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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: 30] [Impact Index Per Article: 7.5] [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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Understanding Risk Behaviors of Vietnamese Adults with Chronic Hepatitis B in an Urban Setting. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16040570. [PMID: 30781486 PMCID: PMC6406858 DOI: 10.3390/ijerph16040570] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 01/16/2019] [Accepted: 02/12/2019] [Indexed: 12/16/2022]
Abstract
Cigarette smoking and alcohol consumption can be considered as risk factors that increase the progression of chronic liver disease. Meanwhile, unprotected sex is one of the main causes of hepatitis B infection. This study aimed to explore drinking, smoking, and risky sexual behaviors among people with chronic hepatitis B virus (HBV) in a Vietnamese urban setting, as well as investigating potential associated factors. A cross-sectional study was performed in October 2018 in Viet-Tiep Hospital, Hai Phong, Vietnam. A total of 298 patients who had been diagnosed with chronic hepatitis B reported their smoking status, alcohol use, and sexual risk behavior in the last 12 months. A multivariate logistic regression model was used to identify the associated factors. It was identified that 82.5% of participants never used alcohol. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive result among male patients was 7.4% (0% in female patients). In addition, 14.5% of participants were current smokers and the mean number of cigarettes per day was 7.4 (SD = 3.4). It was found that 35.4% of male patients had sex with two or more sex partners. Furthermore, 66.7% and 74.1% of participants used condoms when having sex with casual partners/one-night stands and sex workers, respectively. There was a positive correlation between monthly drinking and currently smoking. White-collar workers were less likely to have multiple sex partners within the last 12 months. Our study highlights the need for integrating counseling sessions and educational programs with treatment services.
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Trimble G, Zheng L, Mishra A, Kalwaney S, Mir HM, Younossi ZM. Mortality associated with alcohol-related liver disease. Aliment Pharmacol Ther 2013; 38:596-602. [PMID: 23889765 DOI: 10.1111/apt.12432] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Revised: 06/23/2013] [Accepted: 07/07/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Excessive alcohol use has been reported to be responsible for 80 000 annual deaths in the United States. However, the exact cause of death related to the excessive use of alcohol has not been fully explored. AIM To assess the effect of alcoholic liver disease (ALD) on all-cause, liver-related and cardiovascular mortality using population-based data. METHODS Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality Files. Alcohol consumption was estimated as grams per day. Multivariate Cox proportional hazards model was utilised to assess the effects of ALD on follow-up time to mortality from all causes, cardiovascular disease and liver disease. RESULTS A total of 8,306 participants were included [ALD (n = 148)]. Mortality follow-up data were available for a median time of 178.27 months. Participants with ALD had increased risk for liver-related mortality [adjusted hazard ratios or aHR 7.06 (2.09-23.79)], but not for overall mortality [aHR 1.14 (0.70-1.85)] or cardiovascular mortality [aHR 0.61 (0.11-3.25)]. CONCLUSION Alcoholic liver disease increases the risks for liver-related mortality but not for cardiac or overall mortality.
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Affiliation(s)
- G Trimble
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA 22042, USA
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Go VF, Minh NL, Frangakis C, Ha TV, Latkin CA, Sripaipan T, Davis W, Zelaya C, Ngoc NP, Quan VM. Decreased injecting is associated with increased alcohol consumption among injecting drug users in northern Vietnam. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2013; 24:304-11. [PMID: 23332981 PMCID: PMC4774043 DOI: 10.1016/j.drugpo.2012.12.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 12/04/2012] [Accepted: 12/09/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND Reducing injecting frequency may reduce the risk of HIV infection and improve health outcomes among injection drug users (IDUs). However, the reduction of one risk behavior may be associated with an increase in other risk behaviors, including the use of other risk-associated substances. Our objective was to determine if an association exists between a reduction in injecting and level of alcohol use among IDU. METHODS We conducted a longitudinal analysis of data collected for a randomized controlled trial examining the efficacy of a peer education intervention in reducing HIV risk among IDU and their network members in Thai Nguyen, Vietnam. Our analysis included active male injectors (n = 629) who were study participants and attended both baseline and 3-month visits. Frequency of alcohol consumption was assessed as the number of alcoholic drinks in the past 30 days. Change in risk and outcome behaviors was calculated as the difference in frequencies of behaviors between baseline and 3-month follow-up visits. The outcome of interest was concurrent decreased drug injection and increased alcohol consumption. RESULTS The mean difference between baseline and 3-month follow-up of alcohol consumption and injection frequency in the past 30 days was 19.03 drinks (93.68 SD) and 20.22 injections (35.66 SD), respectively. Participants who reported reduced injection frequency were almost three times as likely to report increased alcohol consumption (OR 2.8; 95% CI, 2.0, 4.0). The proportion that both decreased injecting and increased alcohol by any amount in the past 30 days was 35.6%. In multivariate analysis higher education was significantly associated with an increase in alcohol and decrease in injecting of any amount. CONCLUSION Male IDU may be at risk for increasing alcohol consumption when they reduce injection frequency. Interventions with male IDU that encourage reduction of injection may need to review specific strategies to limit alcohol consumption.
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Affiliation(s)
- Vivian F Go
- Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD 21205, USA.
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Lin CW, Lin CC, Mo LR, Chang CY, Perng DS, Hsu CC, Lo GH, Chen YS, Yen YC, Hu JT, Yu ML, Lee PH, Lin JT, Yang SS. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol 2013; 58:730-735. [PMID: 23220252 DOI: 10.1016/j.jhep.2012.11.045] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 11/21/2012] [Accepted: 11/29/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Taiwan has a high prevalence of hepatitis B viral (HBV) infection and hepatocellular carcinoma (HCC) with increasing consumption of alcohol. We investigated the impact of heavy alcohol consumption and HBV infection on HCC in cirrhotic patients. METHODS 966 cirrhotic patients (132 with HBV infection and alcoholism, 632 with HBV infection, and 202 patients with alcoholism) were enrolled between 2000 and 2009 and followed until 2011. The primary end point was newly developed HCC. RESULTS Within the three patient groups (cirrhotic patients with HBV infection and alcoholism, HBV infection alone, and alcoholism alone) 38 (28.8%), 100 (15.8%), and 21 (10.4%) showed newly developed HCC, respectively. The 10-year cumulative (52.8% vs. 39.8% vs. 25.6%, p <0.001) and annual incidences (9.9%, 4.1%, and 2.1%) of HCC were significantly higher in cirrhotic patients with HBV infection and alcoholism than those in patients with HBV infection or alcoholism alone. For patients with HBV infection and alcoholism, baseline serum HBV DNA (OR=16.8, p=0.025), antiviral nucleos(t)ides analogues (NUCs) therapy (OR=0.01, p=0.035), and serum α-fetoprotein (OR=1.18, p=0.045) were risk predictors of HCC by multivariate logistic regression models. The cumulative incidence of HCC was higher in patients with higher baseline serum HBV DNA. Antiviral NUCs therapy reduced the incidence of HCC. CONCLUSIONS Heavy alcohol consumption significantly increased the risk of HCC in HBV-related cirrhotic patients. Elevated baseline serum HBV DNA was a strong risk predictor of HCC and antiviral NUCs therapy reduced the incidence of HCC in cirrhotic patients with HBV infection and alcoholism.
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Affiliation(s)
- Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan
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Younossi ZM, Zheng L, Stepanova M, Venkatesan C, Mir HM. Moderate, excessive or heavy alcohol consumption: each is significantly associated with increased mortality in patients with chronic hepatitis C. Aliment Pharmacol Ther 2013; 37:703-9. [PMID: 23432436 DOI: 10.1111/apt.12265] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2013] [Revised: 02/04/2013] [Accepted: 02/05/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The impact of moderate alcohol consumption on long-term outcomes of chronic hepatitis C (CH-C) infected patients remains controversial. AIM To assess the impact of moderate alcohol consumption on long-term outcomes of CH-C patients using population-based data. METHODS Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES III)-mortality linked files. Alcohol consumption was estimated as grams/day. Multivariate Cox proportional hazards model was utilized to assess the effects of CH-C and alcohol consumption on mortality (all causes, cardiovascular disease, and liver disease). RESULTS A total of 8985 participants were included as the study cohort. Of these, 218 had CH-C. The follow-up time was 162.95 months for CH-C and 178.27 months for controls. CH-C patients had increased risk for both overall mortality and liver-related mortality. CH-C patients with excessive alcohol consumption had even higher risks for overall mortality and liver-related mortality. The risk of overall mortality associated with CH-C increased with moderate alcohol consumption of 1-19 g/day and heavy alcohol consumption ≥30 g/day. CONCLUSION Although chronic hepatitis C is associated with increased risks for overall and liver-related mortality, these risks are even higher for patients consuming moderate and excessive amounts of alcohol.
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Affiliation(s)
- Z M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA 22042, USA.
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Barbero-Becerra VJ, López-Velázquez JA, Sánchez-Valle V, Uribe M, Méndez-Sánchez N. Alcohol effects on liver diseases: good or bad buddy? Ann Hepatol 2012; 11:944-948. [PMID: 23109459 DOI: 10.1016/s1665-2681(19)31422-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
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Lo Re V, Lim JK, Goetz MB, Tate J, Bathulapalli H, Klein MB, Rimland D, Rodriguez-Barradas MC, Butt AA, Gibert CL, Brown ST, Kidwai F, Brandt C, Dorey-Stein Z, Reddy KR, Justice AC. Validity of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study. Pharmacoepidemiol Drug Saf 2011; 20:689-99. [PMID: 21626605 PMCID: PMC3131229 DOI: 10.1002/pds.2148] [Citation(s) in RCA: 134] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2011] [Accepted: 03/21/2011] [Indexed: 12/13/2022]
Abstract
PURPOSE The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS). METHODS Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin ≥ 5.0 g/dL, albumin ≤ 2.0 g/dL, INR ≥ 1.7) recorded 1 year before through 6 months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined. RESULTS Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95%CI, 33%-50%) and 56 (PPV, 28%; 95%CI, 22%-35%) patients, respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95%CI, 47%-79%). One inpatient or ≥2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95%CI, 77%-98%) for confirmed hepatic decompensation events. CONCLUSION An algorithm of 1 inpatient or ≥ 2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts.
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Affiliation(s)
- Vincent Lo Re
- Philadelphia VA Medical Center, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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Mota A, Guedes F, Areias J, Pinho L, Cardoso MF. Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences. Alcohol 2010; 44:149-56. [PMID: 20116194 DOI: 10.1016/j.alcohol.2009.11.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2009] [Revised: 11/04/2009] [Accepted: 11/05/2009] [Indexed: 01/08/2023]
Abstract
Alcohol abuse is an important public health problem. In Portugal with a population of 10 millions of inhabitants, there are around 10% of alcoholics or excessive alcohol drinkers and 1% of chronically infected patients with hepatitis B virus (HBV). To examine the characteristics of patients with higher levels of alcohol consumption and to investigate the association between alcohol consumption and liver damage a total of 298 chronically infected individuals, with HBV genotyped and submitted to liver biopsy, were classified with Child's grading and separated by habits of alcohol intake, less and greater than 20g/day. No significant differences were observed about genotype but genotypes A and D were predominant in both of them. A higher percentage of males (P<.001) were observed in the group with alcohol intake above 20g/day, as well a lower proportion of patients with HBeAg negativity (P< or =.035). In this group, biochemistry parameters, such as alanine aminotransferase (P=.006), aspartate aminotransferase (P=.001), gamma-glutamyl transferase (P<.001) were elevated in a significantly higher proportion than in the other group. The analysis of hematological parameters showed significantly lower values of platelets (P=.042) and mean corpuscular volume (P<.001) and significantly higher values of prothrombin time (P<.001) in the group with higher levels of alcohol consumption. The characteristics of biopsy (P<.001) and Child-Phug's classification (P=.002) revealed more severe results in this group. Logistic regression showed a positive association between liver damage and alcohol intake, increasing with age. In female patients, a strong positive association between alcohol intake and liver damage was also found (odds ratio: 9.379; 95% confidence interval: 0.859-468.422; P = .037); however, the most severe cases were only observed in women older than 45 years. In patients with HBV infection, alcohol is associated with a more severe liver disease. No evidence was found concerning association with HBV genotype.
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Affiliation(s)
- Ana Mota
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal
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Bhattacharjee N, Pathak S, Khuda-Bukhsh AR. Amelioration of carcinogen-induced toxicity in mice by administration of a potentized homeopathic drug, natrum sulphuricum 200. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2009; 6:65-75. [PMID: 18955221 PMCID: PMC2644277 DOI: 10.1093/ecam/nem067] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2006] [Accepted: 05/08/2007] [Indexed: 12/22/2022]
Abstract
To examine if a potentized homeopathic drug, Natrum Sulphuricum 200 (Nat Sulph-200) has protective potentials against hepatocarcinogenesis, liver tumors were induced in mice through chronic feeding of P-dimethylaminoazobenzene (p-DAB; initiator of hepatocarcinogenesis) and phenobarbital (PB; promoter). Mice were divided into five sub-groups: fed normal low protein diet (Gr. I, normal control); fed normal low protein plus alcohol-200 (vehicle of the homeopathic remedy) (Gr. II); fed diet mixed with 0.06% p-DAB plus 0.05% PB (Gr. III); fed diet and carcinogens like Gr.III, plus alcohol 200 (positive control for drug fed mice) (Gr. IV) and fed diet and carcinogens like Gr. III, plus Natrum Sulphuiricum-200 (Gr. V; drug fed). Mice were sacrificed at day 7, 15, 30, 60, 90 and day 120 for study of cytogenetical endpoints like chromosome aberrations (CA), micronuclei (MN), mitotic index (MI) and sperm head anomaly (SHA) and biochemical toxicity parameters like aspartate amino transferase (AST), alanine amino transferase (ALT), acid (AcP) and alkaline (AlkP) phosphatases, lipid peroxidation (LPO) and reduced glutathione (GSH) content. Less number of liver tumors were observed in Gr. V (drug fed) mice. Administration of Nat Sulph 200 reduced genomic damage, activities of AcP, AlkP, AST, ALT, LPO and increased GSH content. Therefore, independent replication of the study by others is encouraged.
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Lee KT, Tsai SM, Wang SN, Lin SK, Wu SH, Chuang SC, Wu SH, Ma H, Tsai LY. Glutathione status in the blood and tissues of patients with virus-originated hepatocellular carcinoma. Clin Biochem 2007; 40:1157-62. [PMID: 17706189 DOI: 10.1016/j.clinbiochem.2007.06.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2007] [Revised: 06/17/2007] [Accepted: 06/21/2007] [Indexed: 12/26/2022]
Abstract
OBJECTIVES Glutathione status can be regarded as the redox status for many diseases. This study was performed to investigate the glutathione status in virus-originated hepatocellular carcinoma (HCC). DESIGN AND METHODS The blood and tissue samples were obtained from 24 patients. Blood samples were also obtained from 137 controls for comparison. RESULTS The GSH level and the ratios of GSH/GSSG and GSH/total glutathione of the blood samples from the patients were significantly lower than those of the controls, while the GSSG values were significantly higher. Meanwhile, levels of GSH and total glutathione, as well as the ratios of GSH/GSSH and GSH/total glutathione, were significantly decreased, whereas GSSG levels were significantly higher, in the HCC tissues than those of the adjacent cancer-free tissues. CONCLUSIONS Glutathione status in the HCC suggested that the antioxidant system is severely impaired, supporting a consistent role of the free radical cytotoxicity in the pathophysiology of the disease.
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Affiliation(s)
- King-Teh Lee
- Division of Hepatobiliary Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Abstract
Liver disease secondary to alcohol ranges from alcoholic fatty liver disease to acute hepatitis to cirrhotic liver disease. It is imperative that alcohol be discontinued to allow for any potential improvement in liver function, with most benefit being seen in the early stages of the disease. Alcoholic liver disease has a profound effect on nutrient intake, nutrition status, and metabolism, contributing to a high prevalence of malnutrition in this population. Early intervention with nutrition therapy may improve response to treatment, alleviate symptoms, and improve quality and quantity of life. In this review, nutrition assessment parameters and medical nutrition therapy goals for alcoholic liver disease are discussed.
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Affiliation(s)
- Sara R DiCecco
- William J. von Liebig Transplant Center, Mayo Clinic Rochester, 201 W. Center Street, Rochester, MN 55902, USA.
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Dunn W, Angulo P, Sanderson S, Jamil LH, Stadheim L, Rosen C, Malinchoc M, Kamath PS, Shah VH. Utility of a new model to diagnose an alcohol basis for steatohepatitis. Gastroenterology 2006; 131:1057-63. [PMID: 17030176 PMCID: PMC2483536 DOI: 10.1053/j.gastro.2006.08.020] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2006] [Accepted: 06/21/2006] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Distinguishing an alcohol basis from a nonalcoholic basis for the clinical and histologic spectrum of steatohepatitic liver disease is difficult because of unreliability of alcohol consumption history. Unfortunately, various biomarkers have had limited utility in distinguishing alcoholic liver disease (ALD) from nonalcoholic fatty liver disease (NAFLD). Thus, the aim of our study was to create and validate a model to diagnose ALD in patients with steatohepatitis. METHODS A cross-sectional cohort study was performed at the Mayo Clinic, Rochester, Minnesota, to create a model using multivariable logistic regression analysis. This model was validated in 3 independent data sets comprising patients of varying severity of steatohepatitis spanning over 10 years. RESULTS Logistic regression identified mean corpuscular volume, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, body mass index, and gender as the most important variables that separated patients with ALD from NAFLD. These variables were used to generate the ALD/NAFLD Index (ANI), with ANI of greater than zero incrementally favoring ALD and ANI of less than zero incrementally favoring a diagnosis of NAFLD, thus making ALD unlikely. ANI had a c-statistic of 0.989 in the derivation sample, and 0.974, 0.989, 0.767 in the 3 validation samples. ANI performance characteristics were significantly better than several conventional and recently proposed biomarkers used to differentiate ALD from NAFLD, including the histopathologic marker protein tyrosine phosphatase 1b, AST/ALT ratio, gamma-glutamyl transferase, and carbohydrate-deficient transferrin. CONCLUSIONS ANI, derived from easily available objective variables, accurately differentiates ALD from NAFLD in hospitalized, ambulatory, and pretransplantation patients and compares favorably with other traditional and proposed biomarkers.
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Affiliation(s)
- Winston Dunn
- Advanced Liver Disease Study Group and Miles and Shirley Fiterman Center for Digestive Diseases at Mayo Clinic, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
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Abstract
PURPOSE OF REVIEW To apprise the reader of advances in 2005 in the epidemiology, pathogenesis, prognosis and treatment of alcoholic liver disease. Alcohol use has declined in developed countries, but the opposite is true elsewhere; alcoholic liver disease is a considerable burden worldwide. RECENT FINDINGS Genetic mechanisms for alcoholic liver disease are being discovered in addition to aggravating cofactors, such as hepatitis C, obesity and iron overload, and ameliorating ones, like coffee and tea drinking. The involvement of the innate immune system and the mechanisms of apoptosis in alcoholic liver disease are better appreciated, especially the emerging role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Steroid use and nutrition for alcoholic hepatitis are being refined, and the validity of the model for end-stage liver disease (MELD) score in predicting the outcome of alcoholic liver disease is upheld. Recidivism after liver transplantation for alcoholic liver disease adversely impacts long-term survival. SUMMARY Inroads are being made into the genetics of alcoholic liver disease and new phenomena are being uncovered in its pathogenesis, but safe and effective therapies for both alcoholic hepatitis and alcoholic cirrhosis are still wanting.
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Affiliation(s)
- Adrian Reuben
- Liver Service, Division of Gastroenterology/Hepatology and Liver Transplant Program, Medical University of South Carolina, Charleston, 29425, USA.
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Karaa A, Kamoun WS, Clemens MG. Chronic ethanol sensitizes the liver to endotoxin via effects on endothelial nitric oxide synthase regulation. Shock 2006; 24:447-54. [PMID: 16247331 DOI: 10.1097/01.shk.0000180616.13941.7d] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In vivo studies have shown that chronic alcohol consumption sensitizes the liver to endotoxemic shock, leading to liver microcirculation disruption. In the present study, we investigated the molecular mechanisms involved, focusing on endothelial nitric oxide synthase (eNOS) activity and regulation, which represents one of the major vasodilatory pathways. Male Sprague-Dawley rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks. Priming effects of ethanol were studied in a model with or without a 24-h LPS treatment (1 mg/kg body weight). At the end of the diet, liver tissue was harvested for western blot, reverse transcriptase-PCR, histological analysis, and immunostaining and blood for serum alanine aminotransferase analysis. Chronic ethanol and LPS alone induced a mild hepatitis and infiltration, respectively. Combined, LPS and chronic ethanol feeding showed a synergistic effect on the liver, leading to extensive steatohepatitis with extensive focal necrosis associated with significantly higher levels of serum ALT. Chronic ethanol and LPS significantly inhibited eNOS activity, but exerted their effects through different mechanisms. Caveolin-1, an eNOS inhibitory protein, was upregulated after LPS and chronic alcohol consumption. Additionally, chronic alcohol consumption down-regulated endothelin B receptor, eNOS protein levels, and eNOS phosphorylation. In conclusion, chronic ethanol consumption and LPS share a similar pathophysiology and both lead to the impairment of eNOS activity, but through distinct molecular mechanisms. The presence of focal necrosis in a mild stress model could provide a good animal study to investigate the advanced stages of alcoholic liver diseases.
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Affiliation(s)
- Amel Karaa
- Department of Biology, University of North Carolina, Charlotte, North Carolina 28223, USA
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