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Poorolajal J, Shadi Y, Heshmati B. Interaction Between Hepatitis B, Hepatitis C and Alcohol in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. J Viral Hepat 2025; 32:e14042. [PMID: 39716779 DOI: 10.1111/jvh.14042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 11/26/2024] [Indexed: 12/25/2024]
Abstract
The objective of this report is to provide clarification on the interaction among hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol in the development of hepatocellular carcinoma (HCC). A systematic search was performed in PubMed, Web of Science and Scopus databases up to July 18, 2023. The inclusion criteria involved observational studies that examined the relationship between HBV, HCV, alcohol use and the development of HCC. To assess between-study heterogeneity, the I2 statistics were employed. Publication bias was evaluated using the Begg and Egger tests. The effect sizes were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) utilising a random-effects model. Among the initial pool of 31,021 studies identified, 28 studies involving 42,406 participants met the inclusion criteria. Through our meta-analysis, we found that the combined effect of HBV and alcohol was associated with an OR of 14.56 (95% CI: 9.80, 21.65). The combined impact of HCV and alcohol showed an OR of 42.44 (95% CI: 20.11, 89.56). Coinfection with both HBV and HCV was associated with an OR of 32.58 (95% CI: 20.57, 51.60). These results emphasising the importance of reducing alcohol consumption and implementing effective viral hepatitis prevention and treatment.
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Affiliation(s)
- Jalal Poorolajal
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
- Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Yahya Shadi
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Bahram Heshmati
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
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Roldan GA, Tricarico C, Brown RS. Alcohol Use Disorder and Alcohol-Associated Liver Disease: New Definitions, Screening, and Treatment. Gastroenterol Hepatol (N Y) 2024; 20:662-671. [PMID: 39886332 PMCID: PMC11775998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2025]
Abstract
Alcohol-associated liver disease (ALD) poses a significant global health burden and is a leading cause of liver-related morbidity and mortality. ALD encompasses a spectrum of disease states ranging from asymptomatic steatosis to acute hepatitis and cirrhosis. Alcohol use disorder (AUD) significantly increases the risk of developing ALD, and insight into AUD can provide a more complete understanding of ALD and the patients affected by these interrelated diseases. Accurate and timely identification of AUD, even in primary care, through validated screening tools combined with blood tests and imaging techniques facilitates early detection of ALD. Although liver transplantation (LT) remains the most effective treatment for end-stage ALD, patient outcomes post-LT have evolved because of shifting perspectives on ALD transplant eligibility, comprehensive pre-LT evaluations, and advancements in post-LT ALD detection. Nonetheless, addressing disparities in LT practices for ALD is paramount for ensuring equitable access to this life-saving intervention. This article offers an updated synopsis of ALD definitions, screening methodologies, and contemporary management approaches, particularly in the context of LT.
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Affiliation(s)
- Giovanni A. Roldan
- Department of Gastroenterology and Hepatology, Columbia University Irving Medical Center, Columbia University, New York, New York
- Department of Gastroenterology and Hepatology, University of Minnesota, Minneapolis, Minnesota
| | | | - Robert S. Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York
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Al-Sheddi ES, Farshori NN, Al-Oqail MM, Alblwi F, Ahmad J, Al-Khedhairy AA, Siddiqui MA. Hepatoprotective effect of date fruit extract against ethanol-induced apoptosis in human hepatoma (HepG2) cells. Tissue Cell 2024; 90:102519. [PMID: 39141932 DOI: 10.1016/j.tice.2024.102519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 07/23/2024] [Accepted: 08/08/2024] [Indexed: 08/16/2024]
Abstract
Ethanol is a well-known hepatotoxic agent and date fruits have been associated with their biological actions. In current study, we have investigated the hepatoprotective potential of DFE on ethanol-induced cellular damages in human hepatoma (HepG2) cells. The hepatoprotective potential was assessed by exposing the HepG2 cells to non-toxic concentrations (15, 30, and 60 μg/mL) of DFE for 24 h; then toxic concentration (500 μM) of ethanol. Our results demonstrated that pretreatment with DFE significantly prohibited ethanol-induced hepatotoxicity in HepG2 cells. We observed that DFE treatment increased cell viability, reduced LDH leakage, restored cellular morphology, and inhibited caspase-3 enzyme activity in a dose dependent way, induced by ethanol. Further DFE was also effective in restoring the LPO, GSH, and catalase levels towards normal altered by ethanol. Our results also revealed that ethanol-induced ROS generation was significantly inhibited by DFE. The ethanol-induced mRNA expression of apoptotic related genes (p53, caspase-3, caspase-7, Bax, and Bcl-2) were also normalized by pretreatment with DFE. The findings from this study indicated that DFE can significantly protect HepG2 cells against ethanol-induced hepatotoxicity. Our study also provides scientific validation for the traditional use of DFE, aiming to understand its hepatoprotective potential. Altogether, to the best of our knowledge, this is the first study demonstrated that ethanol-induced hepatotoxicity can be prohibited by the DFE. Thus, DFE has a potential application in nutraceuticals as a therapeutic agent to prevent liver diseases.
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Affiliation(s)
- Ebtesam S Al-Sheddi
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
| | - Nida N Farshori
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
| | - Mai M Al-Oqail
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
| | - Fdyah Alblwi
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
| | - Javed Ahmad
- Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Abdulaziz A Al-Khedhairy
- Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Maqsood A Siddiqui
- Chair for DNA Research, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
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Wester A, Shang Y, Toresson Grip E, Matthews AA, Hagström H. Glucagon-like peptide-1 receptor agonists and risk of major adverse liver outcomes in patients with chronic liver disease and type 2 diabetes. Gut 2024; 73:835-843. [PMID: 38253482 PMCID: PMC11041618 DOI: 10.1136/gutjnl-2023-330962] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 01/13/2024] [Indexed: 01/24/2024]
Abstract
OBJECTIVE Phase II trials suggest glucagon-like peptide-1 receptor (GLP1) agonists resolve metabolic dysfunction-associated steatohepatitis but do not affect fibrosis regression. We aimed to determine the long-term causal effect of GLP1 agonists on the risk of major adverse liver outcomes (MALO) in patients with any chronic liver disease and type 2 diabetes. DESIGN We used observational data from Swedish healthcare registers 2010-2020 to emulate a target trial of GLP1 agonists in eligible patients with chronic liver disease and type 2 diabetes. We used an inverse-probability weighted marginal structural model to compare parametric estimates of 10-year MALO risk (decompensated cirrhosis, hepatocellular carcinoma, liver transplantation or MALO-related death) in initiators of GLP1 agonists with non-initiators. We randomly sampled 5% of the non-initiators to increase computational efficiency. RESULTS GLP1 agonist initiators had a 10-year risk of MALO at 13.3% (42/1026) vs 14.6% in non-initiators (1079/15 633) in intention-to-treat analysis (risk ratio (RR)=0.91, 95% CI=0.50 to 1.32). The corresponding 10-year per-protocol risk estimates were 7.4% (22/1026) and 14.4% (1079/15 633), respectively (RR=0.51, 95% CI=0.14 to 0.88). The per-protocol risk estimates at 6 years were 5.4% (21/1026) vs 9.0% (933/15 633) (RR=0.60, 95% CI=0.29 to 0.90) and at 8 years 7.2% (22/1026) vs 11.7% (1036/15 633) (RR=0.61, 95% CI=0.21 to 1.01). CONCLUSION In patients with chronic liver disease and type 2 diabetes who adhered to therapy over time, GLP1 agonists may result in lower risk of MALO. This suggests that GLP1 agonists are promising agents to reduce risk of chronic liver disease progression in patients with concurrent type 2 diabetes, although this needs to be corroborated in randomised trials.
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Affiliation(s)
- Axel Wester
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Ying Shang
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Emilie Toresson Grip
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- Quantify Research, Stockholm, Sweden
| | - Anthony A Matthews
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden
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Mekuria A, Xia L, Ahmed TA, Bishaw S, Teklemariam Z, Nedi T, Abula T, Engidawork E, Gong YY. Contribution of Aflatoxin B 1 Exposure to Liver Cirrhosis in Eastern Ethiopia: A Case-Control Study. Int J Gen Med 2023; 16:3543-3553. [PMID: 37605782 PMCID: PMC10440104 DOI: 10.2147/ijgm.s425992] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/14/2023] [Indexed: 08/23/2023] Open
Abstract
Background Liver cirrhosis is a global health problem due to a large number of disability-associated life years and mortality. However, evidence is scarce on its causes in Eastern-Ethiopia, a place where there is a high prevalence of liver cirrhosis of unknown etiology. This study attempted to identify the risk factors related to liver cirrhosis in the area. Methods A case-control study was conducted at a tertiary care hospital from January 2020 to July 2021. Following diagnoses using an ultrasound-based cirrhosis scale, a total of 127 cases were identified and compared with 253 control patients. A structured questionnaire and data abstraction form were used to collect demographic, lifestyle, and clinical information. A blood sample was also taken from each participant for clinical chemistry, hepatitis B virus (HBV), and hepatitis C virus tests as well as for an aflatoxin B1 (AFB1) albumin adduct (AF-alb) assay. Binary logistic regression analysis was used to determine predictors of liver cirrhosis. Results AF-alb levels were detected in 75% of the cases and 64% of the controls, with a median (IQR) level of 11 pg/mg (5.5-25) and 7.0 pg/mg (4.3-20.5), respectively (p<0.05). Moreover, the number of subjects with high AF-alb levels (≥8.6 pg/mg) was greater in cases (45%, p<0.05)) than controls (28%). Age ≥55 years (adjusted odds ratio (AOR)=0.4; 95% CI: 0.2, 0.8), being a farmer (AOR= 3.0; 95% CI: 1.5, 6.0), family history of liver disease (AOR= 2.9; 95% CI: 1.1, 7.9), HBV seropositivity (AOR=4.0; 95% CI: 1.9, 8.8), and exposure to high levels of AF-alb (AOR=2.0; 95% CI: 1.1, 3.7) were significantly associated with liver cirrhosis. Conclusion This study found a strong link between AFB1 exposure and liver cirrhosis. Mitigation of aflatoxin exposure and a better understanding of additional environmental risk factors like pesticides may be necessary to reduce the disease burden in Ethiopia.
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Affiliation(s)
- Abraham Mekuria
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Lei Xia
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Tekabe Abdosh Ahmed
- Department of Internal Medicine, School of Medicine, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Solomon Bishaw
- Department of Radiology, School of Medicine, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Zelalem Teklemariam
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Teshome Nedi
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Tefera Abula
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Ephrem Engidawork
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Yun Yun Gong
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
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Fuster D, Llorente C, Garcia-Calvo X, Bolao F, Zuluaga P, Hernández-Rubio A, Casado-Carbajo J, Leis A, Muga R. Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:1582-1589. [PMID: 37364901 PMCID: PMC10984271 DOI: 10.1111/acer.15140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 05/30/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. METHODS We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. RESULTS We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). CONCLUSIONS In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.
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Affiliation(s)
- Daniel Fuster
- Department of Internal Medicine. Addiction Unit. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), Spain
| | - Cristina Llorente
- Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Xavier Garcia-Calvo
- Department of Internal Medicine. Addiction Unit. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), Spain
| | - Ferran Bolao
- Department of Internal Medicine. Hospital Universitari de Bellvitge. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat (Barcelona), Spain
| | - Paola Zuluaga
- Department of Internal Medicine. Addiction Unit. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), Spain
| | - Anna Hernández-Rubio
- Department of Internal Medicine. Addiction Unit. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), Spain
| | - Julia Casado-Carbajo
- Department of Internal Medicine. Addiction Unit. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), Spain
| | - Alba Leis
- Department of Biochemistry. Hospital Universitari Germans Trias i Pujol de Badalona. Badalona (Barcelona), Spain
| | - Robert Muga
- Department of Internal Medicine. Addiction Unit. Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona (Barcelona), Spain
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Buyco DG, Dempsey JL, Scorletti E, Jeon S, Lin C, Harkin J, Bayen S, Furth EE, Martin J, Delima M, Hooks R, Sostre-Colón J, Gharib SA, Titchenell PM, Carr RM. Concomitant western diet and chronic-binge alcohol dysregulate hepatic metabolism. PLoS One 2023; 18:e0281954. [PMID: 37134024 PMCID: PMC10155975 DOI: 10.1371/journal.pone.0281954] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 02/03/2023] [Indexed: 05/04/2023] Open
Abstract
BACKGROUND AND AIMS There is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) with regards to risk factors and disease progression. However, the mechanism by which fatty liver disease arises from concomitant obesity and overconsumption of alcohol (syndrome of metabolic and alcohol-associated fatty liver disease; SMAFLD), is not fully understood. METHODS Male C57BL6/J mice were fed chow diet (Chow) or high-fructose, high-fat, high-cholesterol diet (FFC) for 4 weeks, then administered either saline or ethanol (EtOH, 5% in drinking water) for another 12 weeks. The EtOH treatment also consisted of a weekly 2.5 g EtOH/kg body weight gavage. Markers for lipid regulation, oxidative stress, inflammation, and fibrosis were measured by RT-qPCR, RNA-seq, Western blot, and metabolomics. RESULTS Combined FFC-EtOH induced more body weight gain, glucose intolerance, steatosis, and hepatomegaly compared to Chow, EtOH, or FFC. Glucose intolerance by FFC-EtOH was associated with decreased hepatic protein kinase B (AKT) protein expression and increased gluconeogenic gene expression. FFC-EtOH increased hepatic triglyceride and ceramide levels, plasma leptin levels, hepatic Perilipin 2 protein expression, and decreased lipolytic gene expression. FFC and FFC-EtOH also increased AMP-activated protein kinase (AMPK) activation. Finally, FFC-EtOH enriched the hepatic transcriptome for genes involved in immune response and lipid metabolism. CONCLUSIONS In our model of early SMAFLD, we observed that the combination of an obesogenic diet and alcohol caused more weight gain, promoted glucose intolerance, and contributed to steatosis by dysregulating leptin/AMPK signaling. Our model demonstrates that the combination of an obesogenic diet with a chronic-binge pattern alcohol intake is worse than either insult alone.
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Affiliation(s)
- Delfin Gerard Buyco
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Joseph L. Dempsey
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Eleonora Scorletti
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Sookyoung Jeon
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon-do, Republic of Korea
| | - Chelsea Lin
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Julia Harkin
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Susovon Bayen
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Emma E. Furth
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Jasmin Martin
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Monique Delima
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Royce Hooks
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Jaimarie Sostre-Colón
- Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Sina A. Gharib
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States of America
- Center for Lung Biology, University of Washington, Seattle, Washington, United States of America
| | - Paul M. Titchenell
- Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
| | - Rotonya M. Carr
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Division of Gastroenterology, Department of Medicine, School of Medicine, University of Washington, Seattle, Washington, United States of America
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Hagström H, Yan J, Talbäck M, Andreasson A, Walldius G, Bottai M, Hammar N. Improved prediction of 10-year risk of severe liver disease in the general population using commonly available biomarkers. Aliment Pharmacol Ther 2023; 57:418-425. [PMID: 36566508 PMCID: PMC10107149 DOI: 10.1111/apt.17374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/03/2022] [Accepted: 12/11/2022] [Indexed: 12/26/2022]
Abstract
BACKGROUND Estimating the risk for cirrhosis in the general population is complex. Existing prediction tools are in general unsatisfactory. AIMS To explore if using commonly available biomarkers can improve the commonly used FIB-4 score in the identification of subgroups at risk of cirrhosis. METHODS We used laboratory and clinical data on 126,925 individuals aged 35-79 years in Stockholm, Sweden, undergoing health examinations from 1985 to 1996. We used Swedish nationwide registries to ascertain 10-year cumulative incidence of severe liver disease, a composite of diagnoses corresponding to cirrhosis and its complications. We considered combinations of biomarkers associated with severe liver disease to identify subgroups with different risk profiles. RESULTS During an average follow-up of 9.3 years, we ascertained 630 incident cases of severe liver disease (0.5%). Age, the FIB-4 score, diabetes or impaired glucose and gamma-glutamyl transferase (gGT) were the most relevant characteristics for classifying risk profiles. Using these factors, we identified 24 groups with a cumulative incidence of severe liver disease at 10 years ranging from 0.2% (age 35-65, low FIB-4, no diabetes or impaired glucose and normal gGT) to 32.1% (age 35-65, high FIB-4, diabetes or impaired glucose and high gGT). CONCLUSIONS Identification of subjects at increased risk of severe liver disease in the general population using the FIB-4 score can be substantially improved by adding age and specific biomarkers commonly available in the primary care setting. These parameters should be considered for inclusion in the development of future risk prediction models.
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Affiliation(s)
- Hannes Hagström
- Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Jacinth Yan
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Mats Talbäck
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Anna Andreasson
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Department of Psychology, Stress Research Institute, Stockholm University, Stockholm, Sweden
| | - Göran Walldius
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Matteo Bottai
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Niklas Hammar
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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Karabegović I, Abozaid Y, Maas SCE, Labrecque J, Bos D, De Knegt RJ, Ikram MA, Voortman T, Ghanbari M. Plasma MicroRNA Signature of Alcohol Consumption: The Rotterdam Study. J Nutr 2022; 152:2677-2688. [PMID: 36130258 PMCID: PMC9839997 DOI: 10.1093/jn/nxac216] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/16/2022] [Accepted: 09/13/2022] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) represent a class of noncoding RNAs that regulate gene expression and are implicated in the pathogenesis of different diseases. Alcohol consumption might affect the expression of miRNAs, which in turn could play a role in risk of diseases. OBJECTIVES We investigated whether plasma concentrations of miRNAs are altered by alcohol consumption. Given the existing evidence showing the link between alcohol and liver diseases, we further explored the extent to which these associations are mediated by miRNAs. METHODS Profiling of plasma miRNAs was conducted using the HTG EdgeSeq miRNA Whole Transcriptome Assay in 1933 participants of the Rotterdam Study. Linear regression was implemented to explore the link between alcohol consumption (glasses/d) and miRNA concentrations, adjusted for age, sex, cohort, BMI, and smoking. Sensitivity analysis for alcohol categories (nondrinkers, light drinkers, and heavy drinkers) was performed, where light drinkers corresponded to 0-2 glasses/d in men and 0-1 glasses/d in women, and heavy drinkers to >2 glasses/d in men and >1 glass/d in women. Moreover, we utilized the alcohol-associated miRNAs to explore their potential mediatory role between alcohol consumption and liver-related traits. Finally, we retrieved putative target genes of identified miRNAs to gain an understanding of the molecular pathways concerning alcohol consumption. RESULTS Plasma concentrations of miR-193b-3p, miR-122-5p, miR-3937, and miR-4507 were significantly associated with alcohol consumption surpassing the Bonferroni-corrected P < 8.46 × 10-5. The top significant association was observed for miR-193b-3p (β = 0.087, P = 2.90 × 10-5). Furthermore, a potential mediatory role of miR-3937 and miR-122-5p was observed between alcohol consumption and liver traits. Pathway analysis of putative target genes revealed involvement in biological regulation and cellular processes. CONCLUSIONS This study indicates that alcohol consumption is associated with plasma concentrations of 4 miRNAs. We outline a potential mediatory role of 2 alcohol-associated miRNAs (miR-3937 and miR-122-5p), laying the groundwork for further exploration of miRNAs as potential mediators between lifestyle factors and disease development.
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Affiliation(s)
- Irma Karabegović
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Yasir Abozaid
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Silvana C E Maas
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands,Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Jeremy Labrecque
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Daniel Bos
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands,Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Robert J De Knegt
- Department of Gastroenterology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Trudy Voortman
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands,Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
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10
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Zoller H, Schaefer B, Vanclooster A, Griffiths B, Bardou-Jacquet E, Corradini E, Porto G, Ryan J, Cornberg M. EASL Clinical Practice Guidelines on haemochromatosis. J Hepatol 2022; 77:479-502. [PMID: 35662478 DOI: 10.1016/j.jhep.2022.03.033] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 12/15/2022]
Abstract
Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 μg/L in females and TSAT >50% and ferritin >300 μg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 μg/L during the induction phase and <100 μg/L during the maintenance phase.
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11
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Abassa KK, Wu XY, Xiao XP, Zhou HX, Guo YW, Wu B. Effect of alcohol on clinical complications of hepatitis virus-induced liver cirrhosis: a consecutive ten-year study. BMC Gastroenterol 2022; 22:130. [PMID: 35305565 PMCID: PMC8934474 DOI: 10.1186/s12876-022-02198-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 03/04/2022] [Indexed: 12/12/2022] Open
Abstract
Background and aims Although coexisting alcohol-induced liver disease and hepatitis B or C virus-induced liver cirrhosis (ALD + HBV or ALD + HCV) has been the center of recent hepatology researches, numerous controversies still persist. This study aimed to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis. Methods Patients diagnosed with liver cirrhosis (n = 22,287) from January 2010 to December 2019 were enrolled, and divided into five groups according to the etiology: alcohol-induced liver disease (ALD, 1652 cases), hepatitis B virus (HBV, 18,079 cases), hepatitis C virus (HCV, 682 cases), ALD + HBV (1594 cases) and ALD + HCV (280 cases). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups. Results The proportions of patients with Child Pugh grade C (28.0% vs 18.8%, P < 0.001) or MELD greater than 18 (24.1% vs 18.5%, P < 0.001) in the ALD + HBV group exceeded significantly those in the HBV group. Multivariate logistic regression revealed that the risk of hepatocellular carcinoma (HCC) and that of esophageal gastric variceal bleeding (EGVB) in the ALD + HBV group was respectively 2.01-fold and 1.74-fold that in the HBV group (HCC: OR = 2.01, 95% CI [1.58–2.55]; EGVB: OR = 1.74, 95% CI [1.30–2.33]) after adjusting for potential confounders. Furthermore, a linear-by-linear analysis test showed a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence. Moreover, patients with both antiviral treatment and alcohol abstinence had the lowest risk of HCC and EGVB (HCC: OR = 0.10, 95% CI [0.05–0.20], P < 0.001; EGVB: OR = 0.17, 95% CI [0.06–0.45], P < 0.001) compared to those without any treatment, those with abstinence alone and those with antiviral therapy alone. Similar pattern was noticed while comparing the ALD + HCV group to the HCV group. Conclusion Heavy alcohol use increased the severity of liver function impairment and the prevalence of HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long-term alcohol abstinence coupled with antiviral treatment effectively decreased the risk of HCC and EGVB in these populations. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02198-w.
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12
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Mao J, Zhan H, Meng F, Wang G, Huang D, Liao Z, Chen M. Costunolide protects against alcohol-induced liver injury by regulating gut microbiota, oxidative stress and attenuating inflammation in vivo and in vitro. Phytother Res 2022; 36:1268-1283. [PMID: 35084790 DOI: 10.1002/ptr.7383] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 12/14/2021] [Accepted: 12/29/2021] [Indexed: 12/17/2022]
Abstract
Costunolide (cos) derived from the roots of Dolomiaea souliei (Franch.), which belongs to the Dolomiaea genus in the family Compositae, exert the anti-inebriation effect mainly by inhibiting the absorption of alcohol in the gastrointestinal tract. However, the protective effect of cos against alcohol-induced liver injury (ALI) remains obscure. The present study was aimed to evaluate the hepatoprotective effects of cos (silymarin was used as positive control) against ALI and its potential mechanisms. MTT was used to examine the effect of cos on the cell viability of L-02 cells. Plasma was separated from blood that used to test the levels of TNF-α, IL-6 and IL-12, and LPS while serum separated from blood which used to detect the level of ALT and AST. Liver tissues were obtained for histopathological examination and western blot analysis. Fresh mice feces samples were collected for the detection of bacterial composition. Cos exhibited protective effect against alcoholic-induced liver injury by regulating gut microbiota capacities (higher relative abundance of Firmicutes and Actinobacteria while lower in Bacteroidetes and Proteobacteria), adjusting oxidative stress (reduced the activities of MDA and ROS while promoted SOD, GSH and GSH-PX in L-02 cells) and attenuating inflammation (decreased the levels of ALT, AST, LPS, IL-6, IL-12 and TNF-α) via LPS-TLR4-NF-κB p65 signaling pathway, which might be an active therapeutic agent for treatment of ALI.
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Affiliation(s)
- Jingxin Mao
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Honghong Zhan
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Fancheng Meng
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Guowei Wang
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Dan Huang
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
| | - Zhihua Liao
- School of Life Sciences, Southwest University, Chongqing, China
| | - Min Chen
- College of Pharmaceutical Sciences, Southwest University, Chongqing, China
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13
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John BV, Dahman B, Deng Y, Khakoo NS, Taddei TH, Kaplan DE, Levy C. Rates of decompensation, hepatocellular carcinoma and mortality in AMA-negative primary biliary cholangitis cirrhosis. Liver Int 2022; 42:384-393. [PMID: 34614294 PMCID: PMC8810619 DOI: 10.1111/liv.15079] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 09/21/2021] [Accepted: 09/30/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND The natural history of patients with anti-mitochondrial antibody (AMA)-negative Primary Biliary Cholangitis (PBC) cirrhosis has not been well defined, with prior studies showing discordant results. Furthermore, most studies of AMA-negative PBC have limited numbers of patients with cirrhosis and liver-related outcomes. METHODS We investigated the association of AMA-negative PBC and the development of death, liver-related death, decompensation and hepatocellular carcinoma (HCC), in a large cohort of predominantly male patients with PBC cirrhosis assembled from the Veterans Health Administration. RESULTS In a cohort of 521 patients with PBC cirrhosis (65 AMA-negative) with a total follow-up of 2504.3 person-years (PY) from cirrhosis diagnosis, patients with AMA-negative PBC were younger and more likely to be black but had similar rates of UDCA response. AMA-negative PBC cirrhosis was associated with similar unadjusted rates of liver-related death (4.6 vs 5.9 per 100 PY, P = .44), overall death (7.7 vs 9.6 per 100 PY, P = .31), decompensation (7.3 vs 5.1 per 100 PY, P = .12) and HCC (0.6 vs 1.0 per 100 PY, P = .63) to AMA-positive PBC. After adjusting for confounders, AMA-negative PBC cirrhosis was associated with similar rates of liver-related death (sub-Hazard Ratio [sHR] 1.27, 95% CI 0.71-2.28, P = .42, death [sHR] 1.24, 95% CI 0.81-1.90, P = .32), decompensation (sHR 1.05, 95% CI 0.56-1.98, P = .87) and HCC (sHR 0.48, 95% CI 0.11-2.10, P = .33) to AMA-positive patients. CONCLUSION In a cohort of predominantly male patients, AMA-negative PBC cirrhosis was associated with similar rates of overall or liver-related death, HCC or decompensation compared with AMA-positive disease.
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Affiliation(s)
- Binu V John
- Division of Hepatology, Bruce W Carter VA Medical Center, Miami, Florida, USA
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Bassam Dahman
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Yangyang Deng
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Nidah S Khakoo
- Department of Medicine, Jackson Memorial Hospital, Miami, Florida, USA
| | - Tamar H Taddei
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- VA Connecticut Healthcare System, West Haven, Connecticut, USA
| | - David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Division of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
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14
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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15
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Xu HQ, Wang CG, Zhou Q, Gao YH. Effects of alcohol consumption on viral hepatitis B and C. World J Clin Cases 2021; 9:10052-10063. [PMID: 34904075 PMCID: PMC8638036 DOI: 10.12998/wjcc.v9.i33.10052] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/15/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.
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Affiliation(s)
- Hong-Qin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Chun-Guang Wang
- Department of Surgery, The Second Hospital of Jilin University, Jilin University, Changchun 130041, Jilin Province, China
| | - Qiang Zhou
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Yan-Hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
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16
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Preciado-Puga MC, Ruiz-Noa Y, Garcia-Ramirez JR, Jordan-Perez B, Garnelo-Cabañas S, Lazo de la Vega-Monroy ML, Gutierrez-Aguirre KI, Ibarra-Reynoso LR. Non-invasive diagnosis of non-alcoholic fatty liver disease using an algorithm combining clinical indexes and ultrasonographic measures. Ann Hepatol 2021; 21:100264. [PMID: 33031969 DOI: 10.1016/j.aohep.2020.09.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/20/2020] [Accepted: 09/20/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVE Non-Alcoholic Fatty Liver Disease (NAFLD) is a metabolic liver disease related to insulin resistance, which requires invasive methods for diagnosis. The aim of this study was to analyze whether the use of an algorithm involving both clinical indices and hepatic ultrasound measurements improves the accuracy for the non-invasive diagnosis of NAFLD. PATIENTS AND METHODS Cross-sectional study with patients undergoing elective cholecystectomy. We collected anthropometric, metabolic, liver biopsy, and liver ultrasonography data. We calculated unpaired t-test and Pearson's coefficient, and areas under the receiver-operating characteristic curves (AUROC) for the Fatty Liver Index (FLI), Lipid Accumulation Product (LAP) indexes, right liver index diameter, and for predictive models constructed with discriminant analysis. RESULTS One hundred patients in groups with and without NAFLD. FLI, LAP, right and caudate liver lobe diameters, and congestion index were higher in NAFLD group (p = 0.011, p = 0.011, p = 0.001, p = 0.027, p = 0.009). The right liver lobe diameter had the highest AUROC. Predictive models that combined sensitivity and specificity for the clinical indexes and liver ultrasound had an AUROC over 0.7. CONCLUSION The ultrasonography measure of right liver lobe diameter by itself can reliably identify patients with NAFLD with a good sensitivity and specificity, however, this can be improved by adding the LAP mathematical index in our population.
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Affiliation(s)
- Monica C Preciado-Puga
- Department of Medicine and Nutrition, Health Sciences Division, University of Guanajuato, Leon, Campus, Boulevard Puente del Milenio 1001, Colonia Predio San Carlos, CP 37672, Leon, Gto, Mexico
| | - Yeniley Ruiz-Noa
- Department of Medical Sciences, Health Sciences Division, University of Guanajuato, Leon, Campus, 20 de enero #929, Colonia Obregon, CP 37320, Leon, Gto, Mexico
| | - Juana R Garcia-Ramirez
- Department of Pathology, General Hospital Leon, Boulevard Puente Milenio 1001, Colonia Predio San Carlos, CP 37672, Leon, Gto, Mexico
| | - Benjamin Jordan-Perez
- Department of Surgery, General Hospital Leon, Boulevard Puente Milenio 1001, Colonia Predio San Carlos, CP 3767, Leon, Gto, Mexico
| | - Serafin Garnelo-Cabañas
- Department of Surgery, General Hospital Leon, Boulevard Puente Milenio 1001, Colonia Predio San Carlos, CP 3767, Leon, Gto, Mexico
| | - Maria L Lazo de la Vega-Monroy
- Department of Medical Sciences, Health Sciences Division, University of Guanajuato, Leon, Campus, 20 de enero #929, Colonia Obregon, CP 37320, Leon, Gto, Mexico
| | - Karen I Gutierrez-Aguirre
- Department of Medicine and Nutrition, Health Sciences Division, University of Guanajuato, Leon, Campus, Boulevard Puente del Milenio 1001, Colonia Predio San Carlos, CP 37672, Leon, Gto, Mexico
| | - Lorena R Ibarra-Reynoso
- Department of Medical Sciences, Health Sciences Division, University of Guanajuato, Leon, Campus, 20 de enero #929, Colonia Obregon, CP 37320, Leon, Gto, Mexico.
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17
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Francque SM, Marchesini G, Kautz A, Walmsley M, Dorner R, Lazarus JV, Zelber-Sagi S, Hallsworth K, Busetto L, Frühbeck G, Dicker D, Woodward E, Korenjak M, Willemse J, Koek GH, Vinker S, Ungan M, Mendive JM, Lionis C. Non-alcoholic fatty liver disease: A patient guideline. JHEP Rep 2021; 3:100322. [PMID: 34693236 PMCID: PMC8514420 DOI: 10.1016/j.jhepr.2021.100322] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023] Open
Abstract
This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.
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Key Words
- ALD, alcohol-related or alcoholic liver disease
- ASH, alcoholic steatohepatitis
- BMI, body mass index
- CAP, controlled attenuation parameter
- CT, computed tomography
- CVD, cardiovascular disease
- EASD, European Association for the Study of Diabetes
- EASL, European Association for the Study of the Liver
- EASO, European Association for the Study of Obesity
- FIB-4, fibrosis-4 index
- FXR, farnesoid X receptor
- GLP-1 RAs, glucagon-like receptor 1 agonists
- GP, general practitioner
- HCC, hepatocellular carcinoma
- HDL, high-density lipoprotein
- LDL, low-density lipoproteins
- MRE, magnetic resonance elastography
- MRI, magnetic resonance imaging
- NAFL, non-alcoholic fatty liver
- NAFLD, non-alcoholic fatty liver disease
- NASH CRN, NASH Clinical Research Network
- NASH, non-alcoholic steatohepatitis
- NIT, non-invasive test
- SMART, specific, measurable, achievable, relevant, timely
- T1D, type 1 diabetes
- T2D, type 2 diabetes
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Affiliation(s)
- Sven M. Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- InflaMed Centre of Excellence, University of Antwerp, Antwerp, Belgium
- Translational Sciences in Inflammation and Immunology, University of Antwerp, Antwerp, Belgium
| | - Giulio Marchesini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
- Department of Medical and Surgical Sciences, “Alma Mater” University, Bologna, Italy
| | | | | | | | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Spain
| | - Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
- Department of Gastroenterology and Hepatology, The Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Kate Hallsworth
- Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Luca Busetto
- Department of Medicine, University of Padova, Italy
- European Association for the Study of Obesity
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, University of Navarra Clinic, IdiSNA, CIBEROBN, Pamplona, Spain
- European Association for the Study of Obesity
| | - Dror Dicker
- Department of Internal Medicine, Rabin Medical Center Hasharon Hospital, Tikva, Israel
- European Association for the Study of Obesity
| | | | | | | | - Gerardus H. Koek
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Shlomo Vinker
- Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- World Organization of Family Doctors (WONCA)
- European General Practice Research Network (EGPRN)
- Israel Association of Family Physicians, Israel
- Leumit Health Services, Tel Aviv, Israel
| | | | - Juan M. Mendive
- Training Unit of Family Medicine, Catalan Institute of Health, Barcelona, Spain
- European Society for Primary Care Gastroenterology
| | - Christos Lionis
- European Society for Primary Care Gastroenterology
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Greece
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John BV, Khakoo NS, Schwartz KB, Aitchenson G, Levy C, Dahman B, Deng Y, Goldberg DS, Martin P, Kaplan DE, Taddei TH. Ursodeoxycholic Acid Response Is Associated With Reduced Mortality in Primary Biliary Cholangitis With Compensated Cirrhosis. Am J Gastroenterol 2021; 116:1913-1923. [PMID: 33989225 PMCID: PMC8410631 DOI: 10.14309/ajg.0000000000001280] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 03/12/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Patients with cirrhosis and men have been under-represented in most studies examining the clinical benefit of response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). The aim of this study was to study the association of UDCA response and liver-related death or transplantation, hepatic decompensation, and hepatocellular carcinoma (HCC) in patients with PBC cirrhosis. METHODS We conducted a retrospective cohort study of veterans, predominantly men, with PBC and compensated cirrhosis to assess the association of UDCA response with the development of all-cause and liver-related mortality or transplantation, hepatic decompensation, and HCC using competing risk time-updating Cox proportional hazards models. RESULTS We identified 501 subjects with PBC and compensated cirrhosis, including 287 UDCA responders (1,692.8 patient-years [PY] of follow-up) and 214 partial responders (838.9 PY of follow-up). The unadjusted rates of hepatic decompensation (3.8 vs 7.9 per 100 PY, P < 0.0001) and liver-related death or transplantation (3.7 vs 6.2 per 100 PY, P < 0.0001) were lower in UDCA responders compared with partial responders. UDCA response was associated with a lower risk of hepatic decompensation (subhazard ratio [sHR] 0.54, 95% confidence interval [CI] 0.31-0.95, P = 0.03), death from any cause or transplantation (adjusted hazard ratio 0.49, 95% CI 0.33-0.72, P = 0.0002), and liver-related death or transplantation (sHR 0.40, 95% CI 0.24-0.67, P = 0.0004), but not HCC (sHR 0.39, 95% CI 0.60-2.55, P = 0.32). In a sensitivity analysis, the presence of portal hypertension was associated with the highest UDCA-associated effect. DISCUSSION UDCA response is associated with a reduction in decompensation, all-cause, and liver-related death or transplantation in a cohort of predominantly male patients with cirrhosis, with the highest benefit in patients with portal hypertension.
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Affiliation(s)
- Binu V John
- Division of Hepatology, Bruce W Carter VA Medical Center, Miami, FL
| | | | - Kaley B Schwartz
- Division of Hepatology, Bruce W Carter VA Medical Center, Miami, FL
| | | | - Cynthia Levy
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL
| | - Bassam Dahman
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA
| | - Yangyang Deng
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA
| | - David S. Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA
- Division of Gastroenterology and Hepatology, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | - Tamar H. Taddei
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT
- Division of Gastroenterology and Hepatology, VA Connecticut Healthcare System, West Haven, CT
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John BV, Aitcheson G, Schwartz KB, Khakoo NS, Dahman B, Deng Y, Goldberg D, Martin P, Taddei TH, Levy C, Kaplan DE. Male Sex Is Associated With Higher Rates of Liver-Related Mortality in Primary Biliary Cholangitis and Cirrhosis. Hepatology 2021; 74:879-891. [PMID: 33636012 DOI: 10.1002/hep.31776] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/10/2021] [Accepted: 02/01/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS The impact of sex on the postcirrhosis progression of primary biliary cholangitis (PBC) has not been well defined. Prior studies have suggested that men have worse outcomes but present at more advanced stages of fibrosis than women. This observation, however, has been limited by small numbers of men and even fewer patients with cirrhosis. APPROACH AND RESULTS We investigated the association of sex with the development of all-cause and liver-related mortality or transplantation, decompensation, and hepatocellular carcinoma (HCC), using competing-risk time-updating Cox proportional hazards models in a large cohort of predominantly male patients with PBC cirrhosis assembled from the Veterans Health Administration. In a cohort of 532 participants (418 male) with PBC-related cirrhosis with a total follow-up of 3,231.6 person-years (PY) from diagnosis of compensated cirrhosis, male participants had a higher unadjusted rates of death or transplantation (8.5 vs. 3.8 per 100 PY; P < 0.0001), liver-related death or transplantation (5.5 vs. 2.7 per 100 PY; P < 0.0001), decompensation (5.5 vs. 4.0 per 100 PY; P = 0.002), and HCC (0.9 vs. 0.3 per 100 PY; P < 0.0001). After adjusting for confounders, male sex was associated with a higher risk of death or transplantation (adjusted hazard ratio, 1.80; 95% CI, 1.01-3.19; P = 0.046), and liver-related death or transplantation (subhazard ratio, 2.17; 95% CI, 1.15-4.08; P = 0.02). A sensitivity analysis that defined ursodeoxycholic acid response as normalization of alkaline phosphatase and total bilirubin revealed similar findings. CONCLUSIONS In patients with PBC and well-compensated cirrhosis, male sex is associated with a higher risk of both death and liver-related death or transplantation.
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Affiliation(s)
- Binu V John
- Division of HepatologyBruce W Carter VA Medical CenterMiamiFLUSA
| | | | - Kaley B Schwartz
- Division of HepatologyBruce W Carter VA Medical CenterMiamiFLUSA
| | - Nidah S Khakoo
- Department of MedicineJackson Memorial HospitalMiamiFLUSA
| | - Bassam Dahman
- Department of Health Behavior and PolicyVirginia Commonwealth UniversityRichmondVAUSA
| | - Yangyang Deng
- Department of Health Behavior and PolicyVirginia Commonwealth UniversityRichmondVAUSA
| | - David Goldberg
- Division of Digestive Health and Liver DiseasesUniversity of Miami Miller School of MedicineMiamiFLUSA
| | - Paul Martin
- Division of Digestive Health and Liver DiseasesUniversity of Miami Miller School of MedicineMiamiFLUSA
| | - Tamar H Taddei
- Section of Digestive DiseasesYale School of MedicineNew HavenCTUSA.,Division of Gastroenterology and HepatologyVA Connecticut Healthcare SystemWest HavenCTUSA
| | - Cynthia Levy
- Division of Digestive Health and Liver DiseasesUniversity of Miami Miller School of MedicineMiamiFLUSA
| | - David E Kaplan
- Division of Gastroenterology and HepatologyUniversity of PennsylvaniaPhiladelphiaPAUSA.,Division of Gastroenterology and HepatologyCorporal Michael J. Crescenz VA Medical CenterPhiladelphiaPAUSA
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20
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Fuster D, García-Calvo X, Zuluaga P, Bolao F, Muga R. Assessment of liver disease in patients with chronic hepatitis C and unhealthy alcohol use. World J Gastroenterol 2021; 27:3223-3237. [PMID: 34163107 PMCID: PMC8218351 DOI: 10.3748/wjg.v27.i23.3223] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/11/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection and unhealthy alcohol use are major drivers of the burden of liver disease worldwide and commonly co-occur. Assessment of underlying liver damage is a cornerstone of the clinical care of patients with chronic HCV infection and/or unhealthy alcohol use because many of them are diagnosed at advanced stages of disease. Early diagnosis of liver disease before decompensated liver cirrhosis becomes established is essential for treatment with direct acting antivirals and/or abstinence from alcohol consumption, which are the main therapeutic approaches for clinical management. In this review, we discuss current knowledge around the use of non-invasive methods to assess liver disease, such as abdominal ultrasound, controlled attenuation parameter, transient elastography, magnetic resonance imaging, and indices based on serum markers of liver injury.
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Affiliation(s)
- Daniel Fuster
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
| | - Xavier García-Calvo
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
| | - Paola Zuluaga
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
| | - Ferran Bolao
- Department of Internal Medicine, Hospital Universitari Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08907, Spain
| | - Robert Muga
- Department of Internal Medicine, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona 08916, Spain
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21
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Liu SY, Tsai IT, Hsu YC. Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives. Int J Mol Sci 2021; 22:5170. [PMID: 34068269 PMCID: PMC8153142 DOI: 10.3390/ijms22105170] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/07/2021] [Accepted: 05/12/2021] [Indexed: 12/12/2022] Open
Abstract
Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.
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Affiliation(s)
- Szu-Yi Liu
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan; (S.-Y.L.); (I.-T.T.)
| | - I-Ting Tsai
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan; (S.-Y.L.); (I.-T.T.)
- School of Medicine for International Student, I-Shou University, Kaohsiung 82445, Taiwan
| | - Yin-Chou Hsu
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan; (S.-Y.L.); (I.-T.T.)
- School of Medicine for International Student, I-Shou University, Kaohsiung 82445, Taiwan
- School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan
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22
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Buyco DG, Martin J, Jeon S, Hooks R, Lin C, Carr R. Experimental models of metabolic and alcoholic fatty liver disease. World J Gastroenterol 2021; 27:1-18. [PMID: 33505147 PMCID: PMC7789066 DOI: 10.3748/wjg.v27.i1.1] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 11/01/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome (MetS). Because alcohol consumption in NAFLD patients is common, there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease (ALD). Indeed, MetS also significantly contributes to liver injury in ALD patients. This “syndrome of metabolic and alcoholic steatohepatitis” (SMASH) is thus expected to be a more prevalent presentation in liver patients, as the obesity epidemic continues. Several pre-clinical experimental models that couple alcohol consumption with NAFLD-inducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH. These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation, oxidative stress, and the induction of innate immune response. There are significant limitations in the applicability of these models to human disease, such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption. Thus, there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.
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Affiliation(s)
- Delfin Gerard Buyco
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Jasmin Martin
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Sookyoung Jeon
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Royce Hooks
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Chelsea Lin
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Rotonya Carr
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104, United States
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23
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García-Marchena N, Maza-Quiroga R, Serrano A, Barrios V, Requena-Ocaña N, Suárez J, Chowen JA, Argente J, Rubio G, Torrens M, López-Gallardo M, Marco EM, Castilla-Ortega E, Santín LJ, Rodríguez de Fonseca F, Pavón FJ, Araos P. Abstinent patients with alcohol use disorders show an altered plasma cytokine profile: Identification of both interleukin 6 and interleukin 17A as potential biomarkers of consumption and comorbid liver and pancreatic diseases. J Psychopharmacol 2020; 34:1250-1260. [PMID: 32536325 DOI: 10.1177/0269881120928176] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recent studies have demonstrated that alcohol consumption can modulate the immune system by directly activating natural immunity and triggering inflammatory processes in the central nervous system and in peripheral organs, such as the liver and pancreas. Patients with alcohol use disorders have an elevated frequency of comorbid mental disorders and gut diseases (i.e. fatty liver and pancreatitis) that complicate diagnosis, treatment and prognosis. AIMS The present study aims to explore possible associations in circulating plasma cytokine concentrations in abstinent patients diagnosed with alcohol use disorders. METHODS To this end, 85 abstinent subjects with alcohol use disorders from an outpatient setting and 55 healthy subjects were evaluated for both substance and mental disorders. The plasma levels of cytokines interleukin 1 beta, interleukin 4, interleukin 6, interleukin 17A, interferon gamma and tumour necrosis alpha were determined and their association with (a) history of alcohol consumption, (b) psychiatric comorbidity and (c) liver/pancreas comorbidities was explored. RESULTS We found that plasma concentrations of interleukin 1 beta, interleukin 6 and tumour necrosis alpha were increased, whereas plasma concentrations of interleukin 4, interleukin 17A and interferon gamma were decreased in abstinent alcohol use disorder patients as compared with control subjects. Moreover, we found that changes in interleukin 6 and interleukin 17A plasma concentrations in alcohol use disorder patients were associated with the presence of liver and pancreatic diseases. CONCLUSION The present results suggest alcohol use disorder is associated with alterations of plasma cytokines, being interleukin 6 and interleukin 17A potential biomarkers of the presence of comorbidities of digestive organs. The clinical relevance of these findings is discussed in the context of alcohol-induced inflammatory processes.
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Affiliation(s)
- Nuria García-Marchena
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.,Unidad de Adicciones, Servicio de Medicina Interna, Institut Germans Trias i Pujol (IGTP), Badalona, Spain
| | - Rosa Maza-Quiroga
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Antonia Serrano
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Vicente Barrios
- Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.,Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.,IMDEA Food Institute, Madrid, Spain
| | - Nerea Requena-Ocaña
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Juan Suárez
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Julie Ann Chowen
- Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.,Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.,IMDEA Food Institute, Madrid, Spain
| | - Jesús Argente
- Departments of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.,Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.,IMDEA Food Institute, Madrid, Spain
| | - Gabriel Rubio
- Servicio de Psiquiatría, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Marta Torrens
- Institut de Neuropsiquiatria i Addiccions del Parc de Salut Mar, Barcelona, Spain
| | - Meritxell López-Gallardo
- Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Eva María Marco
- Departamento de Fisiología II, Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain
| | - Estela Castilla-Ortega
- Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
| | - Luis Javier Santín
- Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
| | - Fernando Rodríguez de Fonseca
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Francisco Javier Pavón
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.,Unidad de Gestión Clínica del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Pedro Araos
- Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.,Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain
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24
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Velarde-Ruiz Velasco JA, Higuera-de la Tijera MF, Castro-Narro GE, Zamarripa-Dorsey F, Abdo-Francis JM, Aiza Haddad I, Aldana Ledesma JM, Bielsa-Fernández MV, Cerda-Reyes E, Cisneros-Garza LE, Contreras-Omaña R, Reyes-Dorantes A, Fernández-Pérez NJ, García-Jiménez ES, Icaza-Chávez ME, Kershenobich-Stalnikowitz D, Lira-Pedrín MA, Moreno-Alcántar R, Pérez-Hernández JL, Ramos-Gómez MV, Rizo-Robles MT, Solana-Sentíes S, Torre-Delgadillo A. The Mexican consensus on alcoholic hepatitis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:332-353. [PMID: 32532534 DOI: 10.1016/j.rgmx.2020.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/07/2020] [Indexed: 06/11/2023]
Abstract
Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.
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Affiliation(s)
- J A Velarde-Ruiz Velasco
- Servicio de Gastroenterología; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México.
| | - M F Higuera-de la Tijera
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Ciudad de México, México
| | - G E Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - I Aiza Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Estado de México, México
| | - J M Aldana Ledesma
- Servicio de Gastroenterología; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | | | | | | | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología, Pachuca, Hidalgo, México
| | | | | | - E S García-Jiménez
- Servicio de Gastroenterología; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | | | | | - M A Lira-Pedrín
- Servicio de Medicina Interna y Gastroenterología. Hospital y Centro Médico del Prado, Tijuana, Baja California, México
| | - R Moreno-Alcántar
- Unidad Médica de Alta Especialidad, Hospital de Especialidades CMN SXXI, Ciudad de México, México
| | - J L Pérez-Hernández
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Ciudad de México, México; Hospital Central Sur de Alta Especialidad Petróleos Mexicanos, Ciudad de México, México
| | - M V Ramos-Gómez
- Centro Médico Nacional 20 de Noviembre, Ciudad de México, México
| | - M T Rizo-Robles
- Unidad Médica de Alta Especialidad, Hospital de Especialidades CMN SXXI, Ciudad de México, México
| | | | - A Torre-Delgadillo
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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25
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Velarde-Ruiz Velasco J, Higuera-de la Tijera M, Castro-Narro G, Zamarripa-Dorsey F, Abdo-Francis J, Haddad IA, Aldana Ledesma J, Bielsa-Fernández M, Cerda-Reyes E, Cisneros-Garza L, Contreras-Omaña R, Reyes-Dorantes A, Fernández-Pérez N, García-Jiménez E, Icaza-Chávez M, Kershenobich-Stalnikowitz D, Lira-Pedrín M, Moreno-Alcántar R, Pérez-Hernández J, Ramos-Gómez M, Rizo-Robles M, Solana-Sentíes S, Torre-Delgadillo A. The Mexican consensus on alcoholic hepatitis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2020. [DOI: 10.1016/j.rgmxen.2020.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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26
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Sterling SA, Palzes VA, Lu Y, Kline-Simon AH, Parthasarathy S, Ross T, Elson J, Weisner C, Maxim C, Chi FW. Associations Between Medical Conditions and Alcohol Consumption Levels in an Adult Primary Care Population. JAMA Netw Open 2020; 3:e204687. [PMID: 32401315 PMCID: PMC7221504 DOI: 10.1001/jamanetworkopen.2020.4687] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
IMPORTANCE Excessive alcohol consumption is associated with increased incidence of several medical conditions, but few nonveteran, population-based studies have assessed levels of alcohol use across medical conditions. OBJECTIVE To examine associations between medical conditions and alcohol consumption levels in a population-based sample of primary care patients using electronic health record data. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used separate multinomial logistic regression models to estimate adjusted associations between 26 medical conditions and alcohol consumption levels in a sample of 2 720 231 adult primary care patients screened for unhealthy drinking between January 1, 2014, and December 31, 2017, then only among those reporting alcohol use. The study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system that incorporated alcohol screening into its adult primary care workflow. Data were analyzed from June 29, 2018, to February 7, 2020. MAIN OUTCOMES AND MEASURES The main outcome was level of alcohol use, classified as no reported use, low-risk use, exceeding daily limits only, exceeding weekly limits only, or exceeding daily and weekly limits, per National Institute on Alcohol Abuse and Alcoholism guidelines. Other measures included sociodemographic, body mass index, smoking, inpatient and emergency department use, and a dichotomous indicator for the presence of 26 medical conditions in the year prior to the alcohol screening identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis codes. RESULTS Among the 2 720 231 included patients, 1 439 361 (52.9%) were female, 1 308 659 (48.1%) were white, and 883 276 (32.5%) were aged 18 to 34 years. Patients with any of the conditions (except injury or poisoning) had lower odds of drinking at low-risk and unhealthy levels relative to no reported use compared with those without the condition. Among 861 427 patients reporting alcohol use, patients with diabetes (odds ratio [OR], 1.11; 95% CI, 1.08-1.15), hypertension (OR, 1.11; 95% CI, 1.09-1.13), chronic obstructive pulmonary disease (COPD; OR, 1.16; 95% CI, 1.10-1.22), or injury or poisoning (OR, 1.06; 95% CI, 1.04-1.07) had higher odds of exceeding daily limits only; those with atrial fibrillation (OR, 1.12; 95% CI, 1.06-1.18), cancer (OR, 1.06; 95% CI, 1.03-1.10), COPD (OR, 1.15; 95% CI, 1.09-1.20), or hypertension (OR, 1.37; 95% CI, 1.34-1.40) had higher odds of exceeding weekly limits only; and those with COPD (OR, 1.15; 95% CI, 1.07-1.23), chronic liver disease (OR, 1.42; 95% CI, 1.32-1.53), or hypertension (OR, 1.48; 95% CI, 1.44-1.52) had higher odds of exceeding both daily and weekly limits. CONCLUSIONS AND RELEVANCE Findings suggest that patients with certain medical conditions are more likely to have elevated levels of alcohol use. Health systems and clinicians may want to consider approaches to help targeted patient subgroups limit unhealthy alcohol use and reduce health risks.
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Affiliation(s)
- Stacy A. Sterling
- Division of Research, Kaiser Permanente Northern California, Oakland
| | - Vanessa A. Palzes
- Division of Research, Kaiser Permanente Northern California, Oakland
| | - Yun Lu
- Division of Research, Kaiser Permanente Northern California, Oakland
| | | | | | - Thekla Ross
- Division of Research, Kaiser Permanente Northern California, Oakland
| | - Joseph Elson
- The Permanente Medical Group, San Francisco, California
| | - Constance Weisner
- Division of Research, Kaiser Permanente Northern California, Oakland
| | - Clara Maxim
- Division of Research, Kaiser Permanente Northern California, Oakland
| | - Felicia W. Chi
- Division of Research, Kaiser Permanente Northern California, Oakland
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27
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Dash S, Aydin Y, Widmer KE, Nayak L. Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment. J Hepatocell Carcinoma 2020; 7:45-76. [PMID: 32346535 PMCID: PMC7167284 DOI: 10.2147/jhc.s221187] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 03/06/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.
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Affiliation(s)
- Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
- Department of Medicine, Division of Gastroenterology, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA
| | - Kyle E Widmer
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
| | - Leela Nayak
- Southeast Louisiana Veterans Health Care System, New Orleans, LA70119, USA
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Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 513] [Impact Index Per Article: 102.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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Kautz A, Dorner R, Antoni C, Ebert M, Teufel A. Self-testing for liver disease - response to an online liver test questionnaire. Scand J Gastroenterol 2020; 55:67-73. [PMID: 31822163 DOI: 10.1080/00365521.2019.1699600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background: Elevated liver enzymes and chronic liver disease are associated with increased morbidity and mortality. Broad availability of internet questionnaires obtains representative insights into awareness of (chronic) liver disease in the general population. Also, these tools may be used to identify persons and populations at risk to prevent advanced liver disease.Methods: An online questionnaire regarding awareness of liver disease, risk behavior and awareness of own liver tests was implemented online. During 43 months study period, 210,230 participants accessed the online questionnaire. Of these, 117,446 individuals completed the survey. All database access and input were registered and collected in a SQL based database for further evaluation.Results: Awareness of own liver status was lower than expected. About 50.7% of all participants were uncertain about their liver enzyme status. In turn, risk behavior continues to be considerably high as 38.8% of participants stated high-risk behavior for alcohol consumption and 2.2% high-risk substance abuse such as cocaine or heroin. Our questionnaire was predominantly answered by participants under 65 years of age. Participants with high BMI may have been underrepresented.Conclusion: Our study demonstrated the urgent need for improved liver screening, health education regarding risk behavior and improved awareness campaigns on liver disease. Interest of the general population may be presumed as more than 200,000 people accessed our test of their own accord.
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Affiliation(s)
- Achim Kautz
- Liver Aid Project (Leberhilfe Projekt gUG), Cologne, Germany
| | - Rebecca Dorner
- Liver Aid Project (Leberhilfe Projekt gUG), Cologne, Germany
| | - Christoph Antoni
- Division of Clinical Bioinformatics, Division of Hepatology, Department of Medicine II, Heidelberg University, Heidelberg, Germany
| | - Matthias Ebert
- Division of Clinical Bioinformatics, Division of Hepatology, Department of Medicine II, Heidelberg University, Heidelberg, Germany
| | - Andreas Teufel
- Division of Clinical Bioinformatics, Division of Hepatology, Department of Medicine II, Heidelberg University, Heidelberg, Germany
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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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Ventura-Cots M, Ballester-Ferré MP, Ravi S, Bataller R. Public health policies and alcohol-related liver disease. JHEP Rep 2019; 1:403-413. [PMID: 32039391 PMCID: PMC7005647 DOI: 10.1016/j.jhepr.2019.07.009] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 07/23/2019] [Accepted: 07/30/2019] [Indexed: 12/11/2022] Open
Abstract
Alcohol-related liver disease (ALD) represents a major public health problem worldwide. According to the World Health Organization, the highest levels of per capita alcohol consumption are observed in countries of the European Region. Alcohol consumption is also alarmingly increasing in developing countries. ALD is one of the main contributors to the burden of alcohol-attributable deaths and disability. In the United States, severe forms of ALD such alcoholic hepatitis have increased in the last decade and in the United Kingdom, three-quarters of liver-related mortality results from alcohol consumption. Besides genetic factors, there is strong evidence that the amount of alcohol consumed plays a major role in the development of advanced ALD. Establishing effective public health policies is therefore mandatory to reduce the burden of ALD. Since the 90s, major public health institutions and governments have developed a variety of policies in order to reduce the harm caused by excessive drinking. These policies encompass multiple factors, from pricing and taxation to advertising regulation. Measures focused on taxation and price regulation have been shown to be the most effective at reducing alcohol-related mortality. However, there are few studies focused on the effect of public policies on ALD. This review article summarises the factors influencing ALD burden and the role of different public health policies.
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Affiliation(s)
- Meritxell Ventura-Cots
- Center for Liver Diseases, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Samhita Ravi
- Center for Liver Diseases, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ramon Bataller
- Center for Liver Diseases, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA
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Lackner C, Tiniakos D. Fibrosis and alcohol-related liver disease. J Hepatol 2019; 70:294-304. [PMID: 30658730 DOI: 10.1016/j.jhep.2018.12.003] [Citation(s) in RCA: 185] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 12/06/2018] [Accepted: 12/07/2018] [Indexed: 02/06/2023]
Abstract
Histological fibrosis stage is one of the most important prognostic factors in compensated and decompensated alcohol-related liver disease (ALD). Morphological assessment of fibrosis is useful for patient stratification, enabling individualised management, and for evaluation of treatment effects in clinical studies. In contrast to most chronic liver diseases where fibrosis is portal-based, fatty liver disease (FLD) of alcoholic or non-alcoholic aetiology (NAFLD) is associated with a centrilobular pattern of injury which leads to perivenular fibrosis and/or pericellular fibrosis. Progression of FLD drives expansive pericellular fibrosis, linking vascular structures and paving the way for the development of cirrhosis. At the cirrhotic stage, ongoing tissue damage leads to increasing fibrosis severity due to parenchymal loss and proliferation of fibrous scars. Histologic fibrosis staging systems have been devised, based on topography and the extent of fibrosis, for most chronic liver diseases. The utility of histological staging is reflected in different risks associated with individual fibrosis stages which cannot be reliably distinguished by non-invasive fibrosis assessment. In contrast to NAFLD, ALD-specific staging systems that enable the standardised prognostication required for clinical management and trials are lacking. Although morphological similarities between NAFLD and ALD exist, differences in clinical and histological features may substantially limit the utility of established NAFLD-specific staging systems for prognostication in ALD. This review summarises morphological features of fibrosis in ALD and compares them to other chronic liver diseases, particularly NAFLD. ALD-related fibrosis is examined in the context of pathogenetic mechanisms of fibrosis progression, regression and clinical settings that need to be considered in future prognostically relevant ALD staging approaches.
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Affiliation(s)
- Carolin Lackner
- Institute of Pathology, Medical University of Graz, Neue Stiftingtalstraße 6, Graz 8010, Austria.
| | - Dina Tiniakos
- Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; Dept of Pathology, Aretaieion Hospital, Medical School, National & Kapodistrian University of Athens, Vas. Sofias Avenue 76, Athens 11528, Greece
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Affiliation(s)
- Daniel Fuster
- From the Internal Medicine Service, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain (D.F.); and the Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, the Grayken Center for Addiction, Boston Medical Center, and the Department of Community Health Sciences, Boston University School of Public Health - all in Boston ( J.H.S.)
| | - Jeffrey H Samet
- From the Internal Medicine Service, Addiction Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain (D.F.); and the Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston Medical Center and Boston University School of Medicine, the Grayken Center for Addiction, Boston Medical Center, and the Department of Community Health Sciences, Boston University School of Public Health - all in Boston ( J.H.S.)
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Pavlidou E, Mantzorou M, Fasoulas A, Tryfonos C, Petridis D, Giaginis C. Wine: An Aspiring Agent in Promoting Longevity and Preventing Chronic Diseases. Diseases 2018; 6:diseases6030073. [PMID: 30096779 PMCID: PMC6165230 DOI: 10.3390/diseases6030073] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 08/04/2018] [Accepted: 08/06/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Moderate wine consumption is a characteristic of the Mediterranean diet. Studies around the world have shown a beneficial effect of moderate alcohol intake, especially wine, on health. This review aims to critically summarise the most recent studies that investigate the beneficial effects of moderate wine intake on human health. METHODS The PubMed database was comprehensively searched to identify trials published from 2013 to 2018 that investigated the association between moderate wine consumption and health. RESULTS The most recent studies confirm the valuable role of moderate wine consumption, especially red wine, in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, cognitive decline, depression, and cancer. In the meantime, recent studies also highlight the beneficial role of red wine against oxidative stress and in favour of desirable gut bacteria. The beneficial role of red wine has been attributed to its phytochemical compounds, as highlighted by clinical trials, where the effect of red wine has been compared to white wine, non-alcoholic wine, other alcoholic drinks, and water. CONCLUSIONS Moderate wine intake, at 1⁻2 glasses per day as part of the Mediterranean diet, has been positively associated with human health promotion, disease prevention, and disease prognosis.
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Affiliation(s)
- Eleni Pavlidou
- Department of Food Science and Nutrition, University of the Aegean, Myrina, 81400 Lemnos, Greece.
| | - Maria Mantzorou
- Department of Food Science and Nutrition, University of the Aegean, Myrina, 81400 Lemnos, Greece.
| | - Aristeidis Fasoulas
- Department of Food Science and Nutrition, University of the Aegean, Myrina, 81400 Lemnos, Greece.
| | - Christina Tryfonos
- Department of Food Science and Nutrition, University of the Aegean, Myrina, 81400 Lemnos, Greece.
| | - Dimitris Petridis
- Department of Food Technology, Technological Educational Institute of Thessaloniki, 57400 Sindos, Greece.
| | - Constantinos Giaginis
- Department of Food Science and Nutrition, University of the Aegean, Myrina, 81400 Lemnos, Greece.
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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: 570] [Impact Index Per Article: 81.4] [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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Axley P, Ahmed Z, Ravi S, Singal AK. Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review. J Clin Transl Hepatol 2018; 6:79-84. [PMID: 29607308 PMCID: PMC5863002 DOI: 10.14218/jcth.2017.00067] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/14/2017] [Accepted: 11/20/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of liver-related death worldwide. Hepatitis C virus (HCV) infection is a major cause of advanced hepatic fibrosis and cirrhosis, with significantly increased risk for development of HCC. The morbidity and mortality of HCV-related HCC remains high, as rates of HCV cirrhosis continue to increase. The long-term goal of antiviral therapy for chronic HCV is to reduce complications from cirrhosis, including HCC. The advent of new direct-acting antivirals with high rates of virological clearance has revolutionized cure of HCV infection. While the development of HCC in HCV patients who achieve disease sustained virologic response is reduced, these patients remain at risk for HCC, particularly those patients with advanced fibrosis and cirrhosis. This review outlines the epidemiology of HCC in chronic HCV, various mechanisms, risk factors and pathophysiology that contribute to this disease process, screening recommendations, and the available data on the impact of new direct-acting antiviral treatment on the development on HCC.
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Affiliation(s)
- Page Axley
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Zunirah Ahmed
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sujan Ravi
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, AL, USA
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Zhao X, Sun P, Li G, Yi R, Qian Y, Park KY. Polyphenols in Kuding tea help prevent HCl/ethanol-induced gastric injury in mice. Food Funct 2018; 9:1713-1725. [DOI: 10.1039/c7fo01754e] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
We conducted the present study to determine the gastric injury preventive effects of polyphenols in Kuding tea (KTPs) in Kunming (KM) mice through the inhibition of gastric-acid secretion and the protection of the gastric mucosa.
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Affiliation(s)
- Xin Zhao
- Chongqing Collaborative Innovation Center for Functional Food
- Chongqing University of Education
- Chongqing 400067
- P.R. China
- Chongqing Engineering Research Center of Functional Food
| | - Peng Sun
- Chongqing Collaborative Innovation Center for Functional Food
- Chongqing University of Education
- Chongqing 400067
- P.R. China
- Chongqing Engineering Research Center of Functional Food
| | - Guijie Li
- Chongqing Collaborative Innovation Center for Functional Food
- Chongqing University of Education
- Chongqing 400067
- P.R. China
- Chongqing Engineering Research Center of Functional Food
| | - Ruokun Yi
- Chongqing Collaborative Innovation Center for Functional Food
- Chongqing University of Education
- Chongqing 400067
- P.R. China
- Chongqing Engineering Research Center of Functional Food
| | - Yu Qian
- Chongqing Collaborative Innovation Center for Functional Food
- Chongqing University of Education
- Chongqing 400067
- P.R. China
- Chongqing Engineering Research Center of Functional Food
| | - Kun-Young Park
- Chongqing Collaborative Innovation Center for Functional Food
- Chongqing University of Education
- Chongqing 400067
- P.R. China
- Department of Food Science and Biotechnology
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