liver disease progression. This model might be used to adapt patient care pathways.
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Affiliation(s)
- Claire Delacôte
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France
| | - Pierre Bauvin
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France
| | - Alexandre Louvet
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Flavien Dautrecque
- Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Line Carolle Ntandja Wandji
- Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Guillaume Lassailly
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Cosmin Voican
- Service d'hépato-gastro-entérologie et nutrition, Hôpital Antoine Béclère, Hôpitaux universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, Département Hospitalo-Universitaire Hepatinov, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Faculté de médecine Paris-Sud, Université Paris Sud-Université Paris Saclay, Le Kremlin-Bicêtre, France
| | - Gabriel Perlemuter
- Service d'hépato-gastro-entérologie et nutrition, Hôpital Antoine Béclère, Hôpitaux universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, Département Hospitalo-Universitaire Hepatinov, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Faculté de médecine Paris-Sud, Université Paris Sud-Université Paris Saclay, Le Kremlin-Bicêtre, France
| | - Sylvie Naveau
- Service d'hépato-gastro-entérologie et nutrition, Hôpital Antoine Béclère, Hôpitaux universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; INSERM U996, Département Hospitalo-Universitaire Hepatinov, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Faculté de médecine Paris-Sud, Université Paris Sud-Université Paris Saclay, Le Kremlin-Bicêtre, France
| | - Philippe Mathurin
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Service des maladies de l'appareil digestif et de la nutrition, Centre Hospitalier Universitaire de Lille, Lille, France.
| | - Sylvie Deuffic-Burban
- Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Université de Paris, IAME, INSERM, Paris, France.
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Marcellin F, Beo VD, Carrieri P. Alcohol Use Patterns and Liver Outcomes: Is There Really a Difference Between Drinking Beer and Drinking Wine? Clin Gastroenterol Hepatol 2020; 18:1650-1651. [PMID: 31887441 DOI: 10.1016/j.cgh.2019.12.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023]
Affiliation(s)
- Fabienne Marcellin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Vincent Di Beo
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d'Azur, Marseille, France
| | - Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d'Azur, Marseille, France
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Leitão J, Carvalhana S, Cochicho J, Silva AP, Velasco F, Medeiros I, Alves AC, Bourbon M, Oliveiros B, Rodrigues V, Sousa R, Sampaio F, Carvalho A, Cortez-Pinto H. Prevalence and risk factors of fatty liver in Portuguese adults. Eur J Clin Invest 2020; 50:e13235. [PMID: 32289180 DOI: 10.1111/eci.13235] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 03/17/2020] [Accepted: 03/29/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Prevalence of fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) depends mainly on obesity, diabetes and genetic factors. FL and NAFLD prevalence was evaluated in Portuguese adult population and correlated with several risk factors and related mortality data, within the same period. MATERIALS AND METHODS A cross-sectional, population-based multicenter study, voluntary and randomly selected in 834 Portuguese adults (18-79 years). Participants were evaluated after 12-hour fasting. Anthropometric data, past history including alcohol consumption, and associated diseases were registered. Blood samples were collected for biochemical testing. Dietary intake was evaluated using a semi-quantitative food frequency questionnaire. Presence of FL was evaluated using ultrasound, and NAFLD was diagnosed after exclusion of other causes for liver disease. RESULTS Adjusted prevalence of FL and NAFLD was 37.8% and 17.0%, respectively. FL individuals were older, more frequently males, with increased probability of having obesity, diabetes or harmful alcohol consumption (HAC). NAFLD individuals were also older, but had a similar sex distribution and an increased probability of obesity and diabetes. In both groups, no differences were found regarding dietary pattern or physical activity. During the same time period, nonalcoholic steatohepatitis (NASH) liver-related deaths in Portugal were 0.105/100 000, while alcohol-related liver disease mortality was 6.790/100 000. CONCLUSION The large spectrum of FL was present in more than one third of the population, although only less than half could be classified as NAFLD. Other significant risk factors, such as HAC, are probably implicated in FL, explaining the low NASH-related mortality compared with the high alcohol-related mortality during the same time period.
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Affiliation(s)
- Jorge Leitão
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Sofia Carvalhana
- Department of Gastroenterology, Centro Hospitalar e Universitário Lisboa Norte, Lisboa, Portugal
| | - Joana Cochicho
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Ana Paula Silva
- Department of Gastroenterology, Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - Francisco Velasco
- Department of Gastroenterology, Centro Hospitalar do Algarve, Hospital de Faro, Faro, Portugal
| | - Isabel Medeiros
- Department of Gastroenterology, Hospital Espírito Santo, Évora, Portugal
| | - Ana Catarina Alves
- Biosystems and Integrative Science Institute (BioISI), Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal
| | - Mafalda Bourbon
- Biosystems and Integrative Science Institute (BioISI), Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal
| | - Bárbara Oliveiros
- Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Vitor Rodrigues
- Instituto de Higiene e Medicina Social, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Rita Sousa
- Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - Filipa Sampaio
- Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.,Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
| | - Armando Carvalho
- Department of Internal Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Helena Cortez-Pinto
- Department of Gastroenterology, Centro Hospitalar e Universitário Lisboa Norte, Lisboa, Portugal.,Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
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Hauksson K, Arnardottir M, Agustsson AS, Magnusdottir BA, Baldursdottir MB, Lund SH, Kalaitzakis E, Björnsson ES. Increase in the incidence of alcoholic pancreatitis and alcoholic liver disease in Iceland: impact of per capita alcohol consumption. Scand J Gastroenterol 2020; 55:615-620. [PMID: 32289240 DOI: 10.1080/00365521.2020.1751874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: To analyze the incidence of acute alcoholic pancreatitis and of severe alcoholic liver disease (ALD) and its association with per capita alcohol consumption with identification of both alcoholic cirrhosis (AC) and severe alcoholic hepatitis (AH), in a population-based setting.Methods: A search was undertaken in diagnoses database for diagnostic codes in order to find patients hospitalized with incident acute alcoholic pancreatitis (AP) and alcoholic liver disease in Iceland in 2001-2015. Diagnoses were verified in all patients who were retrospectively reviewed. Those with ALD had either AC or AH. Alcohol sales during the study period were obtained from Statistics Iceland.Results: Overall, 273 patients with acute AP, mean age at diagnosis 50 (14) years, 74% males and 159 patients with ALD, mean age 57 (11) years, 73% males, were identified. Mean per capita alcohol consumption was 6.95 (0.4) liters and increased by 21% over the study period. The annual incidence of AP increased from 4.2 per 100.000 to 9.5 and ALD from 1.6 to 6.1 per 100.000. Trend analysis showed a significant annual increase of 7% (RR 1.07, 95%CI 1.04-1.10) for AP and an annual increase of 10.5% (RR 1.10, 95%CI 1.06-1.15) for ALD. The increase was only significant in males.Conclusions: Increase per capita alcohol consumption over a 15 year study period was associated with an increase in the incidence of severe alcoholic liver disease and alcohol-related acute pancreatitis in males but not in females.
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Affiliation(s)
- Kristjan Hauksson
- Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland
| | - Margret Arnardottir
- Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland
| | - Arnar S Agustsson
- Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland
| | | | | | - Sigrun H Lund
- Decode Genetics, Reykjavik, Iceland, Copenhagen, Denmark
| | - Evangelos Kalaitzakis
- Digestive Disease Center, Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark
| | - Einar S Björnsson
- Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland.,Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol 2020; 5:16. [PMID: 32258520 PMCID: PMC7063528 DOI: 10.21037/tgh.2019.09.08] [Citation(s) in RCA: 325] [Impact Index Per Article: 65.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 09/05/2019] [Indexed: 12/12/2022] Open
Abstract
Liver diseases are fast emerging as global health priorities. Fatty liver is described in the setting of non-alcoholic fatty liver disease (NAFLD) as well as alcoholic liver disease (ALD), the pathogenesis of excess fat being different in the two conditions while both are important components of the changing face of burden of liver diseases worldwide. They are intimately associated with a globalized economy and an increasingly homogenous socio- cultural order with a westernized lifestyle. The accompanying adoption of a progressively sedentary life, consumption of diet dense in calories facilitate development of NAFLD while a spiraling upward trend in alcohol use along with earlier age of drinking as well as increased amount of per capita alcohol consumption increases the prevalence of ALD globally. Adverse health outcomes in NAFLD as well as ALD are caused not only by progressive liver fibrosis that is the most significant factor for liver related and all-cause mortality in both but also by non-liver (cardiovascular, cancer, accidents, neurological) clinical outcomes that calls for a multidisciplinary and social approach to these conditions. We present here an outline of facets of epidemiology of both NAFLD as well as ALD along with its' public health implications. A broad-based integrated approach that incorporates social, behavioral as well as biological targets need to be undertaken at a health system level in a planned manner for these evolving liver health priorities that disproportionately challenges the low- and middle-income countries of Asia, South America and Africa.
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Affiliation(s)
- Souveek Mitra
- Indian Institute of Liver and Digestive Sciences Sitala (east), Jagadishpur, Sonarpur, Kolkata, India
| | - Arka De
- Department of Hepatology, Post Graduate Institute of Medical Education and Research Chandigarh, Chandigarh, India
| | - Abhijit Chowdhury
- Indian Institute of Liver and Digestive Sciences Sitala (east), Jagadishpur, Sonarpur, Kolkata, India
- Department of Hepatology School of Digestive and Liver Diseases Institute of Post Graduate Medical Education & Research Kolkata, India
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Avila MA, Dufour JF, Gerbes AL, Zoulim F, Bataller R, Burra P, Cortez-Pinto H, Gao B, Gilmore I, Mathurin P, Moreno C, Poznyak V, Schnabl B, Szabo G, Thiele M, Thursz MR. Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting. Gut 2020; 69:764-780. [PMID: 31879281 PMCID: PMC7236084 DOI: 10.1136/gutjnl-2019-319720] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 11/28/2019] [Accepted: 12/06/2019] [Indexed: 12/14/2022]
Abstract
Alcohol-related liver disease (ALD), which includes a range of disorders of different severity and is one of the most prevalent types of liver disease worldwide, has recently regained increased attention. Among other reasons, the realisation that any alcohol intake, regardless of type of beverage represents a health risk, and the new therapeutic strategies tested in recently published or undergoing clinical trials spur scientific interest in this area.In April 2019, Gut convened a round table panel of experts during the European Association for the Study of the Liver International Liver Congress in Vienna to discuss critical and up-to-date issues and clinical trial data regarding ALD, its epidemiology, diagnosis, management, pathomechanisms, possible future treatments and prevention. This paper summarises the discussion and its conclusions.
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Affiliation(s)
- Matias A Avila
- Hepatology, CIBERehd, IdiSNA, CIMA, University of Navarra, Pamplona, Spain
| | - Jean-François Dufour
- Hepatology, Department of Clinical Research and University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland
| | - Alexander L Gerbes
- Liver Centre Munich, Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Fabien Zoulim
- Hepatology Department, INSERM U1052, Hospices Civils de Lyon, Cancer Research Centerl of Lyon, University of Lyon, Lyon, France
| | - Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Helena Cortez-Pinto
- Departamento de Gastroenterologia, CHLN, Laboratorio de Nutriçao, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Ian Gilmore
- Liverpool Centre for Alcohol Research, University of Liverpool, Liverpool, UK
| | - Philippe Mathurin
- Service des Maladies de l'Appareil Digestif, INSERM U795, Hôpital Huriez, Lille, France
| | - Christophe Moreno
- Service de Gastroentérologie, Hépatopancréatologie et Oncologie Digestive, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Vladimir Poznyak
- Department of Mental Health and Substance Abuse, World Health Organization, Geneve, Switzerland
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Maja Thiele
- Department of Gastroenterology and Hepatology, and Department of Clinical Research, Odense University Hospital and University of Southern Denmark, Odense, Denmark
| | - Mark R Thursz
- Department of Metabolism, Faculty of Medicine, Imperial College, London, UK
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Jiang Y, Zhang T, Kusumanchi P, Han S, Yang Z, Liangpunsakul S. Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease. Biomedicines 2020; 8:50. [PMID: 32143280 PMCID: PMC7148483 DOI: 10.3390/biomedicines8030050] [Citation(s) in RCA: 117] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/20/2020] [Accepted: 02/29/2020] [Indexed: 12/12/2022] Open
Abstract
Once ingested, most of the alcohol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde. Two additional pathways of acetaldehyde generation are by microsomal ethanol oxidizing system (cytochrome P450 2E1) and catalase. Acetaldehyde can form adducts which can interfere with cellular function, leading to alcohol-induced liver injury. The variants of alcohol metabolizing genes encode enzymes with varied kinetic properties and result in the different rate of alcohol elimination and acetaldehyde generation. Allelic variants of these genes with higher enzymatic activity are believed to be able to modify susceptibility to alcohol-induced liver injury; however, the human studies on the association of these variants and alcohol-associated liver disease are inconclusive. In addition to acetaldehyde, the shift in the redox state during alcohol elimination may also link to other pathways resulting in activation of downstream signaling leading to liver injury.
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Affiliation(s)
- Yanchao Jiang
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (Y.J.); (T.Z.); (P.K.); (S.H.)
| | - Ting Zhang
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (Y.J.); (T.Z.); (P.K.); (S.H.)
| | - Praveen Kusumanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (Y.J.); (T.Z.); (P.K.); (S.H.)
| | - Sen Han
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (Y.J.); (T.Z.); (P.K.); (S.H.)
| | - Zhihong Yang
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (Y.J.); (T.Z.); (P.K.); (S.H.)
| | - Suthat Liangpunsakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (Y.J.); (T.Z.); (P.K.); (S.H.)
- Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA
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Sahlman P, Nissinen M, Puukka P, Jula A, Salomaa V, Männistö S, Lundqvist A, Valsta L, Perola M, Färkkilä M, Åberg F. Genetic and lifestyle risk factors for advanced liver disease among men and women. J Gastroenterol Hepatol 2020; 35:291-298. [PMID: 31260143 DOI: 10.1111/jgh.14770] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/13/2019] [Accepted: 06/18/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. METHODS Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41 260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. RESULTS A total of 355 liver events occurred during the mean 12.4-year follow-up (511 789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P = 0.0083 for men; HR 1.04, P = 0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P = 0.0006 for men; HR 1.58, P = 0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P = 0.024 for men; HR 2.7, P = 0.0109 for women), and weekly binge drinking (HR 2.4, P = 0.0024 for men; HR 7.4, P < 0.0001 for women) predicted development of severe liver disease. Among men, diabetes (HR 2.7, P = 0.0002), average alcohol consumption (HR for 10 g/day 1.1, P = 0.0022), non-married status (HR 1.9, P = 0.0397 for single; HR 2.4, P = 0.0002 for widowed/separated), and serum high-density lipoprotein (HR 2.2, P = 0.0022) and non-high-density lipoprotein cholesterol (HR 1.2, P = 0.0237) were additional risk factors. Alcohol intake increased the risk especially among persons with high WHR (P for interaction 0.009). CONCLUSIONS Age, patatin-like phospholipase-containing domain 3 haplotype, and WHR increase the risk for development of severe liver disease. We found strong synergism between alcohol and central obesity. Binge drinking is an additional risk factor.
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Affiliation(s)
- Perttu Sahlman
- Abdominal Center, Clinic of Gastroenterology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | - Markku Nissinen
- Abdominal Center, Clinic of Gastroenterology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | | | - Antti Jula
- National Institute for Health and Welfare, Helsinki, Finland
| | - Veikko Salomaa
- National Institute for Health and Welfare, Helsinki, Finland
| | - Satu Männistö
- National Institute for Health and Welfare, Helsinki, Finland
| | | | - Liisa Valsta
- National Institute for Health and Welfare, Helsinki, Finland
| | - Markus Perola
- National Institute for Health and Welfare, Helsinki, Finland
| | - Martti Färkkilä
- Abdominal Center, Clinic of Gastroenterology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
| | - Fredrik Åberg
- Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki University, Helsinki, Finland.,The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
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Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology 2020; 71:306-333. [PMID: 31314133 DOI: 10.1002/hep.30866] [Citation(s) in RCA: 549] [Impact Index Per Article: 109.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Affiliation(s)
- David W Crabb
- Indiana University School of Medicine, Indianapolis, IN
| | - Gene Y Im
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Gyongyi Szabo
- University of Massachusetts Medical School, Worcester, MA
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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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Majid B, Khan R, Junaid Z, Khurshid O, Rehman SH, Jaffri SN, Zaidi B, Zehra J, Batool S, Altaf S, Jatoi A, Safina F. Assessment of Knowledge About the Risk Factors of Chronic Liver Disease in Patients Admitted in Civil Hospital Karachi. Cureus 2019; 11:e5945. [PMID: 31799087 PMCID: PMC6860746 DOI: 10.7759/cureus.5945] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Background Chronic liver disease (CLD) encompasses a series of single or multifactorial insults to the liver, most common of which are hepatitis, alcohol abuse, and non-alcoholic liver disease. CLD represents a major public health problem worldwide as well as in Pakistan. Unfortunately, studies evaluating the awareness of its risk factors among people are quite scarce. The purpose of this study was to assess the knowledge about risk factors of CLD in patients admitted to Dr. Ruth K M Pfau, Civil Hospital Karachi (CHK). Methods This quantitative cross-sectional study was conducted at CHK, among 368 patients admitted to CHK, during the period from February 2018 to September 2018. Frequencies and percentages were evaluated for categorical variables using Statistical Package for Social Sciences (SPSS), version 22 (IBM Corp., Armonk, NY). Chi-square test was applied to determine if there was any significant association between the variables. A p-value of <0.05 was considered significant. Results A scoring scale was developed to assess the level of knowledge. We found that only 32% of our study population had good knowledge about the risk factors of CLD while majority of them (68%) had poor knowledge. Regarding individual risk factors, >60% patients were aware that obesity, high fat intake, prolonged use of drugs, use of alcohol and hepatitis B and C are risk factors of CLD, while most of them did not know diabetes to be a risk factor as well. 51.4% patients thought that hepatitis B and C could not be transmitted via sexual contact and from mother to her baby. There was a positive association between education level and awareness about the risk factors of CLD (p = 0.006). Conclusion Future interventions to increase public awareness about CLD should promptly be taken. The lack of knowledge about this disease is the main cause of its rapid increment and the reason why it is so prevalent in our part of the world especially Pakistan. More studies and nationwide awareness programs are needed to control its spread.
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Affiliation(s)
- Bushra Majid
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Rimsha Khan
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Zainab Junaid
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Onaiza Khurshid
- Obstetrics and Gynecology, Dow University of Health Sciences, Karachi, PAK
| | | | | | - Batool Zaidi
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Jabeen Zehra
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Sabika Batool
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Saman Altaf
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Aliya Jatoi
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Fatima Safina
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
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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: 220] [Impact Index Per Article: 36.7] [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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Zheng J, Tian X, Zhang W, Zheng P, Huang F, Ding G, Yang Z. Protective Effects of Fucoxanthin against Alcoholic Liver Injury by Activation of Nrf2-Mediated Antioxidant Defense and Inhibition of TLR4-Mediated Inflammation. Mar Drugs 2019; 17:E552. [PMID: 31569771 PMCID: PMC6836049 DOI: 10.3390/md17100552] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 09/22/2019] [Accepted: 09/27/2019] [Indexed: 12/14/2022] Open
Abstract
Fucoxanthin (Fx) is a natural extract from marine seaweed that has strong antioxidant activity and a variety of other bioactive effects. This study elucidated the protective mechanism of Fx on alcoholic liver injury. Administration of Fx was associated with lower pathological effects in liver tissue and lower serum marker concentrations for liver damage induced by alcohol. Fx also alleviated oxidative stress, and lowered the level of oxides and inflammation in liver tissue. Results indicate that Fx attenuated alcohol-induced oxidative lesions and inflammatory responses by activating the nuclear factor erythrocyte-2-related factor 2 (Nrf2)-mediated signaling pathway and down-regulating the expression of the toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway, respectively. Our findings suggest that Fx can be developed as a potential nutraceutical for preventing alcohol-induced liver injury in the future.
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Affiliation(s)
- Jiawen Zheng
- Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
| | - Xiaoxiao Tian
- Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
| | - Wen Zhang
- Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
| | - Pingan Zheng
- Zhejiang Hailisheng Group Co., Ltd., Zhoushan 316021, China.
| | - Fangfang Huang
- Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
| | - Guofang Ding
- Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
| | - Zuisu Yang
- Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China.
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Singh KR, Muktesh G, Gunjan D, Kochhar R, Singh V, Das A, Siddappa P, Singh K. Patterns of alcohol consumption and nutrition intake in patients with alcoholic liver disease and alcoholic pancreatitis in North Indian men. JGH OPEN 2019; 3:316-321. [PMID: 31406925 PMCID: PMC6684506 DOI: 10.1002/jgh3.12165] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 01/05/2019] [Accepted: 01/31/2019] [Indexed: 11/09/2022]
Abstract
Background and Aim Chronic alcoholism and nutrition play an important role in liver and pancreatic diseases. To compare drinking habits and nutritional data in patients with alcoholic liver disease (ALD) and alcoholic pancreatitis (ALP). Methods Clinical, anthropometric, dietary intake, laboratory, and imaging data were recorded in consecutive patients of ALD and ALP. Results In 150 patients of ALP (n = 76) and ALD (n = 74), the age of starting alcohol consumption (19.03 ± 3.78 vs 18.0 ± 2.59 years) and the mean amount of alcohol consumed per day (165.63 ± 87.99 vs 185.50 ± 113.54 g; P = 0.230) were similar. Patients with ALD consumed alcohol on a daily basis more frequently (90.5 vs 72.3%; P = 0.003) and had a longer duration of alcohol intake (21.6 + 0.2 vs 14.5 + 6.9 years; P < 0.0001) than patients in the ALP group. Binge drinking was more common in patients with ALP compared to patients with ALD (60.5 vs 20.3%); P < 0.0001). Patients with ALP had a lower body mass index (19.9 ± 3.49 vs 22.64 ± 4.88 kg/m2; P = 0.001) and more frequent decrease in mid arm circumference (57.9 vs 44.6%; P = 0.042) and triceps skin fold thickness (67.1 vs 52.7%; P = 0.072) compared to patients with ALD. Conclusion There was no difference in the age of starting alcohol consumption and mean amount of alcohol consumption per day between the groups. Patients with ALD were more likely to be daily drinkers with a longer duration of alcohol intake. However, binge drinking and malnourishment was more common in the ALP group.
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Affiliation(s)
- Karam R Singh
- Unit of Gastroenterology Regional Institute of Medical Sciences Imphal India
| | - Gaurav Muktesh
- Department of Gastroenterology Postgraduate Institute of Medical Education and Research Chandigarh India
| | - Deepak Gunjan
- Department of Gastroenterology All India Institute of Medical Sciences Delhi India
| | - Rakesh Kochhar
- Department of Gastroenterology Postgraduate Institute of Medical Education and Research Chandigarh India
| | - Virendra Singh
- Department of Hepatology Postgraduate Institute of Medical Education and Research Chandigarh India
| | - Ashim Das
- Department of Histopathology Postgraduate Institute of Medical Education and Research Chandigarh India
| | - Pradeep Siddappa
- Department of Gastroenterology Postgraduate Institute of Medical Education and Research Chandigarh India
| | - Kartar Singh
- Department of Gastroenterology Postgraduate Institute of Medical Education and Research Chandigarh India
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Li YM, Fan JG. Guidelines of prevention and treatment for alcoholic liver disease (2018, China). J Dig Dis 2019; 20:174-180. [PMID: 30450822 DOI: 10.1111/1751-2980.12687] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 11/12/2018] [Accepted: 11/15/2018] [Indexed: 12/11/2022]
Affiliation(s)
- You Ming Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jian Gao Fan
- Department of Gastroenterology, XinHua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Children's Digestion and Nutrition, Shanghai, China
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Simpson RF, Hermon C, Liu B, Green J, Reeves GK, Beral V, Floud S. Alcohol drinking patterns and liver cirrhosis risk: analysis of the prospective UK Million Women Study. Lancet Public Health 2019; 4:e41-e48. [PMID: 30472032 PMCID: PMC6323353 DOI: 10.1016/s2468-2667(18)30230-5] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/22/2018] [Accepted: 10/25/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Alcohol is a known cause of cirrhosis, but it is unclear if the associated risk varies by whether alcohol is drunk with meals, or by the frequency or type of alcohol consumed. Here we aim to investigate the associations between alcohol consumption with meals, daily frequency of consumption, and liver cirrhosis. METHODS The Million Women Study is a prospective study that includes one in every four UK women born between 1935 and 1950, recruited between 1996 and 2001. In 2001 (IQR 2000-03), the participants reported their alcohol intake, whether consumption was usually with meals, and number of days per week it was consumed. Cox regression analysis yielded adjusted relative risks (RRs) for incident cirrhosis, identified by follow-up through electronic linkage to routinely collected national hospital admission, and death databases. FINDINGS During a mean of 15 years (SD 3) of follow-up of 401 806 women with a mean age of 60 years (SD 5), without previous cirrhosis or hepatitis, and who reported drinking at least one alcoholic drink per week, 1560 had a hospital admission with cirrhosis (n=1518) or died from the disease (n=42). Cirrhosis incidence increased with amount of alcohol consumed (≥15 drinks [mean 220 g of alcohol] vs one to two drinks [mean 30 g of alcohol] per week; RR 3·43, 95% CI 2·87-4·10; p<0·0001). About half of the participants (203 564 of 401 806) reported usually drinking with meals and, after adjusting for amount consumed, cirrhosis incidence was lower for usually drinking with meals than not (RR 0·69, 0·62-0·77; p<0·0001; wine-only drinkers RR 0·69, 0·56-0·85; all other drinkers RR 0·72, 0·63-0·82). Among 175 618 women who consumed seven or more drinks per week, cirrhosis incidence was greater for daily consumption than non-daily consumption (adjusted RR 1·61, 1·40-1·85; p<0·0001). Daily consumption, together with not drinking with meals, was associated with more than a doubling of cirrhosis incidence (adjusted RR 2·47, 1·96-3·11; p<0·0001). INTERPRETATION In middle-aged women, cirrhosis incidence increases with total alcohol intake, even at moderate levels of consumption. For a given weekly intake of alcohol, this excess incidence of cirrhosis is higher if consumption is usually without meals, or with daily drinking. FUNDING UK Medical Research Council and Cancer Research UK.
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Affiliation(s)
- Rachel F Simpson
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK.
| | - Carol Hermon
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK
| | - Bette Liu
- School of Public Health and Community Medicine, University of New South Wales, Sydney 2052, Australia
| | - Jane Green
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK
| | - Gillian K Reeves
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK
| | - Valerie Beral
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK
| | - Sarah Floud
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, UK
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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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Meroni M, Longo M, Rametta R, Dongiovanni P. Genetic and Epigenetic Modifiers of Alcoholic Liver Disease. Int J Mol Sci 2018; 19:E3857. [PMID: 30513996 PMCID: PMC6320903 DOI: 10.3390/ijms19123857] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 10/31/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022] Open
Abstract
Alcoholic liver disease (ALD), a disorder caused by excessive alcohol consumption is a global health issue. More than two billion people consume alcohol in the world and about 75 million are classified as having alcohol disorders. ALD embraces a wide spectrum of hepatic lesions including steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). ALD is a complex disease where environmental, genetic, and epigenetic factors contribute to its pathogenesis and progression. The severity of alcohol-induced liver disease depends on the amount, method of usage and duration of alcohol consumption as well as on age, gender, presence of obesity, and genetic susceptibility. Genome-wide association studies and candidate gene studies have identified genetic modifiers of ALD that can be exploited as non-invasive biomarkers, but which do not completely explain the phenotypic variability. Indeed, ALD development and progression is also modulated by epigenetic factors. The premise of this review is to discuss the role of genetic variants and epigenetic modifications, with particular attention being paid to microRNAs, as pathogenic markers, risk predictors, and therapeutic targets in ALD.
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Affiliation(s)
- Marica Meroni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, Italy.
| | - Miriam Longo
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, Italy.
| | - Raffaela Rametta
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, Italy.
| | - Paola Dongiovanni
- General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, Italy.
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Coffee and wine consumption is associated with reduced mortality from alcoholic liver disease: follow-up of 219,279 Norwegian men and women aged 30–67 years. Ann Epidemiol 2018; 28:753-758. [DOI: 10.1016/j.annepidem.2018.08.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 08/08/2018] [Accepted: 08/21/2018] [Indexed: 12/22/2022]
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Thursz M, Gual A, Lackner C, Mathurin P, Moreno C, Spahr L, Sterneck M, Cortez-Pinto H. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69:154-181. [PMID: 29628280 DOI: 10.1016/j.jhep.2018.03.018] [Citation(s) in RCA: 573] [Impact Index Per Article: 81.9] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 12/12/2022]
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Boyle M, Masson S, Anstee QM. The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease. J Hepatol 2018; 68:251-267. [PMID: 29113910 DOI: 10.1016/j.jhep.2017.11.006] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 10/30/2017] [Accepted: 11/01/2017] [Indexed: 12/12/2022]
Abstract
Current medical practice artificially dichotomises a diagnosis of fatty liver disease into one of two common forms: alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Together, these account for the majority of chronic liver diseases worldwide. In recent years, there has been a dramatic increase in the prevalence of obesity and metabolic syndrome within the general population. These factors now coexist with alcohol consumption in a substantial proportion of the population. Each exposure sensitises the liver to the injurious effects of the other; an interaction that drives and potentially accelerates the genesis of liver disease. We review the epidemiological evidence and scientific literature that considers how alcohol consumption interacts with components of the metabolic syndrome to exert synergistic or supra-additive effects on the development and progression of liver disease, before discussing how these interactions may be addressed in clinical practice.
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Affiliation(s)
- Marie Boyle
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Steven Masson
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Quentin M Anstee
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Liver Unit, Newcastle Upon Tyne Hospitals NHS Trust, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
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Canha MI, Oliveiros B, Franco C, Figueiredo P. The lifestyle influence on alcoholic pancreatitis versus alcoholic liver disease: a case-control study. Scand J Gastroenterol 2017; 52:1278-1285. [PMID: 28830264 DOI: 10.1080/00365521.2017.1365167] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the association of lifestyle with the development of alcoholic liver disease (ALD) or alcoholic pancreatitis (AlcP). METHODS A case-control study was conducted on 80 patients attending a tertiary university hospital, subdivided into three groups: ALD (n = 34), AlcP (n = 21) and a control (CT) group (n = 25) of alcohol abusers without clinical evidence of hepatic or pancreatic disease. Participants were interviewed regarding alcohol consumption, tobacco use and diet. A physical examination was concomitantly performed and we had access to their complementary investigation. RESULTS We included 10 females and 70 males (mean age 57 ± 10 years). The pure amount of alcohol consumed by the ALD group was significantly higher than the AlcP group, regarding both daily (grams/day) and lifetime (kilograms) consumptions (p = .018 and p = .009, respectively); no statistically significant differences were seen with the CT group. We found no differences regarding the beverage type or drinking outside meals. Smoking was very common in every study group, with higher consumptions and a significantly higher prevalence of ever smokers in the AlcP group, in comparison with ALD and CT patients (p = .033 and p = .036, respectively). There were significant differences in the patients' eating habits before the onset of disease between groups (p < .001), with ALD subjects reporting a less abundant diet and AlcP a more abundant diet in the past; most of the controls had unchanged habits. CONCLUSION We found differences in lifestyle between ALD and AlcP, not considered sufficient to explain the subjects' susceptibility to one disease or the other.
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Affiliation(s)
- Maria Inês Canha
- a Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Bárbara Oliveiros
- b Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine , University of Coimbra (LBIM, FMUC) , Coimbra , Portugal.,c Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine , University of Coimbra (IBILI FMUC) , Coimbra , Portugal
| | - Célia Franco
- d Dual Disorders Unit, Psychiatric Service , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
| | - Pedro Figueiredo
- a Faculty of Medicine , University of Coimbra , Coimbra , Portugal.,e Department of Gastroenterology , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
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