PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis.

PubMed

Burza, Maria Antonella; Molinaro, Antonio; Attilia, Maria Luisa; Rotondo, Claudia; Attilia, Fabio; Ceccanti, Mauro; Ferri, Flaminia; Maldarelli, Federica; Maffongelli, Angela; De Santis, Adriano; Attili, Adolfo Francesco; Romeo, Stefano; Ginanni Corradini, Stefano

2014-04-01

Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at-risk alcohol consumption are available. Moreover, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross-sectional studies. The aim of this study was to investigate the role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence. A total of 384 at-risk alcohol drinkers were retrospectively examined. The association among age at onset of at-risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested. A higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset of at-risk alcohol consumption and PNPLA3 148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18-3.50), P-value < 0.001; 1.53(1.07-2.19), P-value = 0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53-6.00) vs. 1.61(1.09-2.38). Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence. © 2013 The Authors. Liver International published by John Wiley & Sons Ltd.

Alcohol Demand, Future Orientation, and Craving Mediate the Relation Between Depressive and Stress Symptoms and Alcohol Problems.

PubMed

Soltis, Kathryn E; McDevitt-Murphy, Meghan E; Murphy, James G

2017-06-01

Elevated depression and stress have been linked to greater levels of alcohol problems among young adults even after taking into account drinking level. This study attempts to elucidate variables that might mediate the relation between symptoms of depression and stress and alcohol problems, including alcohol demand, future time orientation, and craving. Participants were 393 undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2 binge-drinking episodes (4/5+ drinks for women/men, respectively) in the previous month. Participants completed self-report measures of stress and depression, alcohol demand, future time orientation, craving, and alcohol problems. In separate mediation models that accounted for gender, race, and weekly alcohol consumption, future orientation and craving significantly mediated the relation between depressive symptoms and alcohol problems. Alcohol demand, future orientation, and craving significantly mediated the relation between stress symptoms and alcohol problems. Heavy-drinking young adults who experience stress or depression are likely to experience alcohol problems, and this is due in part to elevations in craving and alcohol demand, and less sensitivity to future outcomes. Interventions targeting alcohol misuse in young adults with elevated levels of depression and stress should attempt to increase future orientation and decrease craving and alcohol reward value. Copyright © 2017 by the Research Society on Alcoholism.

Alcohol Demand, Future Orientation, and Craving Mediate the Relation Between Depressive and Stress Symptoms and Alcohol Problems

PubMed Central

Soltis, Kathryn E.; McDevitt-Murphy, Meghan; Murphy, James G.

2017-01-01

Background Elevated depression and stress have been linked to greater levels of alcohol problems among young adults even after taking into account drinking level. The current study attempts to elucidate variables that might mediate the relation between symptoms of depression and stress and alcohol problems, including alcohol demand, future time orientation, and craving. Methods Participants were 393 undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2 binge drinking episodes (4/5+ drinks for women/men, respectively) in the previous month. Participants completed self-report measures of stress and depression, alcohol demand, future time orientation, craving, and alcohol problems. Results In separate mediation models that accounted for gender, race, and weekly alcohol consumption, future orientation and craving significantly mediated the relation between depressive symptoms and alcohol problems. Alcohol demand, future orientation, and craving significantly mediated the relation between stress symptoms and alcohol problems. Conclusions Heavy drinking young adults who experience stress or depression are likely to experience alcohol problems and this is due in part to elevations in craving and alcohol demand, and less sensitivity to future outcomes. Interventions targeting alcohol misuse in young adults with elevated levels of depression and stress should attempt to increase future orientation and decrease craving and alcohol reward value. PMID:28401985

The effects of the 2006 Russian alcohol policy on alcohol-related mortality: an interrupted time series analysis.

PubMed

Pridemore, William Alex; Chamlin, Mitchell B; Kaylen, Maria T; Andreev, Evgeny

2014-01-01

The aim of this study was to determine the impact of a set of 2006 Russian alcohol policies on alcohol-related mortality in the country. We used autoregressive integrated moving average interrupted time series techniques to model the impact of the policy on the number of sex-specific monthly deaths of those aged 15+ years due to alcohol poisoning, alcoholic cardiomyopathy, alcoholic liver cirrhosis, and alcohol-related mental and behavioral disorders. The time series began in January 2000 and ended in December 2010. The alcohol policy was implemented in January 2006. The alcohol policy resulted in a significant gradual and sustained decline in male deaths due to alcohol poisoning (ωo = -92.631, p < 0.008, δ1 = 0.883, p < 0.001) and in significant immediate and sustained declines in male (ω0 = -63.20, p < 0.05) and female (ω0 = -64.28, p < 0.005) deaths due to alcoholic liver cirrhosis. The 2006 suite of alcohol policies in Russia was responsible for an annual decline of about 6,700 male alcohol poisoning deaths and about 760 male and about 770 female alcoholic liver cirrhosis deaths. Without the alcohol policy, male alcohol poisoning deaths would have been 35% higher and male and female alcoholic liver cirrhosis deaths would have been 9 and 15% higher, respectively. We contextualize our findings in relation to declining mortality in Russia and to results from recent studies of the impact of this law on other causes of death. Copyright © 2013 by the Research Society on Alcoholism.

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data.

PubMed

Otete, Harmony; Deleuran, Thomas; Fleming, Kate M; Card, Tim; Aithal, Guru P; Jepsen, Peter; West, Joe

2018-04-17

Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and

Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis.

PubMed

Thiele, Maja; Detlefsen, Sönke; Sevelsted Møller, Linda; Madsen, Bjørn Stæhr; Fuglsang Hansen, Janne; Fialla, Annette Dam; Trebicka, Jonel; Krag, Aleksander

2016-01-01

Alcohol abuse causes half of all deaths from cirrhosis in the West, but few tools are available for noninvasive diagnosis of alcoholic liver disease. We evaluated 2 elastography techniques for diagnosis of alcoholic fibrosis and cirrhosis; liver biopsy with Ishak score and collagen-proportionate area were used as reference. We performed a prospective study of 199 consecutive patients with ongoing or prior alcohol abuse, but without known liver disease. One group of patients had a high pretest probability of cirrhosis because they were identified at hospital liver clinics (in Southern Denmark). The second, lower-risk group, was recruited from municipal alcohol rehabilitation centers and the Danish national public health portal. All subjects underwent same-day transient elastography (FibroScan), 2-dimensional shear wave elastography (Supersonic Aixplorer), and liver biopsy after an overnight fast. Transient elastography and 2-dimensional shear wave elastography identified subjects in each group with significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) with high accuracy (area under the curve ≥0.92). There was no difference in diagnostic accuracy between techniques. The cutoff values for optimal identification of significant fibrosis by transient elastography and 2-dimensional shear wave elastography were 9.6 kPa and 10.2 kPa, and for cirrhosis 19.7 kPa and 16.4 kPa. Negative predictive values were high for both groups, but the positive predictive value for cirrhosis was >66% in the high-risk group vs approximately 50% in the low-risk group. Evidence of alcohol-induced damage to cholangiocytes, but not ongoing alcohol abuse, affected liver stiffness. The collagen-proportionate area correlated with Ishak grades and accurately identified individuals with significant fibrosis and cirrhosis. In a prospective study of individuals at risk for liver fibrosis due to alcohol consumption, we found elastography to be an excellent tool for diagnosing liver

Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study

PubMed Central

Marot, Astrid; Henrion, Jean; Knebel, Jean-François; Moreno, Christophe

2017-01-01

Background Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear. Aim To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death. Methods Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78). Results At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis. Conclusion Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis. PMID:29077714

Complications Requiring Hospital Admission and Causes of In-Hospital Death over Time in Alcoholic and Nonalcoholic Cirrhosis Patients.

PubMed

Kim, Hee Yeon; Kim, Chang Wook; Choi, Jong Young; Lee, Chang Don; Lee, Sae Hwan; Kim, Moon Young; Jang, Byoung Kuk; Wo, Hyun Young

2016-01-01

Data on the epidemiology of alcoholic cirrhosis, especially in Asian countries, are limited. We compared the temporal evolution of patterns of alcoholic and nonalcoholic cirrhosis over the last decade. We retrospectively examined the inpatient datasets of five referral centers during 2002 and 2011. The study included patients who were admitted due to specific complications of liver cirrhosis. We compared the causes of hospital admissions and in-hospital deaths between patients with alcoholic and nonalcoholic cirrhosis. Among the included 2,799 hospitalizations (2,165 patients), 1,496 (1,143 patients) were from 2002, and 1,303 (1,022 patients) were from 2011. Over time, there was a reduction in the rate of hepatic encephalopathy (HE) as a cause of hospitalization and an increase in the rate of hepatocellular carcinoma. Deaths that were attributable to HE or spontaneous bacterial peritonitis (SBP) significantly decreased, whereas those due to hepatorenal syndrome (HRS) significantly increased over time in patients with alcoholic cirrhosis. However, in patients with nonalcoholic cirrhosis, hepatic failure and HRS remained the principal causes of in-hospital death during both time periods. The major causes of in-hospital deaths have evolved from acute cirrhotic complications, including HE or SBP to HRS in alcoholic cirrhosis, whereas those have remained unchanged in nonalcoholic cirrhosis during the last decade.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis.

PubMed

Atla, Pradeep R; Sheikh, Muhammad Y; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher's exact and Student's t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4-8.1) as predictors for readmissions among Hispanics. CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis

PubMed Central

Atla, Pradeep R.; Sheikh, Muhammad Y.; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage. PMID:27708520

Personality and Alcohol-Related Outcomes among Mandated College Students: Descriptive Norms, Injunctive Norms, and College-Related Alcohol Beliefs as Mediators

PubMed Central

Pearson, Matthew R.; Hustad, John T. P.

2014-01-01

The present study examined three alcohol-perception variables (descriptive norms, injunctive norms, and college-related alcohol beliefs) as mediators of the predictive effects of four personality traits (impulsivity, sensation seeking, anxiety sensitivity, and hopelessness) on alcohol use and alcohol-related consequences in a sample of mandated college students (n = 875). Our findings replicated several findings of a previous study of incoming freshman college students (Hustad et al., in press) in that impulsivity and hopelessness had direct effects on alcohol-related problems, sensation seeking and impulsivity had indirect effects on alcohol-related outcomes via college-related alcohol beliefs, and college-related alcohol beliefs predicted both alcohol use and alcohol-related problems. We discuss the implications of our findings for global college student interventions as well as personality-targeted interventions. PMID:24589869

Hepatocellular Carcinoma in the Absence of Cirrhosis in US Veterans is Associated with Non-Alcoholic Fatty Liver Disease

PubMed Central

Mittal, Sahil; El-Serag, Hashem B.; Sada, Yvonne H.; Kanwal, Fasiha; Duan, Zhigang; Temple, Sarah; May, Sarah B.; Kramer, Jennifer R.; Richardson, Peter A.; Davila, Jessica A.

2015-01-01

Background & Aims Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a US population. Methods We identified a national cohort of 1500 patients with verified HCC during 2005–2010 in the US Veterans Administration (VA), and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), based on findings from histologic analyses, laboratory test results, markers of fibrosis from non-invasive tests, and imaging features. Results A total of 43 (2.9%) of the 1500 patients with HCC had level 1 evidence for no cirrhosis and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared to patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have HCV infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4–8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1–7.8) had more than a 5-fold risk of having HCC in the absence of cirrhosis, compared to patients with HCV-related HCC. Conclusions Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors HCC in the absence of cirrhosis. PMID:26196445

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is cryptogenic cirrhosis different from NASH cirrhosis?

PubMed

Thuluvath, Paul J; Kantsevoy, Sergey; Thuluvath, Avesh J; Savva, Yulia

2018-03-01

We hypothesized that patients currently diagnosed with cryptogenic cirrhosis (CC) have truly 'cryptogenic' liver disease, which is unlikely to have evolved from NASH. The aim of this study is to characterize patients with CC, and compare their characteristics to patients with cirrhosis of other etiologies. To investigate this, we compared the clinical characteristics of adults with CC (n = 7,999) to those with cirrhosis caused by non-alcoholic steatohepatitis (NASH) (n = 11,302), alcohol (n = 21,714) and autoimmune hepatitis (n = 3,447), using the UNOS database from 2002-16. We performed an age, gender and year of listing matched comparison of CC and NASH (n = 7,201 in each group), and also stratified patients by the presence of obesity or diabetes mellitus (DM). From 2002 to 2016, patients listed with a diagnosis of NASH increased from about 1% to 16% while CC decreased from 8% to 4%. A logistic regression model using the entire United Network for Organ Sharing data (n = 138,021) suggested that the strongest predictors of NASH were type 2 DM, obesity, age ≥60 years, female gender and white race. Type 2 DM was more common in patients with NASH (53%) than those with CC (29%), alcoholic cirrhosis (16%) and autoimmune hepatitis (16%), and obesity was more common in NASH (65.3%) compared to the other three groups (33-42%). There were more white individuals (82.3%) in the NASH group and a lower prevalence of black, Hispanic and Asian individuals, compared to the other three groups. Hepatocellular carcinoma was more commonly seen in NASH (19% vs. 9-13% in the other groups) and this is not influenced by obesity and type 2 DM. The differences between CC and NASH remained unchanged even when two groups were matched for age, gender and year of listing, or when stratified by the presence or absence of obesity or type 2DM. Based on risk perspectives, CC should not be equated with the term 'NASH cirrhosis'. We hypothesized that cryptogenic cirrhosis

Drinking-and-Driving-Related Cognitions Mediate the Relationship Between Alcohol Demand and Alcohol-Impaired Driving.

PubMed

Amlung, Michael; Morris, David H; Hatz, Laura E; Teeters, Jenni B; Murphy, James G; McCarthy, Denis M

2016-07-01

Elevated behavioral economic demand for alcohol has been shown to be associated with drinking and driving in college students. The present study sought to clarify the underlying mechanisms of this relationship by examining whether drinking-and-driving-related cognitions (e.g., attitudes, perceptions, and normative beliefs) mediate the association between alcohol demand and drinking and driving. A total of 134 young adult social drinkers completed an alcohol purchase task and measures of perceived dangerousness of drinking and driving, normative beliefs about drinking and driving, and perceived driving limit (i.e., perceived number of drinks one could consume and still drive safely). The frequency of drinking and driving in the past year was assessed via self-report. Individuals who reported drinking and driving exhibited greater alcohol demand (intensity, Omax, and elasticity) compared with those who did not engage in drinking and driving. Increased demand was also correlated with more favorable drinking-and-driving cognitions. Indirect effects tests revealed that perceived driving limit partially mediated the relationship between alcohol demand and drinking-and-driving behavior, even after accounting for drinking level, sex, and delay discounting. These findings provide further support for the utility of behavioral economic theory in understanding drinking-and-driving behavior. In particular, they provide evidence for one mechanism-drinking-and-driving-related cognitions-by which alcohol demand influences drinking and driving. Additional research using longitudinal and experimental designs is required to confirm this model and to identify other potential mediators.

The risk of cirrhosis in non-alcohol drinkers is greater in female than male betel nut chewers.

PubMed

Chu, Yu-Hua; Wang, Lee; Ko, Pei-Chieh; Lan, Shou-Jen; Liaw, Yung-Po

2018-02-02

The association of betel nut with liver cirrhosis among alcohol drinkers has been clearly shown. However, very few studies have shown such an association among non-alcohol drinkers. The aim of this study was to assess the relationship between betel nut chewing and cirrhosis among non-alcohol drinkers. This study retrospectively analyzed data retrieved from the 2012 Adult Preventive Medical Services and the National Health Insurance Research Datasets in Taiwan. Participants' information included physical examination and lifestyle, alongside laboratory tests. Betel nut chewers were grouped into three categories: never, occasional and frequent. Diseases were diagnosed using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Initially, 1573024 adults aged 40 years and above who engaged in the free adult preventive medical services in 2012 were recruited. However, only 1065246 of them were included in the analysis. Chi-square test and logistic regression were used for the analyses. After multivariable adjustments, there were significant relationships between cirrhosis and betel nut chewing in both sexes (P-trend < 0.0001). The risk of cirrhosis was greater in females than males. The odds ratios of cirrhosis in occasional and frequent female chewers were respectively 2.91; 95% C.I: 1.75-4.83 and 3.06; 95% C.I: 1.69-5. However, they were respectively 1.76; 95% C.I: 1.47-2.10 and 2.32; 95% C.I: 1.90-2.85 in occasional and frequent male chewers. This study demonstrated significant relationships between betel nut chewing and cirrhosis in both male and female non-alcohol drinkers. The risk of cirrhosis was greater in female than male chewers.

[Ecological correlation between consumption of alcoholic beverages and liver cirrhosis mortality in Mexico].

PubMed

Narro-Robles, J; Gutiérrez-Avila, J H

1997-01-01

To determine the correlation between alcohol consumption and mortality from liver cirrhosis in Mexico. Analysis of the ecological correlation between the patterns of alcohol consumption determined by the National Addiction Survey in 1993 and mortality by liver cirrhosis, in the period between 1971-1993, in the eight regions in which the country was divided. To determine level of correlation, the Pearson and Spearman coefficients were calculated. Significant correlations were only found with the prevalence of spirits and pulque drinkers; with beer drinkers the correlation was negative. The correlation with pulque is interesting, since pulque consumption is considered to be low scale in some rural areas. The negative correlation with beer may indicate that beer drinking is nor a good indicator of alcoholism. Results, though limited to the possibilities of an ecological study, reveal the necessity of effective actions in the regions where spirits and pulque are consumed in excess.

Impulsivity-related traits, college alcohol beliefs, and alcohol outcomes: Examination of a prospective multiple mediation model among college students in Spain, Argentina, and USA.

PubMed

Bravo, Adrian J; Pearson, Matthew R; Pilatti, Angelina; Read, Jennifer P; Mezquita, Laura; Ibáñez, Manuel I; Ortet, Generós

2018-06-01

The present study examined (both cross-sectionally and prospectively) the mediational role of college alcohol beliefs in the relationship between impulsivity-related traits and alcohol outcomes (i.e., alcohol use and negative consequences) among college student drinkers from the United States (U.S.), Spain, and Argentina. A sample of 1429 (U.S. = 733, Spain = 292, Argentina = 404) drinkers (at least one drinking episode within the previous month) completed the baseline survey, and 242 drinkers completed the follow-up. To test study aims, a cross-sectional model was first employed to examine whether the proposed double-mediated paths (i.e., each dimension of impulsivity → college alcohol beliefs → alcohol use → negative alcohol-related consequences) extends across samples with different cultural backgrounds (i.e., structural invariance testing). A longitudinal model was then conducted to assess if college alcohol beliefs prospectively mediate the associations between trait impulsivity and alcohol outcomes. College alcohol beliefs were concurrently and prospectively associated with both greater alcohol use and increased number of negative alcohol-related consequences. These internalized beliefs about college student drinking culture significantly mediated the effects of several distinct impulsivity-related traits on alcohol-related outcomes including urgency (positive and negative), sensation seeking, and perseverance. These findings were invariant across gender and across three countries (Argentina, Spain, and the U.S.). Our findings highlight the modulatory role of cognitive factors on problematic alcohol use among college students with different cultural backgrounds. Our results suggest that, despite the cultural differences exhibited by these three countries, the unique and mediational effects of college alcohol beliefs appear relatively universal. Copyright © 2018 Elsevier Ltd. All rights reserved.

Relationships between serum selenium and zinc concentrations versus profibrotic and proangiogenic cytokines (FGF-19 and endoglin) in patients with alcoholic liver cirrhosis.

PubMed

Prystupa, Andrzej; Kiciński, Paweł; Luchowska-Kocot, Dorota; Błażewicz, Anna; Kurys-Denis, Ewa; Niedziałek, Jarosław; Sak, Jarosław; Panasiuk, Lech

2017-09-21

Liver cirrhosis is a disease involving the liver parenchyma, which is characterised by fibrosis and impaired architectonics of the parenchyma with regenerative nodules. The aim of the study was to determine the relationship between stage of alcoholic liver cirrhosis, concentrations of selenium, zinc and profibrotic and proangiogenic cytokines (FGF-19, ENG). The study included 99 patients with alcoholic cirrhosis and 20 healthy subjects. Ion chromatography with UV/VIS detection was used for determination of zinc ions in the previously mineralized serum samples. The measurements of selenium were performed with the ContrAA700 high-resolution continuum source graphite tube atomic absorption spectrometer. ELISA was used to determine concentration of FGF-19 and ENG in serum samples. Concentrations of zinc and selenium were significantly decreased in cirrhotic patients (p<0.001 for both). The highest concentration of FGF-19 was found in Child-Pugh stage C liver cirrhosis patients (806.9±650.3 pg/ml), and was significantly higher than observed in controls (p=0.005) and stage A patients (compensated cirrhosis) (p=0.02). The highest concentration of ENG was demonstrated in the control group (3.24±148 ng/ml) while the lowest in patients with decompensated cirrhosis (7.32±5.39 ng/ml and 7.92±4.18 ng/ml for stage B and C; p=0.03 and p=0.02, respectively). The use of the multiple-variable model demonstrated that the independent factors affecting the concentration of ENG were the concentration of bilirubin (p=0.02), INR (p=0.01) and duration of alcohol abuse (p=0.02). The independent determinants of FGF-19 concentrations were found to be the stage (severity) of liver cirrhosis (p=0.04) and INR (p=0.03). Concentrations of zinc and selenium in serum of patients with alcoholic liver cirrhosis are not independently related to concentrations of FGF-19 and ENG.

ALCOHOLIC VERSUS NONALCOHOLIC CIRRHOSIS IN A RANDOMIZED CONTROLLED TRIAL OF EMERGENCY THERAPY OF BLEEDING VARICES

PubMed Central

Orloff, Marshall J.; Isenberg, Jon I.; Wheeler, Henry O.; Haynes, Kevin S.; Jinich-Brook, Horacio; Rapier, Roderick; Vaida, Florin; Hye, Robert J.; Orloff, Susan L.

2010-01-01

Background It has been proposed that portal-systemic shunts be avoided in alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than in nonalcoholics. We examined this issue in a randomized controlled trial. Methods 211 unselected, consecutive patients with cirrhosis and bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n=106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within 8 hours. EST failure was treated by rescue PCS. 10-yr follow-up was 96%. Results Results strongly favored EPCS over EST (p<0.001). Among EPCS patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent control of bleeding 100% vs. 100%; (2) 5-yr survival 71% vs.78%; (3) encephalopathy 14% vs. 19%; (4) yearly charges $38,300 vs. $43,000. Conclusions EPCS results were similar in alcoholic and nonalcoholic cirrhotics. EPCS is an effective first line emergency treatment in all forms of cirrhosis, including alcoholic. PMID:21195430

Discrimination and alcohol-related problems among college students: a prospective examination of mediating effects.

PubMed

Hatzenbuehler, Mark L; Corbin, William R; Fromme, Kim

2011-06-01

Discrimination is a risk factor for health-risk behaviors, including alcohol abuse. Far less is known about the mechanisms through which discrimination leads to alcohol-related problems, particularly during high-risk developmental periods such as young adulthood. The present study tested a mediation model using prospective data from a large, diverse sample of 1539 college students. This model hypothesized that discrimination would be associated with established cognitive (positive alcohol expectancies) and affective (negative affect and coping motives) risk factors for alcohol-related problems, which would account for the prospective association between discrimination and alcohol problems. Structural equation modeling indicated that discrimination was associated cross-sectionally with negative affect and more coping motives for drinking, but not with greater alcohol expectancies. Coping motives mediated the prospective relationship between discrimination and alcohol-related problems. Additionally, results indicated significant indirect effects from discrimination to alcohol-related problems through negative affect and coping motives. These associations were evident for multiple groups confronting status-based discrimination, including women, racial/ethnic minorities, and lesbian/gay/bisexual individuals. This study identified potential affective mechanisms linking discrimination to alcohol-related problems. Results suggest several avenues for prevention and intervention efforts with individuals from socially disadvantaged groups. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The Role of Alcohol Perceptions as Mediators Between Personality and Alcohol-Related Outcomes Among Incoming College-Student Drinkers

PubMed Central

Hustad, John T. P.; Pearson, Matthew R.; Neighbors, Clayton; Borsari, Brian

2014-01-01

After high school, college students escalate their drinking at a faster rate than their noncollege-attending peers, and alcohol use in high school is one of the strongest predictors of alcohol use in college. Therefore, an improved understanding of the role of predictors of alcohol use during the critical developmental period when individuals transition to college has direct clinical implications to reduce alcohol-related harms. We used path analysis in the present study to examine the predictive effects of personality (e.g., impulsivity, sensation seeking, hopelessness, and anxiety sensitivity) and three measures of alcohol perception: descriptive norms, injunctive norms, and perceptions regarding the perceived role of drinking in college on alcohol-related outcomes. Participants were 490 incoming freshmen college students. Results indicated that descriptive norms, injunctive norms, and the role of drinking largely mediated the effects of personality on alcohol outcomes. In contrast, both impulsivity and hopelessness exhibited direct effects on alcohol-related problems. The perceived role of drinking was a particularly robust predictor of outcomes and mediator of the effects of personality traits, including sensation seeking and impulsivity on alcohol outcomes. The intertwined relationships observed in this study between personality factors, descriptive norms, injunctive norms, and the role of drinking highlight the importance of investigating these predictors simultaneously. Findings support the implementation of interventions that target these specific perceptions about the role of drinking in college. PMID:24467197

Risk of Depressive Disorder following Non-Alcoholic Cirrhosis: A Nationwide Population-Based Study

PubMed Central

Hu, Li-Yu; Yeh, Chiu-Mei; Chen, Mu-Hong; Tsai, Chia-Fen; Chiang, Huey-Ling; Hung, Yi-Ping; Su, Vincent Yi-Fong; Hu, Yu-Wen; Su, Tung-Ping; Chen, Pan-Ming; Hung, Jeng-Hsiu; Liu, Chia-Jen; Huang, Min-Wei

2014-01-01

Background & Aims To evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD). Methods We conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients. Results During the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57–1.98, P<.001). After adjusting for age, sex, and comorbidities, non-alcoholic cirrhotic patients were 1.75 times more likely to develop depressive disorders (95% CI, 1.56–1.96, P<.001) compared with the control patients. The hazard ratios for patients younger than 60 years old (1.31) and female (1.25) indicated that each is an independent risk factor for depressive disorders in non-alcoholic cirrhotic patients. Conclusions The likelihood of developing depressive disorders is greater among non-alcoholic cirrhotic patients than among patients without cirrhosis. Symptoms of depression should be sought in patients with cirrhosis. PMID:24533141

A mediational model of racial discrimination and alcohol-related problems among african american college students.

PubMed

Boynton, Marcella H; O'Hara, Ross E; Covault, Jonathan; Scott, Denise; Tennen, Howard

2014-03-01

Racial discrimination has been identified as an important predictor of alcohol-related outcomes for African Americans. The goal of the current study was to extend previously found links between lifetime discrimination, alcohol use, and alcohol problems as well as to elucidate the affective mechanisms underlying these associations, as moderated by gender. A multiple-groups structural equation model was computed using survey data collected from 619 students from a historically Black college/university. The final model provided excellent fit to the data, explaining 6% of the variance in alcohol consumption and 37% of the variance in alcohol problems. Discrimination was a significant predictor of alcohol-related problems but not, by and large, level of use. For men, anger-but not discrimination-specific anger-was a significant partial mediator of the link between discrimination and both alcohol use and alcohol problems. Depression partially mediated the link between discrimination and alcohol problems for both men and women. The results suggest that, for African Americans whose drinking leads to drinking-related problems, discrimination and poor affective self-regulation are highly relevant and predictive factors, especially for men.

QT Interval Prolongation and QRS Voltage Reduction in Patients with Liver Cirrhosis.

PubMed

Cichoż-Lach, Halina; Tomaszewski, Michał; Kowalik, Agnieszka; Lis, Emilia; Tomaszewski, Andrzej; Lach, Tomasz; Boczkowska, Sylwia; Celiński, Krzysztof

2015-01-01

Liver cirrhosis is associated with functional abnormalities of the cardiovascular system with co-existing electrocardiographic (ECG) abnormalities. The aim was to analyze ECG changes in patients with cirrhosis, to evaluate whether alcoholic etiology of cirrhosis and ascites has an impact on ECG changes. The study involved 81 patients with previously untreated alcoholic cirrhosis (64 patients with ascites, classes B and C according to the Child-Pugh classification; and 17 without ascites, categorized as class A); 41 patients with previously untreated cirrhosis due to chronic hepatitis C (HCV--30 patients with ascites, classes B and C; and 11 without ascites, class A); 42 with alcoholic steatohepatitis and 46 with alcoholic steatosis. The control group consisted of 32 healthy volunteers. Twelve-lead ECG recordings were performed and selected parameters were measured. Significantly longer QT and QTc intervals and lower QRS voltage were found in patients with alcoholic and HCV cirrhosis compared to the controls. Significantly lower QRS voltage was found in subjects with ascites than in those without ascites. Removal of ascites significantly increased QRS voltage. In cirrhosis, irrespective of etiology, ECG changes involved prolonged QT and QTc intervals and reduced QRS voltage. Prolonged QT and QTc intervals were not related to the severity of cirrhosis or to the presence of ascites. However, low QRS voltage was associated with the presence of ascites. Removal of ascites reverses low QRS voltage.

Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis.

PubMed

Abe, Hiroshi; Aida, Yuta; Seki, Nobuyoshi; Sugita, Tomonori; Tomita, Yoichi; Nagano, Tomohisa; Itagaki, Munenori; Sutoh, Satoshi; Nagatsuma, Keisuke; Itoh, Kyoko; Matsuura, Tomokazu; Aizawa, Yoshio

2015-09-01

We aimed to clarify the influences of aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) polymorphisms, and ethanol consumption profile to hepatocellular carcinoma (HCC) development in alcoholic liver cirrhosis without chronic hepatitis B and C virus infection (non-B non-C). Of 236 freshly diagnosed non-B non-C alcoholic liver cirrhosis patients, 67 were diagnosed as HCC and the remaining 169 as not having HCC. The relationship between the genetic polymorphisms and development to HCC were evaluated in well-matched patients with HCC (HCC group, n = 67) and without HCC (non-HCC group, n = 67) using propensity scores in age, sex, and prevalence of diabetes mellitus. Daily amount of ethanol consumption was significantly lower (P = 0.005), and consumptive period was significantly longer (P = 0.003) in HCC group than non-HCC group. Of 134 well-matched patients, 113 (84.3%) had ALDH2*1/*1 genotype and 21 (15.7%) had ALDH2*1/*2 genotype. In HCC development, consumptive long period (P = 0.007) and carrying ALDH2*1/*2 genotype (P = 0.026) were identified as significant factors independently participated, while there was no relation to ADH1B polymorphism. In addition, consumptive period was significantly longer in HCC group than non-HCC group in ALDH2*1/*1 genotype patients (P = 0.0005), while there was no difference in profile of ethanol consumption in ALDH2*1/*2 genotype patients. Among HCC group, daily (P = 3.78 × 10(-6) ) and cumulative amount (P = 4.89 × 10(-6) ) of ethanol consumption were significantly higher in ALDH2*1/*1 genotype patients than ALDH2*1/*2 genotype patients. In alcoholic liver cirrhosis, investigations of ALDH2 polymorphism and ethanol consumption profile are useful for prediction of HCC development. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Alcohol-Related Problems and Risk for Suicide among College Students: The Mediating Roles of Belongingness and Burdensomeness

PubMed Central

Lamis, Dorian A.; Malone, Patrick S.

2012-01-01

This study examined the relations among alcohol-related problems, perceived burdensomeness, thwarted belongingness, and suicide proneness in undergraduate college students (N = 996). As hypothesized, alcohol-related problems, perceived burdensomeness, and thwarted belongingness were all significantly and positively correlated with suicide proneness. The relation between experiencing alcohol-related problems and suicide proneness was, in part, accounted for by perceived burdensomeness and thwarted belongingness. Additionally, the mediation via perceived burdensomeness was significantly stronger than the mediation via thwarted belongingness. Results suggest that it would be advisable for clinicians to be aware of students’ experiences with alcohol-related problems in conjunction with their levels of burdensomeness and belongingness when assessing for suicide risk PMID:21883409

Nutritional therapy in cirrhosis or alcoholic hepatitis: a systematic review and meta-analysis.

PubMed

Fialla, Annette D; Israelsen, Mads; Hamberg, Ole; Krag, Aleksander; Gluud, Lise Lotte

2015-09-01

Patients with cirrhosis and alcoholic hepatitis are often malnourished and have a superimposed stress metabolism, which increases nutritional demands. We performed a systematic review on the effects of nutritional therapy vs. no intervention for patients with cirrhosis or alcoholic hepatitis. We included trials on nutritional therapy designed to fulfil at least 75% of daily nutritional demand. Authors extracted data in an independent manner. Random-effects and fixed-effect meta-analyses were performed and the results expressed as risk ratios (RR) with 95% confidence intervals (CI). Sequential analyses were performed to evaluate the risk of spurious findings because of random and systematic errors. Subgroup and sensitivity analyses were performed to evaluate the risk of bias and sources of between trial heterogeneity. Thirteen randomized controlled trials with 329 allocated to enteral (nine trials) or intravenous (four trials) nutrition and 334 controls. All trials were classed as having a high risk of bias. Random-effects meta-analysis showed that nutritional therapy reduced mortality 0.80 (95% CI, 0.64 to 0.99). The result was not confirmed in sequential analysis. Fixed-effect analysis suggested that nutrition prevented overt hepatic encephalopathy (0.73; 95% CI, 0.55 to 0.96) and infection (0.66; 95% CI, 0.45 to 0.98, respectively), but the results were not confirmed in random-effects analyses. Our review suggests that nutritional therapy may have beneficial effects on clinical outcomes in cirrhosis and alcoholic hepatitis. High-quality trials are needed to verify our findings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Social anxiety and alcohol-related negative consequences among college drinkers: do protective behavioral strategies mediate the association?

PubMed

Villarosa, Margo C; Moorer, Kayla D; Madson, Michael B; Zeigler-Hill, Virgil; Noble, Jeremy J

2014-09-01

The link between social anxiety and alcohol-related negative consequences among college students has been well documented. Protective behavioral strategies are cognitive-behavioral strategies that college students use in an effort to reduce harm while they are drinking. In the current study we examined the mediating role of the 2 categories of protective behavioral strategies (i.e., controlled consumption and serious harm reduction) in the relationship that social anxiety symptoms have with alcohol-related negative consequences. Participants were 572 undergraduates who completed measures of social anxiety, alcohol use, negative consequences of alcohol use, and protective behavioral strategy use. Only serious harm reduction strategies emerged as a mediator of the association that social anxiety symptoms had with alcohol-related negative consequences. Clinical and research implications are discussed.

Alcohol-Related Problems in High-Risk Groups. EURO Reports and Studies 109. Report on a WHO Study.

ERIC Educational Resources Information Center

Plant, Martin, Ed.

Alcohol consumption has risen dramatically in many countries since the Second World War. Accompanying this rise has been a rise in alcohol-related problems, including liver cirrhosis mortality, alcohol dependence, and alcohol-related crimes and accidents. Alcohol misuse presents huge health, social, and legal problems throughout most of Europe and…

Friends' Alcohol-Related Social Networking Site Activity Predicts Escalations in Adolescent Drinking: Mediation by Peer Norms.

PubMed

Nesi, Jacqueline; Rothenberg, W Andrew; Hussong, Andrea M; Jackson, Kristina M

2017-06-01

Adolescents' increased use of social networking sites (SNS) coincides with a developmental period of heightened risk for alcohol use initiation. However, little is known regarding associations between adolescents' SNS use and drinking initiation nor the mechanisms of this association. This study examined longitudinal associations among adolescents' exposure to friends' alcohol-related SNS postings, alcohol-favorable peer injunctive norms, and initiation of drinking behaviors. Participants were 658 high-school students who reported on posting of alcohol-related SNS content by self and friends, alcohol-related injunctive norms, and other developmental risk factors for alcohol use at two time points, 1 year apart. Participants also reported on initiation of three drinking behaviors: consuming a full drink, becoming drunk, and heavy episodic drinking (three or more drinks per occasion). Probit regression analyses were used to predict initiation of drinking behaviors from exposure to alcohol-related SNS content. Path analyses examined mediation of this association by peer injunctive norms. Exposure to friends' alcohol-related SNS content predicted adolescents' initiation of drinking and heavy episodic drinking 1 year later, controlling for demographic and known developmental risk factors for alcohol use (i.e., parental monitoring and peer orientation). In addition, alcohol-favorable peer injunctive norms statistically mediated the relationship between alcohol-related SNS exposure and each drinking milestone. Results suggest that social media plays a unique role in contributing to peer influence processes surrounding alcohol use and highlight the need for future investigative and preventive efforts to account for adolescents' changing social environments. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Confluent hepatic fibrosis in liver cirrhosis: possible relation with middle hepatic venous drainage.

PubMed

Ozaki, Kumi; Matsui, Osamu; Gabata, Toshifumi; Kobayashi, Satoshi; Koda, Wataru; Minami, Tetsuya

2013-08-01

Our aim was to retrospectively analyze the location of confluent hepatic fibrosis in relation to the portal and hepatic venous anatomy using multidetector computed tomography (CT) and to clarify the influence of the hepatic venous drainage on confluent fibrosis. The study population consisted of 879 patients diagnosed with cirrhosis: 539 men and 340 women (65.9 ± 10.6 years) and 633 with Child-Pugh class A, 161 with class B, and 85 with class C. The cause of cirrhosis was hepatitis C (n = 528) and hepatitis B (n = 122) virus infection, alcoholism (n = 114), and others (n = 115). The confluent fibrosis was diagnosed using CT images according to previous reports and statistically analyzed (p < 0.05). Thirty-five confluent fibrosis lesions in 30 patients (3.4 %) were identified. The predictive factors were alcoholic cirrhosis [odds ratio (OR), 7.25; p < 0.0001], Child-Pugh class C (OR, 6.95; p < 0.0001), and Child-Pugh class B (OR, 2.91; p < 0.0023). Confluent fibrosis was most frequently seen in the middle hepatic venous drainage area (n = 21) or at the boundary between the medial and anterior segments (n = 17), and each distribution of the location of confluent fibrosis was significantly unequal (p < 0.0001). Confluent fibrosis was most commonly located in the middle hepatic venous drainage area.

Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver.

PubMed

McVicker, Benita L; Thiele, Geoffrey M; Tuma, Dean J; Casey, Carol A

2014-09-01

The consumption of alcohol is associated with many health issues including alcoholic liver disease (ALD). The natural history of ALD involves the development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis. During the stage of steatohepatitis, the combination of inflammation and cellular damage can progress to a severe condition termed alcoholic hepatitis (AH). Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations have been identified in host defense and liver immunity mechanisms during AH that highlight the role of intrahepatic lymphocyte accumulation and associated inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced injury to liver cells may significantly contribute to the aberrant lymphocytic distribution that is seen in AH. In particular, the regulation of lymphocytes by hepatocytes may be disrupted in the alcoholic liver resulting in altered immunologic homeostasis and perpetuation of disease. In recent studies, it was demonstrated that the direct killing of activated T lymphocytes by hepatocytes is facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well-characterized glycoprotein receptor that is exclusively expressed by hepatocytes. This hepatic receptor is known for its role in the clearance of desialylated glycoproteins or cells, yet neither its physiological function nor its role in disease states has been determined. Interestingly, alcohol markedly impairs ASGPR function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of lymphocytes remains to be elucidated. This review discusses the contribution of hepatocytes in immunological regulation and, importantly, how pathological effects of ethanol disrupt hepatocellular-mediated defense mechanisms.

Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol.

PubMed

Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

2015-08-28

To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. It is feasible to establish an animal model of hepatic cirrhosis and

The gender specific mediational pathways between parenting styles, neuroticism, pathological reasons for drinking, and alcohol-related problems in emerging adulthood.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2009-03-01

Mediational links between parenting styles, neuroticism, pathological reasons for drinking, alcohol use and alcohol-related problems were tested. A two-group SEM path model with 441 (216 female, 225 male) college students was examined. In general, pathological reasons for drinking mediated the impact of neuroticism on alcohol use and alcohol-related problems. A different pattern of relationships was found for each of the two genders. Perceptions of having an authoritarian father were positively linked to higher levels of neuroticism among males but this pattern was not found among females. For males, neuroticism mediated the impact of having an authoritarian father on pathological reasons for drinking with pathological reasons for drinking mediating the impact of neuroticism on alcohol-related problems. Perceptions of having a permissive father were linked to lower levels of neuroticism in females (but have been found as a consistent risk factor for other pathways to alcohol use elsewhere). Compared with other work in this area, these findings indicate parental influences regarding vulnerabilities for alcohol use may be specific to parent-child gender matches for some pathways and specific to one parent (irrespective of child gender) for other pathways.

Incidence and Outcomes for Patients With Cirrhosis Admitted to the United Kingdom Critical Care Units.

PubMed

McPhail, Mark J W; Parrott, Francesca; Wendon, Julia A; Harrison, David A; Rowan, Kathy A; Bernal, William

2018-05-01

To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. Retrospective cohort study. Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. None. Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and Chronic Health Evaluation II score for patients with alcohol-related liver disease in 2012 was 20.6 (7.0) and 19.0 (7.2) for non-alcohol-related liver disease (p < 0.001). In adjusted analysis, alcohol-related liver disease was associated with increased risk of death (odds ratio, 1.51 [95% CI, 1.42-1.62; p < 0.001]) with a year-on-year reduction in hospital mortality (adjusted odds ratio, 0.95/yr, [0.94-0.96, p < 0.001]). More patients with cirrhosis are being admitted to critical care units but with increasing survival rates. Patients with alcohol-related liver disease have reduced survival rates partly explained by higher levels of organ failure at admission. Patients with cirrhosis and organ failure warrant a trial of organ support and universal prognostic pessimism is not justified.

Anxiety sensitivity, coping motives, emotion dysregulation, and alcohol-related outcomes in college women: a moderated-mediation model.

PubMed

Chandley, Rachel B; Luebbe, Aaron M; Messman-Moore, Terri L; Ward, Rose Marie

2014-01-01

The present study examined the relation of anxiety sensitivity to alcohol-related outcomes via coping drinking motives in college women. Further, the impact of emotion dysregulation on the mediational path between anxiety sensitivity and alcohol-related outcomes was investigated. A sample of 223 female undergraduate drinkers from a midwestern university completed self-report surveys assessing alcohol consumption, alcohol-related problems, anxiety sensitivity, coping drinking motives, and emotion dysregulation. Anxiety sensitivity was indirectly related to both alcohol-related problems and alcohol use via coping motives. The indirect effect of anxiety sensitivity on alcohol-related problems (but not alcohol use) was qualified by the level of emotion dysregulation. As individuals reported more emotion dysregulation, the strength of the relation between coping drinking motives and alcohol-related problems increased. Results replicate and extend the link between anxiety sensitivity and alcohol outcomes via the mechanism of negative reinforcement, and they further support the importance of emotion dysregulation in explaining alcohol-related problems among college women. Implications for treatment and prevention of alcohol-related problems in college women are discussed.

Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis.

PubMed

Vatansever, Sezgin; Tekin, Fatih; Salman, Esin; Altintoprak, Ender; Coskunol, Hakan; Akarca, Ulus Salih

2015-05-17

No data exists regarding the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) gene polymorphisms in Turkish alcoholic cirrhotics. We studied the polymorphisms of ADH1B, ADH1C and ALDH2 genes in alcoholic cirrhotics and compared the results with non-cirrhotic alcoholics and healthy volunteers. Overall, 237 subjects were included for the study: 156 alcoholic patients (78 cirrhotics, 78 non-cirrhotic alcoholics) and 81 healthy volunteers. Three different single-nucleotide-polymorphism genotyping methods were used. ADH1C genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism method. The identified ADH1C genotypes were named according to the presence or absence of the enzyme restriction sites. ADH1B (Arg47Hys) genotyping was performed using the allele specific primer extension method, and ALDH2 (Glu487Lys) genotyping was performed by a multiplex polymerase chain reaction using two allele-specific primer pairs. For ADH1B, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 97.4%, 94.9% and 99.4%, respectively. For ADH1C, the frequency of allele *1 in the cirrhotics, non-cirrhotic alcoholics and healthy volunteers was 47%, 36.3% and 45%, respectively. There was no statistical difference between the groups for ADH1B and ADH1C (p>0.05). All alcoholic and non-alcoholic subjects (100%) had the allele *1 for ALDH2. The obtained results for ADH1B, ADH1C, and ALDH gene polymorphisms in the present study are similar to the results of Caucasian studies. ADH1B and ADH1C genetic variations are not related to the development of alcoholism or susceptibility to alcoholic cirrhosis. ALDH2 gene has no genetic variation in the Turkish population.

Distinctive aspects of peptic ulcer disease, Dieulafoy's lesion, and Mallory-Weiss syndrome in patients with advanced alcoholic liver disease or cirrhosis

PubMed Central

Nojkov, Borko; Cappell, Mitchell S

2016-01-01

AIM: To systematically review the data on distinctive aspects of peptic ulcer disease (PUD), Dieulafoy’s lesion (DL), and Mallory-Weiss syndrome (MWS) in patients with advanced alcoholic liver disease (aALD), including alcoholic hepatitis or alcoholic cirrhosis. METHODS: Computerized literature search performed via PubMed using the following medical subject heading terms and keywords: “alcoholic liver disease”, “alcoholic hepatitis”,“ alcoholic cirrhosis”, “cirrhosis”, “liver disease”, “upper gastrointestinal bleeding”, “non-variceal upper gastrointestinal bleeding”, “PUD”, ‘‘DL’’, ‘‘Mallory-Weiss tear”, and “MWS’’. RESULTS: While the majority of acute gastrointestinal (GI) bleeding with aALD is related to portal hypertension, about 30%-40% of acute GI bleeding in patients with aALD is unrelated to portal hypertension. Such bleeding constitutes an important complication of aALD because of its frequency, severity, and associated mortality. Patients with cirrhosis have a markedly increased risk of PUD, which further increases with the progression of cirrhosis. Patients with cirrhosis or aALD and peptic ulcer bleeding (PUB) have worse clinical outcomes than other patients with PUB, including uncontrolled bleeding, rebleeding, and mortality. Alcohol consumption, nonsteroidal anti-inflammatory drug use, and portal hypertension may have a pathogenic role in the development of PUD in patients with aALD. Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients. The frequency of bleeding from DL appears to be increased in patients with aALD. DL may be associated with an especially high mortality in these patients. MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism, and is associated with aALD. Patients with aALD have more severe MWS bleeding and are more likely to rebleed when compared to non

Association between Serum Selenium Concentrations and Levels of Proinflammatory and Profibrotic Cytokines-Interleukin-6 and Growth Differentiation Factor-15, in Patients with Alcoholic Liver Cirrhosis.

PubMed

Prystupa, Andrzej; Kiciński, Paweł; Luchowska-Kocot, Dorota; Błażewicz, Anna; Niedziałek, Jarosław; Mizerski, Grzegorz; Jojczuk, Mariusz; Ochal, Andrzej; Sak, Jarosław J; Załuska, Wojciech

2017-04-21

According to some authors, serum selenium levels are strongly associated with the severity of liver diseases, including liver cirrhosis. The aim of this study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines-interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in the serum of 99 patients with alcoholic liver cirrhosis divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower, whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.

Long-term change in incidence and risk factors of cirrhosis and hepatocellular carcinoma in Crete, Greece: a 25-year study.

PubMed

Karageorgos, Spyridon A; Stratakou, Soultana; Koulentaki, Mairi; Voumvouraki, Argyro; Mantaka, Aikaterini; Samonakis, Dimitrios; Notas, George; Kouroumalis, Elias A

2017-01-01

No sequential long-term data exist for Greece on the etiological evolution and incidence of cirrhosis and hepatocellular carcinoma. Therefore, we studied their etiological evolution over a period of 25 years in the island of Crete. We studied 812 cases of cirrhosis (561 male, median age 69 years) and 321 cases of hepatocellular carcinoma (234 male, median age 70 years) from the database of our Center. Cases were classified into five-year periods according to incidence and etiology (hepatitis B, hepatitis C, alcohol, alcohol plus viral, and non-alcoholic fatty liver disease). Overall, there was an increase in the incidence of hepatocellular carcinoma. A significant fourfold reduction in the incidence of hepatitis C-related cirrhosis was observed, which was degraded from first to third place as a risk factor for cirrhosis. Alcohol gradually became the first risk factor in cirrhosis (1990-94: 36.1%, 2010-14: 52.3%) and carcinoma, while the steepest increase in incidence of cirrhosis and carcinoma was associated with non-alcoholic fatty liver disease. The incidence of cirrhosis remained constant over the years, but the incidence of hepatocellular carcinoma increased during the last decade. Risk factors for cirrhosis and hepatocellular carcinoma have changed over the past 25 years in Crete. The initial high hepatitis C virus association has significantly decreased, with alcohol now ranking first among risk factors. Non-alcoholic fatty liver disease is continually increasing and is a prominent risk factor for cirrhosis and hepatocellular carcinoma.

Agreeableness and alcohol-related aggression: the mediating effect of trait aggressivity.

PubMed

Miller, Cameron A; Parrott, Dominic J; Giancola, Peter R

2009-12-01

This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality.

Fibromyalgia Symptoms and Cirrhosis

PubMed Central

Bielefeldt, Klaus; Wasan, Ajay D.; Szigethy, Eva; Lotrich, Francis; DiMartini, Andrea F.

2015-01-01

Background An association between fibromyalgia and hepatitis C virus (HCV) has been previously described. However, the relationship between nonalcoholic steatohepatitis (NASH) and fibromyalgia symptoms has not been assessed, though they share several risk factors. Aim We aimed to assess the factors associated with fibromyalgia symptoms across etiologies of liver disease. Methods Patients with cirrhosis due to HCV, NASH, or alcohol were recruited from an outpatient hepatology clinic and administered the Hospital Anxiety and Depression Score, Pittsburgh Sleep Quality Index, and the modified 2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia. Serum inflammatory markers were measured with standard luminex assays. Results Of 193 participants, 53 (27 %) met criteria for fibromyalgia. Fibromyalgia symptoms were significantly associated with etiology of liver disease (HCV: 35 %, NASH: 30 %, alcohol-related liver disease: 12 %, p < 0.01). Using logistic regression, mood symptoms (OR 1.14, 95 % CI 1.06, 1.22), sleep disturbance (OR 1.32, 95 % CI 1.16, 1.52), and etiology of liver disease (NASH vs. HCV not different, alcohol vs. HCV OR 0.19, 95 % CI 0.05, 0.63) were associated with fibromyalgia symptoms. If abdominal pain was included in the model, etiology became nonsignificant, indicating that it may be central sensitization due to abdominal pain in patients with chronic liver disease that explains fibromyalgia symptoms rather than the etiology of liver disease or inflammation. Conclusions Fibromyalgia symptoms were significantly associated with HCV and NASH cirrhosis and with psychiatric symptoms. Future work should focus on the underlying pathophysiology and management of widespread pain in patients with cirrhosis. PMID:25433921

Helicobacter pylori infection among patients with liver cirrhosis.

PubMed

Pogorzelska, Joanna; Łapińska, Magda; Kalinowska, Alicja; Łapiński, Tadeusz W; Flisiak, Robert

2017-10-01

Inflammatory changes in the stomach caused by Helicobacter pylori indirectly and directly affect liver function. Moreover, the bacteria may worsen the course of the liver cirrhosis. The study aimed at evaluating the incidence of H. pylori infection among patients with liver cirrhosis, depending on the etiology and injury stage, scored according to Child-Pugh classification. Stage of esophageal varices and endoscopic inflammatory lesions in the stomach were evaluated, depending on the presence of H. pylori infection. The study included 147 patients with liver cirrhosis: 42 were infected with hepatitis C virus, 31 were infected with hepatitis B virus, 56 had alcoholic liver cirrhosis, and 18 had primary biliary cirrhosis. Diagnosis of H. pylori infection was performed based on the presence of immunoglobulin G antibodies in serum. H. pylori infection was found in 46.9% of patients. The incidence of H. pylori infection among patients with postinflammatory liver cirrhosis was significantly higher (P=0.001), as compared with patients with alcoholic liver cirrhosis. Ammonia concentration was significantly higher in patients infected with H. pylori, compared with noninfected individuals (129 vs. 112 μmol/l; P=0.002). Incidence of H. pylori infection in patients without esophageal varices was significantly lower compared with patients with esophageal varices (14 vs. 60%; P<0.001). H. pylori infection is significantly more frequent among patients with postinflammatory liver cirrhosis (infected with hepatitis C virus or hepatitis B virus) than in patients with alcoholic liver cirrhosis or primary biliary cirrhosis. H. pylori infection correlates with elevated concentration of blood ammonia and the incidence of esophageal varices.

Non-invasive prediction of forthcoming cirrhosis-related complications

PubMed Central

Kang, Wonseok; Kim, Seung Up; Ahn, Sang Hoon

2014-01-01

In patients with chronic liver diseases, identification of significant liver fibrosis and cirrhosis is essential for determining treatment strategies, assessing therapeutic response, and stratifying long-term prognosis. Although liver biopsy remains the reference standard for evaluating the extent of liver fibrosis in patients with chronic liver diseases, several non-invasive methods have been developed as alternatives to liver biopsies. Some of these non-invasive methods have demonstrated clinical accuracy for diagnosing significant fibrosis or cirrhosis in many cross-sectional studies with the histological fibrosis stage as a reference standard. However, non-invasive methods cannot be fully validated through cross-sectional studies since liver biopsy is not a perfect surrogate endpoint marker. Accordingly, recent studies have focused on assessing the performance of non-invasive methods through long-term, longitudinal, follow-up studies with solid clinical endpoints related to advanced stages of liver fibrosis and cirrhosis. As a result, current view is that these alternative methods can independently predict future cirrhosis-related complications, such as hepatic decompensation, liver failure, hepatocellular carcinoma, or liver-related death. The clinical role of non-invasive models seems to be shifting from a simple tool for predicting the extent of fibrosis to a surveillance tool for predicting future liver-related events. In this article, we will summarize recent longitudinal studies of non-invasive methods for predicting forthcoming complications related to liver cirrhosis and discuss the clinical value of currently available non-invasive methods based on evidence from the literature. PMID:24627597

Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease.

PubMed

Dubinkina, Veronika B; Tyakht, Alexander V; Odintsova, Vera Y; Yarygin, Konstantin S; Kovarsky, Boris A; Pavlenko, Alexander V; Ischenko, Dmitry S; Popenko, Anna S; Alexeev, Dmitry G; Taraskina, Anastasiya Y; Nasyrova, Regina F; Krupitsky, Evgeny M; Shalikiani, Nino V; Bakulin, Igor G; Shcherbakov, Petr L; Skorodumova, Lyubov O; Larin, Andrei K; Kostryukova, Elena S; Abdulkhakov, Rustam A; Abdulkhakov, Sayar R; Malanin, Sergey Y; Ismagilova, Ruzilya K; Grigoryeva, Tatiana V; Ilina, Elena N; Govorun, Vadim M

2017-10-17

Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative "shotgun" metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts-with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group. Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis-with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus-but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of

Characteristics of liver cirrhosis in Italy: Evidence for a decreasing role of HCV aetiology.

PubMed

Stroffolini, Tommaso; Sagnelli, Evangelista; Gaeta, Giovanni Battista; Sagnelli, Caterina; Andriulli, Angelo; Brancaccio, Giuseppina; Pirisi, Mario; Colloredo, Guido; Morisco, Filomena; Furlan, Caterina; Almasio, Piero Luigi

2017-03-01

Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p=0.02). Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p<0.05) decreasing role of both HCV infection and alcohol abuse as aetiologic agents of liver cirrhosis in Italy, explaining, at least in part, the slow, progressive decline of the mortality rate for liver cirrhosis in the last decades in this country (from 34.5 deaths/100,000 inhabitants in1980 to 10.8 in 2012). Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis.

PubMed

Falleti, Edmondo; Cussigh, Annarosa; Cmet, Sara; Fabris, Carlo; Toniutto, Pierluigi

2016-01-01

PNPLA3 rs738409 polymorphism is associated with fatty liver disease, alcoholic or non-alcoholic (NAFLD) and hepatocellular carcinoma (HCC). TM6SF2 rs58542926 is clearly associated with NAFLD, but it is not clearly associated with HCC. The relationship between TM6SF2 rs58542926 and HCC and the potential synergistic effect of TM6SF2 and PNPLA3 variants in modifying the risk of HCC are not known. This study assessed the interaction between PNPLA3 rs738409 and TM6SF2 rs58542926 variants in the conditioning of HCC development. A total of 511 cirrhotic patients (44% alcohol-related, 56% viral, 57.5% liver transplanted) were retrospectively investigated for HCC occurrence. PNPLA3 rs734809 and TM6SF2 rs58542926 were genotyped using restriction fragment length polymorphism and real-time allelic discrimination polymerase chain reaction methods. Patients with HCC were more likely to be PNPLA3 rs734809 G/G homozygotes (41/150 vs. 60/361, p=0.009) or TM6SF2 rs58542926 C/T-T/T (27/150 vs. 41/361, p=0.044). The presence of either PNPLA3 G/G or TM6SF2*/T identified high-risk genotypes for HCC, which were strongly associated with HCC (64/150 vs. 93/361, p=0.0002). This association was evident in alcohol-related (p=0.0007) but not in viral cirrhosis. TM6SF2 C/T or T/T in conjunction with PNPLA3 G/G variants may be potential genetic risk factors for developing HCC in alcohol-related cirrhosis. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Wartime Paris, cirrhosis mortality, and the ceteris paribus assumption.

PubMed

Fillmore, Kaye Middleton; Roizen, Ron; Farrell, Michael; Kerr, William; Lemmens, Paul

2002-07-01

This article critiques the ceteris paribus assumption, which tacitly sustains the epidemiologic literature's inference that the sharp decline in cirrhosis mortality observed in Paris during the Second World War derived from a sharp constriction in wine consumption. Paris's wartime circumstances deviate substantially from the "all else being equal" assumption, and at least three other hypotheses for the cirrhosis decline may be contemplated. Historical and statistical review. Wartime Paris underwent tumultuous changes. Wine consumption did decline, but there were, as well, a myriad of other changes in diet and life experience, many involving new or heightened hardships, nutritional, experiential, institutional, health and mortality risks. Three competing hypotheses are presented: (1) A fraction of the candidates for cirrhosis mortality may have fallen to more sudden forms of death; (2) alcoholics, heavy drinkers and Paris's clochard subpopulation may have been differentially likely to become removed from the city's wartime population, whether by self-initiated departure, arrest and deportation, or death from other causes, even murder; and (3) there was mismeasurement in the cirrhosis mortality decline. The alcohol-cirrhosis connection provided the template for the alcohol research effort (now more than 20 years old) aimed at re-establishing scientific recognition of alcohol's direct alcohol-problems-generating associations and causal responsibilities. In a time given to reports of weaker associations of the alcohol-cirrhosis connection, the place and importance of the Paris curve in the wider literature, as regards that connection, remains. For this reason, the Paris findings should be subjected to as much research scrutiny as they undoubtedly deserve.

Gender-specific mediational links between parenting styles, parental monitoring, impulsiveness, drinking control, and alcohol-related problems.

PubMed

Patock-Peckham, Julie A; King, Kevin M; Morgan-Lopez, Antonio A; Ulloa, Emilio C; Moses, Jennifer M Filson

2011-03-01

Recently, it has been suggested that traits may dynamically change as conditions change. One possible mechanism that may influence impulsiveness is parental monitoring. Parental monitoring reflects a knowledge regarding one's offspring's whereabouts and social connections. The aim of this investigation was to examine potential gender-specific parental influences to impulsiveness (general behavioral control), control over one's own drinking (specific behavioral control), and alcohol-related problems among individuals in a period of emerging adulthood. Direct and mediational links between parenting styles (permissive, authoritarian, and authoritative), parental monitoring, impulsiveness, drinking control, and alcohol-related problems were investigated. A multiple-group, SEM model with (316 women, 265 men) university students was examined. In general, the overall pattern among male and female respondents was distinct. For daughters, perceptions of a permissive father were indirectly linked to more alcohol-related problems through lower levels of monitoring by fathers and more impulsive symptoms. Perceptions of an authoritative father were also indirectly linked to fewer impulsive symptoms through higher levels of monitoring by fathers among daughters. For men, perceptions of a permissive mother were indirectly linked to more alcohol-related problems through lower levels of monitoring by mothers and more impulsive symptoms. For sons, perceptions of mother authoritativeness were indirectly linked to fewer alcohol-related problems through more monitoring by mothers and fewer impulsive symptoms. Monitoring by an opposite-gender parent mediated the link between parenting styles (i.e., permissive, authoritative) on impulsiveness.

College drinking behaviors: mediational links between parenting styles, impulse control, and alcohol-related outcomes.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2006-06-01

Mediational links between parenting styles (authoritative, authoritarian, permissive), impulsiveness (general control), drinking control (specific control), and alcohol use and abuse were tested. A pattern-mixture approach (for modeling non-ignorable missing data) with multiple-group structural equation models with 421 (206 female, 215 male) college students was used. Gender was examined as a potential moderator of parenting styles on control processes related to drinking. Specifically, the parent-child gender match was found to have implications for increased levels of impulsiveness (a significant mediator of parenting effects on drinking control). These findings suggest that a parent with a permissive parenting style who is the same gender as the respondent can directly influence control processes and indirectly influence alcohol use and abuse.

Mediational Links Among Parenting Styles, Perceptions of Parental Confidence, Self-Esteem, and Depression on Alcohol-Related Problems in Emerging Adulthood*

PubMed Central

Patock-Peckham, Julie A.; Morgan-Lopez, Antonio A.

2009-01-01

Objective: Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Method: Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Results: Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. Conclusions: The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems. PMID:19261233

Mediational links among parenting styles, perceptions of parental confidence, self-esteem, and depression on alcohol-related problems in emerging adulthood.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2009-03-01

Depression is often found to be comorbid with alcohol-related problems. Parental overprotection, which may be of particular importance during emerging adulthood, has been linked to internalizing symptoms in offspring. This article evaluates the impact of parenting styles and parental confidence in their offspring on an internalizing pathway to alcohol-related problems through self-esteem and depression. Mediational links were tested among parenting styles (authoritative, authoritarian, permissive), parental confidence (overprotection, autonomy), self-esteem, depression, and alcohol-related problems. A two-group, multiple indicator multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. Overall, having a father who was confident in his child's ability to make autonomous decisions was protective against depression for both genders. Perceptions of paternal autonomy mediated the impact of the fathers' parenting styles (authoritative, permissive) on depression for both genders. For men, parental overprotection mediated the impact of an authoritarian father on self-esteem, and self-esteem mediated the impact of parental overprotection on depression. Moreover, among men, perceptions of maternal autonomy mediated the impact of the mothers' parenting styles (authoritative, permissive) on self-esteem, and self-esteem mediated the impact of maternal autonomy on depression. The current pattern of findings is distinct from pathways through behavioral undercontrol with influences from the same-sex parent for both genders. These findings indicate that parenting may have differential influences on internalizing pathways to alcohol-related problems.

Alcohol and liver cirrhosis mortality in the United States: comparison of methods for the analyses of time-series panel data models.

PubMed

Ye, Yu; Kerr, William C

2011-01-01

To explore various model specifications in estimating relationships between liver cirrhosis mortality rates and per capita alcohol consumption in aggregate-level cross-section time-series data. Using a series of liver cirrhosis mortality rates from 1950 to 2002 for 47 U.S. states, the effects of alcohol consumption were estimated from pooled autoregressive integrated moving average (ARIMA) models and 4 types of panel data models: generalized estimating equation, generalized least square, fixed effect, and multilevel models. Various specifications of error term structure under each type of model were also examined. Different approaches controlling for time trends and for using concurrent or accumulated consumption as predictors were also evaluated. When cirrhosis mortality was predicted by total alcohol, highly consistent estimates were found between ARIMA and panel data analyses, with an average overall effect of 0.07 to 0.09. Less consistent estimates were derived using spirits, beer, and wine consumption as predictors. When multiple geographic time series are combined as panel data, none of existent models could accommodate all sources of heterogeneity such that any type of panel model must employ some form of generalization. Different types of panel data models should thus be estimated to examine the robustness of findings. We also suggest cautious interpretation when beverage-specific volumes are used as predictors. Copyright © 2010 by the Research Society on Alcoholism.

Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.

PubMed

Kelly, John F; Hoeppner, Bettina; Stout, Robert L; Pagano, Maria

2012-02-01

Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Nine clinical sites within the United States. Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population.

PubMed

D'Amico, Mario; Pasta, Francesca; Pasta, Linda

2015-08-15

The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian patients with liver cirrhosis, consecutively enrolled from June 2008 to January 2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT were the most frequent THRGFs, statistically significant in patients with alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28, 50 and 73, and 65 and 83 (all chi-square tests>3.84, and p values<0.05). Two logistic regression analysis, using PAI-1 4G-4G and MTHFR 677TT, as dependent variable, confirmed the independent significant relationship of these THRGFs with alcohol, cryptogenic liver cirrhosis and PVT. PAI 1 and MTHFR 677 genotypes, deviated from those expected in populations in Hardy-Weinberg equilibrium (all p values<0.05), in the subgroups of patients with alcohol, cryptogenic liver cirrhosis and presence of PVT. Our study shows the pivotal role of PAI-1 4G-4G and MTHFR 677TT in patients with alcohol, cryptogenic liver cirrhosis, and PVT, in a Caucasian population. In conclusion, thrombo and fibro-genetic mechanisms of PAI-1 4G-4G and MTHFR 677TT, could have a role in the development of liver cirrhosis, mainly in patients without HCV and HBV, and PVT. Copyright © 2015 Elsevier B.V. All rights reserved.

Teens’ Attention to Crime and Emergency Programs on Television as a Predictor and Mediator of Increased Risk Perceptions Regarding Alcohol-Related Injuries

PubMed Central

Slater, Michael D.; Jain, Parul

2011-01-01

This study examined the hypotheses that media exposure and attention would predict, and partially mediate, the effects of various individual-difference variables on alcohol-related risk perceptions among teen viewers of crime and emergency (e.g. medical drama) shows on television. Risk perceptions including perceived severity, perceived alcohol-attributable fraction of incidents involving alcohol, controllability, and concern regarding alcohol-related crime, assaults, and other injuries were the outcome measures. Attention to crime and emergency shows was predictive of increased concern and other risk perceptions regarding alcohol-related incidents. Attention also partially mediated the effects of demographic and other individual difference variables on adolescents’ risk perceptions regarding alcohol-related injuries. The findings a) suggest emergency and medical drama television narratives can at times have incidental positive impacts on health-related attitudes and b) provide further evidence regarding the endogenous nature of media use variables in influencing such attitudes. PMID:21240701

Teens' attention to crime and emergency programs on television as a predictor and mediator of increased risk perceptions regarding alcohol-related injuries.

PubMed

Slater, Michael D; Jain, Parul

2011-01-01

This study examined the hypotheses that media exposure and attention would predict, and partially mediate, the effects of various individual-difference variables on alcohol-related risk perceptions among teen viewers of crime and emergency (e.g., medical drama) shows on television. Risk perceptions including perceived severity, perceived alcohol-attributable fraction of incidents involving alcohol, controllability, and concern regarding alcohol-related crime, assaults, and other injuries were the outcome measures. Attention to crime and emergency shows was predictive of increased concern and other risk perceptions regarding alcohol-related incidents. Attention also partially mediated the effects of demographic and other individual difference variables on adolescents' risk perceptions regarding alcohol-related injuries. The findings (a) suggest emergency and medical drama television narratives can at times have incidental positive impacts on health-related attitudes and (b) provide further evidence regarding the endogenous nature of media use variables in influencing such attitudes.

College Men and Alcohol Use: Positive Alcohol Expectancies as a Mediator Between Distinct Masculine Norms and Alcohol Use

PubMed Central

Iwamoto, Derek Kenji; Corbin, William; Lejuez, Carl; MacPherson, Laura

2015-01-01

College men are more likely to engage in health-compromising behaviors including risky drinking behavior, and experience more alcohol-related problems, including violence and arrest, as compared to women. The study of masculine norms or societal expectations, defined as beliefs and values about what it means to be a man, is one promising area of investigation that may help explain within-group differences and differential rates of alcohol use among men. Using the gender social learning model, we investigated the role of positive alcohol expectancies as an underlying mediator between masculine norms and alcohol use among college men. Data from 804 college adult men (Mean age = 20.43) were collected through a web-based assessment. Participants completed a self-report measure of binge drinking, frequency of drinking, quantity of drinks, conformity to masculine norms, and positive alcohol expectancies measures. Structural equation modeling was used to examine relations between masculine norms, alcohol expectancies and alcohol use. The masculine norms of “Playboy” and Risk-Taking were positively related to heavy alcohol use, while Emotional Control and Heterosexual Presentation were both negatively associated with alcohol use, after controlling for fraternity Greek status and positive expectancies. Playboy and Winning norms were positively associated with positive expectancies while Power Over Women was inversely related to positive expectancies which, in turn, were associated with heavier alcohol use. This study was a novel exploration into the multiple pathways and mediators through which positive alcohol expectancies may help explain and provide specificity to the masculinity and alcohol use relationship among college men. PMID:25705133

College Men and Alcohol Use: Positive Alcohol Expectancies as a Mediator Between Distinct Masculine Norms and Alcohol Use.

PubMed

Iwamoto, Derek Kenji; Corbin, William; Lejuez, Carl; MacPherson, Laura

2014-01-01

College men are more likely to engage in health-compromising behaviors including risky drinking behavior, and experience more alcohol-related problems, including violence and arrest, as compared to women. The study of masculine norms or societal expectations, defined as beliefs and values about what it means to be a man, is one promising area of investigation that may help explain within-group differences and differential rates of alcohol use among men. Using the gender social learning model, we investigated the role of positive alcohol expectancies as an underlying mediator between masculine norms and alcohol use among college men. Data from 804 college adult men ( Mean age = 20.43) were collected through a web-based assessment. Participants completed a self-report measure of binge drinking, frequency of drinking, quantity of drinks, conformity to masculine norms, and positive alcohol expectancies measures. Structural equation modeling was used to examine relations between masculine norms, alcohol expectancies and alcohol use. The masculine norms of "Playboy" and Risk-Taking were positively related to heavy alcohol use, while Emotional Control and Heterosexual Presentation were both negatively associated with alcohol use, after controlling for fraternity Greek status and positive expectancies. Playboy and Winning norms were positively associated with positive expectancies while Power Over Women was inversely related to positive expectancies which, in turn, were associated with heavier alcohol use. This study was a novel exploration into the multiple pathways and mediators through which positive alcohol expectancies may help explain and provide specificity to the masculinity and alcohol use relationship among college men.

Do alcohol expectancy outcomes and valuations mediate peer influences and lifetime alcohol use among early adolescents?

PubMed

Zamboanga, Byron L; Schwartz, Seth J; Ham, Lindsay S; Jarvis, Lorna Hernandez; Olthuis, Janine V

2009-12-01

Building on the theory of reasoned action (I. Ajzen & M. Fishbein, 1973, 1980; M. Fishbein & I. Ajzen, 1975) and expectancy theory, the authors examined the mediating role of alcohol expectancies in adolescent drinking behaviors by testing whether alcohol expectancy outcomes and valuations (the extent to which these outcomes are perceived as good or bad) mediate the association between peer influences and lifetime alcohol use. Early adolescents (N = 904) from 2 public middle schools in western Michigan completed a battery of questionnaires. Overall, results showed that alcohol expectancies and valuations partially mediated the relations between peer influences (peer use and peer approval) and lifetime alcohol use. The findings suggest that associating with peers who are perceived as using alcohol and approving of drinking may influence adolescents' alcohol expectancies. The authors briefly discuss future research directions and implications for prevention.

Mental Health, not Social Support, Mediates the Forgiveness–Alcohol Outcome Relationship

PubMed Central

Webb, Jon R.; Robinson, Elizabeth A. R.; Brower, Jon R.

2011-01-01

Religiousness and spirituality are important to most Americans and evidence suggests that they may contribute to both addiction and recovery. Forgiveness is a specific dimension of religiousness and spirituality that may enhance recovery, but the mechanism(s) through which it operates is unknown. We hypothesized that higher levels of forgiveness would be associated with higher levels of mental health and social support, which in turn would be associated with improved alcohol-related outcomes. Baseline and 6-month longitudinal data from a sample of 149 individuals with alcohol use disorders seeking outpatient substance abuse treatment were analyzed through multiple-mediation statistical techniques. While previous research has shown direct associations among forgiveness, alcohol-related outcomes, mental health, and social support, this study found that the direct associations between forgiveness and alcohol-related outcomes were no longer significant when mental health and social support were analyzed as mediator variables. At baseline, for each alcohol-related outcome measured (alcohol-related problems, percent heavy drinking days, percent days abstinent, and drinks per drinking day), mental health individually played a role in the relationship with both forgiveness of self and forgiveness of others; fully mediating or operating through an indirect only pathway. For alcohol-related problems only, mental health fully mediated the relationship with forgiveness of self at follow-up and operated through an indirect only pathway with forgiveness of others longitudinally. Social support and feeling forgiven by God were non-significant variables at baseline, follow-up, and longitudinally. PMID:21443306

Alcohol-specific parenting, adolescents' self-control, and alcohol use: a moderated mediation model.

PubMed

Koning, Ina M; van den Eijnden, Regina J J M; Vollebergh, Wilma A M

2014-01-01

There is convincing evidence that parental rules about alcohol are important in curbing adolescents' alcohol use. However, little is known about the mechanisms through which the direct link between alcohol-specific parenting and alcohol use is obtained. In this study, we investigated the mediating effect of adolescent self-control on the relationship between alcohol-specific rules and adolescents' drinking behavior and whether this mediation effect depends on the level of quality of communication. A total of 883 adolescents participated in this longitudinal study at ages 13, 14, and 15 years. Strict rules predicted lower rates of drinking, but no direct effect of the quality of communication on adolescents' alcohol use was found. A higher level of self-control was related to lower rates of drinking in adolescents. The indirect effect of rules about alcohol through adolescents' self-control was statistically significant, yet only in adolescents with high qualitative parent-child communication about alcohol. In adolescents with low quality of parent-child communication, self-control was not related to drinking. These findings imply that strict rule setting in combination with qualitative parent-child communication is an important target for prevention. In addition, findings point at the importance of high qualitative parent-child communication for adolescents' motivation to engage in self-control to avoid drinking.

Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma.

PubMed

Nahon, Pierre; Nault, Jean-Charles

2017-11-01

Exploration of the constitutional genetics of hepatocellular carcinoma (HCC) has identified numerous variants associated with a higher risk of liver cancer in alcoholic cirrhotic patients. Although Genome-Wide Association studies have not been carried out in the field of alcohol-related HCC, common single nucleotide polymorphisms conferring a small increase in the risk of liver cancer risk have been identified and shown to modulate ethanol metabolism, inflammation, oxidative stress, iron or lipid metabolism. Specific patterns of gene mutations including CTNNB1, TERT, ARID1A and SMARCA2 exist in alcohol-related HCC. Moreover, a specific mutational process observed at the nucleotide level by next generation sequencing has revealed cooperation between alcohol and tobacco in the development of HCC. Combining this genetic information with epidemiological and clinical data that might define specific HCC risk classes and refine surveillance strategies needs to be assessed in large prospective cohorts of patients with alcoholic cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Protective behavioral strategies as a mediator and moderator of the relationship between self-regulation and alcohol-related consequences in first-year college students.

PubMed

D'Lima, Gabrielle Maria; Pearson, Matthew R; Kelley, Michelle L

2012-06-01

This study examined protective behavioral strategies (PBS) as a potential mediator and moderator of the relationship between self-regulation and alcohol-related consequences. Participants were 249 first-year undergraduate men and women. The use of PBS partially mediated the relationship between self-regulation and alcohol-related problems (i.e., supporting the "self-control equals drinking control" hypothesis). However, use of PBS appeared more important for those with poorer self-regulation abilities (supporting the "PBS protect the impaired" hypothesis). Because both mediation and moderation were supported, a moderated mediation model was tested. The moderated mediation model demonstrated that the negative relationship between self-regulation and alcohol-related consequences could be explained by use of PBS for individuals with poor-to-average self-regulation but not for individuals with above-average, self-regulation abilities. Implications of the study's findings are discussed.

Impact of physical and psychological factors on health-related quality of life in adult patients with liver cirrhosis: a systematic review protocol.

PubMed

Polis, Suzanne; Fernandez, Ritin

2015-01-01

What is the impact of physical and psychological factors on health-related quality of life in adult patients diagnosed with liver cirrhosis? All chronic liver diseases stimulate a degree of repetitive hepatocyte injury that alters the normal liver architecture and ends in cirrhosis.Liver cirrhosis and hepatocellular carcinoma secondary to livercirrhosis are a major public health burden, reporting increasing mortality and morbidity both in Australia and globally.The four leading causes of cirrhosis include harmful alcohol consumption, viral hepatitis B and C and metabolic syndromes related to non-alcoholic fatty liver disease and obesity.A cirrhotic liver is characterized by the presence of regenerative nodules surrounded by fibrous bands that inhibit the passing of molecules between blood and functional units of liver hepatocytes, leading to liver dysfunction.Additionally, the presence of fibrous bands disrupts the normal vascular architecture, increasing resistance within the liver sinusoids and contributing to increased portal vein pressure.The early stages of cirrhosis are referred to as compensated liver disease with no reported symptoms or evidence of impaired liver function.However, the signs and symptoms of liver failure, as well as the mortality rate, increase as the severity of cirrhosis increases.Transition from compensated to decompensated cirrhosis is marked by one or more physiological changes. The physiological changes include increased portal vein pressure, impaired synthetic function, electrolyte imbalance and malnourishment.These physiological changes trigger the development of physical signs and symptoms and impact on the psychological wellbeing of the individual living with cirrhosis. The physical signs and symptoms include esophageal varices, ascites, hepatic encephalopathy, jaundice, irregular sleep patterns, muscle cramps, pruritus, fatigue, impaired mobility, breathlessness, abdominal discomfort, gastrointestinal symptoms, change of body

Gut microbiota and host metabolism in liver cirrhosis

PubMed Central

Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

2015-01-01

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

Gut microbiota and host metabolism in liver cirrhosis.

PubMed

Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

2015-11-07

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

Mental health, not social support, mediates the forgiveness-alcohol outcome relationship.

PubMed

Webb, Jon R; Robinson, Elizabeth A R; Brower, Kirk J

2011-09-01

Religiousness and spirituality are important to most Americans, and evidence suggests that they may contribute to both addiction and recovery. Forgiveness is a specific dimension of religiousness and spirituality that may enhance recovery, but the mechanism(s) through which it operates is unknown. We hypothesized that higher levels of forgiveness would be associated with higher levels of mental health and social support, which, in turn, would be associated with improved alcohol-related outcomes. Baseline and 6-month longitudinal data from a sample of 149 individuals with alcohol use disorders seeking outpatient substance abuse treatment were analyzed through multiple-mediation statistical techniques. While previous research has shown direct associations among forgiveness, alcohol-related outcomes, mental health, and social support, this study found that the direct associations between forgiveness and alcohol-related outcomes were no longer significant when mental health and social support were analyzed as mediator variables. At baseline, for each alcohol-related outcome measured (alcohol-related problems, percent heavy drinking days, percent days abstinent, and drinks per drinking day), mental health individually played a role in the relationship with both forgiveness of self and forgiveness of others, fully mediating or operating through an indirect-only pathway. For alcohol-related problems only, mental health fully mediated the relationship with forgiveness of self at follow-up and operated through an indirect-only pathway with forgiveness of others longitudinally. Social support and feeling forgiven by God were nonsignificant variables at baseline, follow-up, and longitudinally. (c) 2011 APA, all rights reserved.

Watching and drinking: expectancies, prototypes, and friends' alcohol use mediate the effect of exposure to alcohol use in movies on adolescent drinking.

PubMed

Dal Cin, Sonya; Worth, Keilah A; Gerrard, Meg; Stoolmiller, Mike; Sargent, James D; Wills, Thomas A; Gibbons, Frederick X

2009-07-01

To investigate the psychological processes that underlie the relation between exposure to alcohol use in media and adolescent alcohol use. The design consisted of a structural equation modeling analysis of data from four waves of a longitudinal, nationally representative, random-digit dial telephone survey of adolescents in the United States. The main outcome measures were adolescent alcohol consumption and willingness to use alcohol. Tested mediators were alcohol-related norms, prototypes, expectancies, and friends' use. Alcohol prototypes, expectancies, willingness, and friends' use of alcohol (but not perceived prevalence of alcohol use among peers) were significant mediators of the relation between movie alcohol exposure and alcohol consumption, even after controlling for demographic, child, and family factors associated with both movie exposure and alcohol consumption. Established psychological and interpersonal predictors of alcohol use mediate the effects of exposure to alcohol use in movies on adolescent alcohol consumption. The findings suggest that exposure to movie portrayals may operate through similar processes as other social influences, highlighting the importance of considering these exposures in research on adolescent risk behavior.

Intestinal fungi contribute to development of alcoholic liver disease.

PubMed

Yang, An-Ming; Inamine, Tatsuo; Hochrath, Katrin; Chen, Peng; Wang, Lirui; Llorente, Cristina; Bluemel, Sena; Hartmann, Phillipp; Xu, Jun; Koyama, Yukinori; Kisseleva, Tatiana; Torralba, Manolito G; Moncera, Kelvin; Beeri, Karen; Chen, Chien-Sheng; Freese, Kim; Hellerbrand, Claus; Lee, Serene Ml; Hoffman, Hal M; Mehal, Wajahat Z; Garcia-Tsao, Guadalupe; Mutlu, Ece A; Keshavarzian, Ali; Brown, Gordon D; Ho, Samuel B; Bataller, Ramon; Stärkel, Peter; Fouts, Derrick E; Schnabl, Bernd

2017-06-30

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.

Predictive Effects of Good Self-Control and Poor Regulation on Alcohol-Related Outcomes: Do Protective Behavioral Strategies Mediate?

PubMed Central

Pearson, Matthew R.; Kite, Benjamin A.; Henson, James M.

2016-01-01

In the present study, we examined whether use of protective behavioral strategies mediated the relationship between self-control constructs and alcohol-related outcomes. According to the two-mode model of self-control, good self-control (planfulness; measured with Future Time Perspective, Problem Solving, and Self-Reinforcement) and poor regulation (impulsivity; measured with Present Time Perspective, Poor Delay of Gratification, Distractibility) are theorized to be relatively independent constructs rather than opposite ends of a single continuum. The analytic sample consisted of 278 college student drinkers (68% women) who responded to a battery of surveys at a single time point. Using a structural equation model based on the two-mode model of self-control, we found that good self-control predicted increased use of three types of protective behavioral strategies (Manner of Drinking, Limiting/Stopping Drinking, and Serious Harm Reduction). Poor regulation was unrelated to use of protective behavioral strategies, but had direct effects on alcohol use and alcohol problems. Further, protective behavioral strategies mediated the relationship between good self-control and alcohol use. The clinical implications of these findings are discussed. PMID:22663345

Pathogenesis of liver cirrhosis.

PubMed

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-06-21

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

Pathogenesis of liver cirrhosis

PubMed Central

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-01-01

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

Risk factors for osteoporosis in liver cirrhosis patients measured by transient elastography.

PubMed

Zheng, Jian-Ping; Miao, Hai-Xiong; Zheng, Shao-Wei; Liu, Wei-le; Chen, Chu-Qun; Zhong, Hao-Bo; Li, Sheng-Fa; Fang, Yong-Ping; Sun, Chun-Han

2018-05-01

Osteoporosis or osteopenia is a common complication in patients with cirrhosis, but little is known about the risk factors for the occurrence of osteoporosis.Patients with liver cirrhosis due to chronic virus infection and alcoholic abuse were enrolled. Bone mineral density (BMD) was determined using dual-energy x-ray absorptiometry (DXA). Osteoporosis was diagnosed according to WHO criteria. The severity of liver stiffness was measured by Fibroscan. Demographic data, such as age, gender, weight, height, and body mass index (BMI), were collected. Logistic regression analysis was used to recognize the risk factors of osteoporosis in patients with cirrhosis.A total of 446 patients were included in this study: 217 had liver cirrhosis (male, 74.2%; mean age, 57.2 ± 10.27) and 229 were matched controls (male, 69%, mean age, 56.69 ± 9.37). Osteoporosis was found in 44 patients (44/217, 20.3%). The spine and hip BMD in cirrhotic patients were significantly lower than that in controls. When the cirrhotic and control subjects were stratified by age, gender, and BMI, the significant difference was also observed in women patients, patients older than 60, and patients with BMI < 18. Multivariate analysis showed that the older age [odds ratio (OR) = 1.78, P = .046], lower BMI (OR = 0.63, P = .049), greater fibroscan score (OR = 1.15, P = .009), and liver cirrhosis induced by alcohol liver disease (OR = 3.42, P < .001) were independently associated with osteoporosis in cirrhotic patients.Osteoporosis occurred in about one-fifth of patients with liver cirrhosis, which was associated with age, BMI, Fibroscan score, and alcohol liver disease related liver cirrhosis.

The Etiology of Cirrhosis is a Strong Determinant of Brain Reserve: A Multi-modal MR Imaging Study

PubMed Central

Ahluwalia, Vishwadeep; Wade, James B; Moeller, F Gerard; White, Melanie B; Unser, Ariel B; Gavis, Edith A; Sterling, Richard K; Stravitz, R Todd; Sanyal, Arun J; Siddiqui, Mohammad S; Puri, Puneet; Luketic, Velimir; Heuman, Douglas M; Fuchs, Michael; Matherly, Scott; Bajaj, Jasmohan S

2015-01-01

Background Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease severity and increase the patients’ vulnerability towards further deterioration. Aim To analyze brain reserve in abstinent alcoholic (Alc) compared to non-alcoholic (Nalc) cirrhosis patients in the context of hepatic encephalopathy (HE) and evaluate relative change in brain reserve between groups over time and before/after elective TIPS placement. Methods Cross-sectional study 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests followed by magnetic resonance (MR) imaging including 1-H MR Spectroscopy (MRS), Diffusion tensor (DTI) and T1-weighted imaging. Prospective study MRS on subset of 10 patients before/after TIPS placement. Another subset of 26 patients underwent MRS at least one year apart. Results Cross-sectional study Alc patients were worse on cognitive tests than Nalc. MR results suggest a greater effect of hyperammonemia, brain edema and significantly higher cortical damage in Alc as compared to Nalc patients. Effect of HE status on cognitive tests and brain reserve was more marked in Nalc than in Alc group. TIPS study Nalc patients showed a greater adverse relative change after TIPS compared to Alc group. 1-year follow-up Both groups remained stable between the two visits. However, Alc patients continued to show poor brain reserve than Nalc over time. Conclusions Patients with alcoholic cirrhosis, despite abstinence, have a poor brain reserve while, non-alcoholic cirrhosis patients have a greater potential for brain reserve deterioration after HE and TIPS. Information regarding the brain reserve in cirrhosis could assist medical teams to refine their communication and monitoring strategies for different etiologies. PMID:25939692

Cirrhosis and Portal Hypertension

MedlinePlus

... Kids and Teens Pregnancy and Childbirth Women Men Seniors Your Health Resources Healthcare Management End-of-Life ... familydoctor.org editorial staff Categories: Family Health, Men, Seniors, WomenTags: adult, alcoholic cirrhosis, elderly, jaundice, liver disease, ...

A functional polymorphism of the NFKB1 gene increases the risk for alcoholic liver cirrhosis in patients with alcohol dependence.

PubMed

Marcos, Miguel; Pastor, Isabel; González-Sarmiento, Rogelio; Laso, Francisco Javier

2009-11-01

The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-kappaB, the NF-kappaB inhibitor alpha (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-gamma in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC. A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the -94ins/delATTG NFKB1, 3'-UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance. We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC. The deletion allele of the -94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data.

PNPLA3 genetic variation in alcoholic steatosis and liver disease progression

PubMed Central

Hampe, Jochen; Trépo, Eric; Datz, Christian; Romeo, Stefano

2015-01-01

Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3’s function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients. PMID:26151055

Prevalence, Risk Factors and In-hospital Outcomes of QTc Interval Prolongation in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Qi, Xingshun; Hou, Feifei; Ning, Zheng; Zhang, Xintong; Deng, Han; Peng, Ying; Li, Jing; Wang, Xiaoxi; Li, Hongyu; Guo, Xiaozhong

2016-09-01

QTc interval prolongation is an electrocardiographic abnormality in liver cirrhosis. The objective of this study was to evaluate the prevalence, risk factors and in-hospital outcomes of QTc interval prolongation in Chinese patients with liver cirrhosis. This was a retrospective analysis of a total of 1,268 patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and June 2014. QTc interval data were collected from the medical records. QTc interval prolongation was defined as QTc interval > 440 milliseconds. The prevalence of QTc interval prolongation was 38.2% (485 of 1268). In the entire cohort, the risk factors for QTc interval prolongation included an older age, a higher proportion of alcohol abuse and ascites, higher bilirubin, blood urea nitrogen, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower red blood cell (RBC), hemoglobin (Hb), albumin (ALB), alanine aminotransferase and calcium. The in-hospital mortality was not significantly different between patients with and without QTc interval prolongation (2.1% versus 1.3%, P = 0.276). In the subgroup analyses of patients with hepatitis B virus or alcohol alone-related liver cirrhosis, the risk factors included higher bilirubin, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower RBC, Hb and ALB. In the subgroups analyses of patients with acute upper gastrointestinal bleeding or ascites, the risk factors included lower RBC, Hb and ALB. QTc interval prolongation was frequent in liver cirrhosis. Although QTc interval prolongation was positively associated with alcohol-related liver cirrhosis and more severe liver dysfunction, it did not significantly influence the in-hospital mortality. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

[Survival in patients with liver cirrhosis at the Durango, IMSS Regional General Hospital].

PubMed

Rodríguez-Hernández, Heriberto; Jacobo-Karam, Janett S; Castañón-Santillán, María del Carmen; Arámbula-Chávez, Mayela; Martínez-Aguilar, Gerardo

2002-01-01

In Mexico, hepatic cirrhosis mortality exhibits important regional differences. To analyze global survival of cirrhotic patients, according to etiology and functional status. Between March 1990 to August 1998, newly diagnosed patients with hepatic cirrhosis were included in a follow-up study. Subjects were analyzed monthly. Information on clinical evolution, complications, and dates of events (death) and complications were registered. Survival was estimated using Kaplan-Meier method. Ninety nine subjects were included in the survival analysis, 66 with alcoholic and 33 with viral cirrhosis (HCV and HBV in 24 and nine patients, respectively). Ninety seven percent of patients were decompensated at diagnosis, and 81% had ascites. Probabilities for survival in the entire series were 69.7, 37.6 and 23.6% at 24, 48, and 60 months, respectively. There were no significant differences in the survival of patients grouped according to etiology. When survival was analyzed by Child-Pugh score, it was slightly higher in the alcoholic cirrhosis group. In this study survival probability of patients with viral cirrhosis was lower than in patients with alcohol cirrhosis.

Impact of Cirrhosis on Resource Use and Inpatient Complications in Patients Undergoing Total Knee and Hip Arthroplasty.

PubMed

Newman, Jared M; Schiltz, Nicholas K; Mudd, Christopher D; Szubski, Caleb R; Klika, Alison K; Barsoum, Wael K

2016-11-01

Cirrhosis is a major cause of morbidity and mortality and is an important risk factor for complications in surgical patients. The purpose of this study was to investigate the association of cirrhosis with postoperative complications, length of stay (LOS), and costs among patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA). Using the Nationwide Inpatient Sample between 2000 and 2011, we identified patients who had a primary TKA or primary THA. TKA patients were divided into 2 groups: (1) cirrhosis (n = 41,464) and (2) no cirrhosis (n = 5,721,297) and THA patients were divided into 2 groups: (1) cirrhosis (n = 27,401) and (2) no cirrhosis (n = 2,622,539). Patient demographics, comorbidities, perioperative complications, LOS, and incremental costs were analyzed. An additional subgroup analysis by cirrhosis etiology was performed. Multivariable analysis revealed cirrhosis was associated with 1.55 (95% confidence interval: 1.47-1.63) times higher odds of any complication after TKA and 1.59 (1.50-1.69) higher odds after THA. Adjusted outcomes showed cirrhotic TKA patients had $1857 higher costs and 0.30 days longer LOS and THA cirrhotic patients had $1497 higher costs and 0.48 longer LOS. We found similar results for each cirrhosis subtype but alcohol-related had the highest resource use and complication rate. Patients with cirrhosis who are undergoing TKA or THA are at a significantly increased risk for perioperative complications, increased LOS, and higher costs. The perioperative complications and costs were highest among patients with alcohol-related cirrhosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Delinquency as a mediator of the relation between negative affectivity and adolescent alcohol use disorder.

PubMed

Shoal, Gavin D; Gudonis, Lauren C; Giancola, Peter R; Tarter, Ralph E

2007-12-01

This investigation examined mediators of the longitudinal relation between negative affectivity and the development of problematic drinking behavior in adolescent boys and girls. In the present study, 499 early adolescents completed inventories of negative affectivity, attitudes toward delinquency, personal delinquency, and affiliation with delinquent peers. Positive attitudes toward delinquency emerged as the most consistent mediator and strongly predicted drinking frequency in various situations. Compared with personal delinquency, both attitudes toward delinquency and peer delinquency were superior predictors of affect-related drinking. Our results also demonstrated that positive attitudes toward delinquency mediated the relation between negative affectivity and later development of an alcohol use disorder. These findings suggest that a proneness to unpleasant affect impacts adolescent drinking by heightening risk for general rejection of normative behavior, rather than by increasing drinking as a means of managing affect. The importance and implications of testing delinquency variables together in the same model are discussed.

Burden of Chronic Viral Hepatitis and Liver Cirrhosis in Brazil - the Brazilian Global Burden of Disease Study.

PubMed

de Carvalho, Juliana R; Villela-Nogueira, Cristiane A; Perez, Renata M; Portugal, Flavia B; Flor, Luisa S; Campos, Mônica R; Schramm, Joyce M A

Data on epidemiology of liver diseases in Brazil is scarce. This study aimed to estimate the burden of chronic viral hepatitis and liver cirrhosis in the country. The indicator used was disability-adjusted life year (DALY), a sum of years of life lost due to premature mortality (YLL) and years lived with disability (YLD). Liver cirrhosis was analyzed in etiologic categories and cirrhosis of viral origin was considered part of the burden of chronic hepatitis. There were 57,380 DALYs (30.3 per 100,000 inhabitants) attributable to chronic hepatitis B and cirrhosis due to hepatitis B, with 41,262 DALYs in men. Most burden was caused by YLL (47,015 or 24.8/100,000) rather than YLD (10,365 or 5.5/100,000). Chronic hepatitis C and cirrhosis due to hepatitis C were responsible for 207,747 DALYs (109.6/100,000), of which 137,922 were YLL (72.7/100,000) and 69,825 (36.8/100,000) were YLD, with a higher proportion of DALYs in men (73.9%). Cirrhosis due to alcohol or other causes had a total of 536,169 DALYs (1,4% of total DALYs in Brazil), with 418,272 YLL (341,140 in men) and 117,897 YLD (97,965 in men). Highest DALYs' rates occurred at ages 60-69 in chronic hepatitis and at ages 45-59 in cirrhosis due to alcohol or other causes. Chronic viral hepatitis and liver cirrhosis are responsible for a significant burden in Brazil, affecting mainly men and individuals still in their productive years. Most burden is related to non-viral causes of cirrhosis, with a major contribution of alcohol.

Normative Beliefs, Expectancies, and Alcohol-Related Problems among College Students; Implications for Theory and Practice.

ERIC Educational Resources Information Center

Fearnow-Kenny, Melodie D.; Wyrick, David L.; Hansen, William B.; Dyreg, Doug; Beau, Dan B.

2001-01-01

Investigation (1) examined interrelations among normative beliefs, alcohol expectancies, and alcohol-related problems, and (2) investigated whether alcohol-related expectancies mediate associations between normative beliefs and alcohol-related problems. Analyses revealed that alcohol expectancies mediate the relationship between normative beliefs…

Exposure to alcohol advertisements and teenage alcohol-related problems.

PubMed

Grenard, Jerry L; Dent, Clyde W; Stacy, Alan W

2013-02-01

This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents' jobs, and parents' education. Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence.

Exposure to Alcohol Advertisements and Teenage Alcohol-Related Problems

PubMed Central

Dent, Clyde W.; Stacy, Alan W.

2013-01-01

OBJECTIVE: This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. METHODS: A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents’ jobs, and parents’ education. RESULTS: Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. CONCLUSIONS: Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence. PMID:23359585

Challenges in transplantation for alcoholic liver disease.

PubMed

Berlakovich, Gabriela A

2014-07-07

Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

Nitric oxide-mediated pathogenesis during nicotine and alcohol consumption.

PubMed

Cooper, R G; Magwere, T

2008-01-01

Nitric oxide (NO) is formed by different cell types in response to a variety of physiological and patho-physiological stimuli. The intake of nicotine and/or alcohol has patho-physiological effects on organ function, and the progression of alcohol-/tobacco-related diseases seem to be directly influenced by NO-mediated mechanisms. Nicotine has an adverse influence on blood vessel functionality, repair and maintenance. Chronic nicotine exposure augments atherosclerosis by enhancing the production of proinflammatory cytokines by macrophages which then activate atherogenic NF-kB target genes in aortic lesions. Alcohol produces NO which speeds up the apoptosis of neutrophils. Alcohol sensitizes the liver to endotoxemic shock. Nitrosative stress and increased basal levels of NO contribute to tumour growth. The progression of disease seems to be directed via a definite NO-mediated mechanism. This review gives an insight into how intake of tobacco and alcohol may affect quality of life.

[Treatment of liver cirrhosis - actually possibility of ambulant internist].

PubMed

Ehrmann, Jiří; Aiglová, Květa; Konečný, Michal; Procházka, Vlastimil; Vrzalová, Drahomíra

There are 40 000-60 000 patients with cirrhosis in the Czech Republic. 2 000 die of this disease yearly. This group of patients needs a complex treatment and it is mostly an internist cooperating with other specialists. The most important for an ambulant internist is to diagnose the disease as soon as possible and start with treatment of chronic liver disease that could lead to a cirrhosis. It means especially chronic viral hepatitis, alcoholic or non-alcoholic steatosis/steatohepatitis, auto-immune liver damage and metabolic disease. The next step is to diagnose the cirrhosis in time when it is in no manifest stage. The third step is to diagnose and treat the liver decompensation. It means consequences of the portal hypertension, it is ascit, esophageal or gastric varices, hepatorenal syndrome. Next there are consequences of the metabolic insufficiency, it is icterus, coagulopathy and hepatic encephalopathy. It is necessary to diagnose and cure cholestasis from the very first extrahepatic causes. For a successful treatment of the hepatocellular carcinoma originated almost exclusively in the grounds of the cirrhosis must be early diagnosed. The ambulant internist respective hepatologist must diagnose the stage of the cirrhosis and decide when a hospitalization is necessary. Also a close cooperation with other specialists is urgent if it is about a liver transplantation. The treatment of successive stages of the cirrhosis is a topic of the showed educational article. compensated/decompensated liver cirrhosis - diet/nutrition in liver cirrhosis - etiology and diagnose of liver cirrhosis - treatment of liver insufficiency/failure - treatment of portal hypertension and its complications.

Drinking motives mediate the relationship between reinforcing efficacy and alcohol consumption and problems.

PubMed

Yurasek, Ali M; Murphy, James G; Dennhardt, Ashley A; Skidmore, Jessica R; Buscemi, Joanna; McCausland, Claudia; Martens, Matthew P

2011-11-01

Several studies have shown that demand curve indices of the reinforcing efficacy of alcohol (i.e., reports of hypothetical alcohol consumption and expenditures across a range of drink prices) are associated with alcohol-related outcomes. A next logical step in this area of research is to examine potential mediators of this direct relationship. It is possible that enhancement and coping drinking motives serve as an intermediary of the reinforcing efficacy-alcohol use relationship, such that higher reinforcing efficacy is associated with increased motivation to drink, which is then associated with greater alcohol use and problems. Data were collected from 215 college undergraduates who reported drinking in the past 30 days. The demand curve reinforcing efficacy indices O(max) (maximum alcohol expenditure) and intensity (consumption level when drinks were free) demonstrated the strongest and most consistent associations with alcohol use, problems, and motives. Results from two structural equation models indicated that enhancement and coping motives mediated the relationship between reinforcing efficacy and alcohol use and alcohol-related problems. These results suggest that the motivational effects of the behavioral economic variable reinforcing efficacy on problematic alcohol use are in part mediated by increases in enhancement and coping motives for drinking.

Delinquency as a Mediator of the Relation between Negative Affectivity and Adolescent Alcohol Use Disorder

PubMed Central

Shoal, Gavin D.; Gudonis, Lauren C.; Giancola, Peter R.; Tarter, Ralph E.

2007-01-01

This investigation examined mediators of the longitudinal relation between negative affectivity and the development of problematic drinking behavior in adolescent boys and girls. In the present study, 499 early adolescents completed inventories of negative affectivity, attitudes toward delinquency, personal delinquency, and affiliation with delinquent peers. Positive attitudes toward delinquency emerged as the most consistent mediator and strongly predicted drinking frequency in various situations. Compared with personal delinquency, both attitudes toward delinquency and peer delinquency were superior predictors of affect-related drinking. Our results also demonstrated that positive attitudes toward delinquency mediated the relation between negative affectivity and later development of an alcohol use disorder. These findings suggest that a proneness to unpleasant affect impacts adolescent drinking by heightening risk for general rejection of normative behavior, rather than by increasing drinking as a means of managing affect. The importance and implications of testing delinquency variables together in the same model are discussed. PMID:17490823

Alcohol dehydrogenase ADH2-1 and ADH2-2 allelic isoforms in the Russian population correlate with type of alcoholic disease.

PubMed

Ogurtsov, Pavel P.; Garmash, Irina V.; Miandina, Galina I.; Guschin, Alexander E.; Itkes, Alexander V.; Moiseev, Valentin S.

2001-09-01

The frequency ADH2-2 allele in the Moscow urban population and a correlation between the ADH2-2 allele, alcoholic dependence without cirrhosis, symptomatic alcoholic cirrhosis and status on hepatitis B and C infection have been studied. One hundred and twenty-three inhabitants of Moscow (50 healthy donors, 36 patients with alcoholic cirrhosis (subdivided into infected and uninfected by HBV and/or HCV) and 37 patients with alcoholic dependence) of a similar age/sex and drinking pattern have been analysed. The frequency of 41% for ADH2-2 allele is characteristic for an urban Moscow population. This value is intermediate between that found for Asian peoples and for Central and Western Europe. There is a negative correlation between the ADH2-2 allele and alcohol misuse (both alcoholic dependence and alcoholic cirrhosis). This correlation is expressed more in alcoholic dependence. In spite of the possession of the ADH2-2 allele (or genotype ADH2-1/2), alcohol misuse increases the risk of cirrhosis. At the same time, positive status for active hepatitis B, C or combined infection B + C (replication markers HBV-DNA or HCV-RNA) increases the risk for symptomatic alcoholic cirrhosis in alcohol abusing patients, independently of ADH2 genotype.

Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care hospital in South Auckland, New Zealand.

PubMed

Hsiang, J C; Bai, W W; Raos, Z; Stableforth, W; Upton, A; Selvaratnam, S; Gane, E J; Gerred, S J

2015-02-01

Liver cirrhosis is an important cause of morbidity and mortality; however, little is known about its impact in New Zealand. We aim to determine the disease burden, epidemiology and outcomes of cirrhotic patients. This is a retrospective study of cirrhosis patients under secondary public hospital care in a geographically defined region, between the years 2000 and 2011. Cirrhosis complications and mortality was recorded. Poisson log-linear regression analysis was performed for incidence rate ratio (IRR) and Cox regression analysis was used to analyse time-related events. Seven hundred and forty-six cirrhotic patients were analysed; most were European/Other (39.9%), Pacific islanders (21.6%), Southeast Asian/Chinese (17.8%) and Maori (12.3%). 68.4% were male. The common primary aetiologies for cirrhosis were chronic hepatitis B (CHB) cirrhosis (37.3%), alcoholic liver disease (ALD) cirrhosis (24.1%), chronic hepatitis C (CHC) cirrhosis (22.3%) and non-alcoholic fatty liver disease (NAFLD) cirrhosis (16.4%). The hepatocellular carcinoma (HCC) mortality rates were highest in NAFLD and CHB cirrhosis groups (3.0 and 3.1 per 100 patient-year respectively), compared with ALD and CHC groups (2.2 and 1.4 per 100 patient-year, all P < 0.05 respectively). Patients with ALD and NAFLD cirrhosis had the highest all-cause and non-HCC mortality rate compared with viral hepatitis cirrhosis groups. The IRR for HCC incidence, liver-related mortality and HCC mortality were 1.087, 1.098 and 1.114, respectively (all P < 0.001), suggesting increasing incidence and disease burden over the study period. The number of cirrhotic patients in secondary care is increasing steadily. Cirrhosis complications and mortality rates are also rising, particularly the incidence and mortality of HCC. © 2014 Royal Australasian College of Physicians.

[Etiology and complications of liver cirrhosis: data from a German centre].

PubMed

Sivanathan, V; Kittner, J M; Sprinzl, M F; Weinmann, A; Koch, S; Wiltink, J; Nguyen-Tat, M; Marquardt, J U; Wörns, M A; Zimmermann, T; Lang, H; Galle, P R; Schattenberg, J M

2014-09-01

Liver cirrhosis develops as a terminal complication of chronic liver disease. The clinical course is determined by the underlying etiology and the accompanying risk factors, which are influenced by the geographic and cultural background. A total of 236 patients (159 men, 77 women, median age 57 [22-81] years) were included for retrospective analysis between July 2012 and February 2014 using standardized questionnaires during an outpatient visit at a hepatology clinic. The most common etiologies of liver cirrhosis were related to alcohol consumption (52 %), chronic hepatitis C (28 %) or hepatitis B (14 %) infection and NASH (nonalcoholic steatohepatitis, 6 %). At the time of presentation 55 % patients had compensated cirrhosis corresponding to Child-Turcotte-Pugh (CTP) stage A, while 45 % were in a decompensated stage (30 % CTP B and 15 % CTP C). Subgroups were analyzed for the incidence of complications and the emergence of infections. Most frequently esophageal varices (60 %) and ascites (49 %) were observed, followed by pleural effusion (14 %), hepatic encephalopathy (25 %) or hepatorenal syndrome (18 %). 16 % of patients exhibited infection based on clinical criteria. An infective agent was isolated in 38 % of all cases with infection and of those 50 % were gram positive bacteria. In multivariate analysis only the presence of ascites was an independent risk factor for infection. Despite improved medical therapies for viral hepatitis, these were the most frequent causes of liver cirrhosis, closely followed by alcoholic cirrhosis. The observed complications included bacterial infection and complication related to portal hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

Genetics Home Reference: cryptogenic cirrhosis

MedlinePlus

... likely result from a condition called non-alcoholic fatty liver disease (NAFLD). In NAFLD, fat accumulates in the ... Information & Resources MedlinePlus (5 links) Encyclopedia: Cirrhosis Encyclopedia: Fatty Liver--Nonalcoholic Encyclopedia: Liver Cancer--Hepatocellular Carcinoma Health Topic: ...

Predictive value of liver and spleen stiffness in advanced alcoholic cirrhosis with refractory ascites.

PubMed

Lindner, Franziska; Mühlberg, Reinhard; Wiegand, Johannes; Tröltzsch, Michael; Hoffmeister, Albrecht; Keim, Volker; Karlas, Thomas

2018-06-01

 Recurrent ascitic decompensation is a frequent complication of advanced alcoholic liver disease. Ascites can be controlled by transjugular intrahepatic portosystemic shunt (TIPS) implantation, but specific pre-procedural outcome predictors are not well established. Liver and spleen stiffness measurement (LSM, SSM) correlate with outcome of compensated liver disease, but data for decompensated cirrhosis disease are scarce. Therefore, the predictive value of LSM and SSM was evaluated in patients with refractory ascites treated with TIPS insertion or receiving conservative therapy.  Patients with alcoholic liver cirrhosis and recurrent or refractory ascites were stratified according to TIPS eligibility. LSM was prospectively assessed by transient elastography (TE, XL probe) and point shear wave elastography (pSWE). pSWE was also used for SSM. The primary study endpoint was transplant-free survival after 12 months. In addition, correlation of LSM and SSM with TIPS complications was analyzed.  43 patients (16 % female, age 55.5 [28.6 - 79.6] years) were recruited, n = 20 underwent TIPS and n = 23 were treated with repeated paracenteses only. 15 patients died and five underwent liver transplantation during follow-up. LSM and SSM at baseline did not predict the patients' outcome in the TIPS cohort and in patients with conservative therapy. SSM was increased in two cases with spontaneous TIPS occlusion and declined after revision.  LSM and SSM cannot be recommended for risk stratification in cirrhotic patients with refractory ascites. SSM may be useful in monitoring TIPS function during follow-up. © Georg Thieme Verlag KG Stuttgart · New York.

Attitudes as mediators of the longitudinal association between alcohol advertising and youth drinking.

PubMed

Morgenstern, Matthis; Isensee, Barbara; Sargent, James D; Hanewinkel, Reiner

2011-07-01

To test the hypothesis that changes in alcohol-related attitudes and expectancies mediate the effect of alcohol advertising on youth drinking. Longitudinal survey with a 9-month interval. Twenty-nine public schools in 3 German states. A total of 2130 sixth- to eighth-grade students (age range, 11-17 years; mean, 12.2 years) who were nondrinkers at baseline. Exposure to alcohol and nonalcohol advertising was measured at baseline with masked images of 17 commercial advertisements with all brand information digitally removed; students indicated contact frequency and brand names. Positive attitudes toward alcohol, current alcohol use, lifetime binge drinking. A total of 581 of the students (28%) started to drink alcohol during the observation period. Alcohol use initiation was positively related to baseline alcohol advertisement exposure. This effect of alcohol advertisement exposure on alcohol use was partially mediated by a change in alcohol-related attitudes, which explained about 35% of the total effect after controlling for baseline covariates and exposure to other advertising contents. The analysis revealed similar results for binge-drinking initiation. More favorable attitudes about alcohol may be one path through which alcohol advertising exerts behavioral influence.

Review article: the management of cirrhosis in women.

PubMed

Allen, A M; Hay, J E

2014-11-01

There are differences in the predisposition, natural history of liver disease, complications and treatment response between men and women. To review clinical differences in cirrhosis between men and women and to address unique management issues of fertility, pregnancy and contraception in this patient population. PubMed and MEDLINE were searched using the terms 'cirrhosis' and 'chronic liver disease', each cross-referenced with specific liver diseases, as well as terms such as 'cancer', 'hepatocellular carcinoma', 'smoking', 'liver transplantation', 'metabolic bone disease', 'fertility',' pregnancy' and 'contraception'. Pre-menopausal status is protective in viral hepatitis C and non-alcoholic steatohepatitis. However, smoking, especially in combination with alcohol, is a stronger risk factor for cirrhosis and malignancies in women with chronic liver disease compared to men, although they are less likely than men to develop hepatocellular carcinoma. Women with cirrhosis have more osteopenic bone disease than men and require active management. Successful pregnancy is possible in well-compensated cirrhosis or with mild portal hypertension, although the maternal and foetal mortality and morbidity are higher than in the general population. The maternal risk correlates with liver disease severity and derives mostly from variceal bleeding. The choices for contraception in compensated cirrhosis are generally the same as for the general population. Women with cirrhosis are disadvantaged by the current MELD system of organ allocation, at least in part due to body size. The management of women with chronic liver disease is unique in regards to counselling, screening for complications, fertility and pregnancy. © 2014 John Wiley & Sons Ltd.

A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

PubMed Central

Li, R; Barton, HA; Maurer, TS

2015-01-01

Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions. PMID:26225262

Relation of attachment style to family history of alcoholism and alcohol use disorders in early adulthood.

PubMed

Vungkhanching, Martha; Sher, Kenneth J; Jackson, Kristina M; Parra, Gilbert R

2004-07-15

The present study examined the association between paternal alcoholism and attachment style in early adulthood and sought to determine whether attachment style might, at least partially, mediate intergenerational risk for alcoholism. The current report focuses on the cross-sectional relation between family history (FH) of alcoholism, attachment styles, and alcohol use disorders (AUD) when cohort members were, on average, 29 years old (N = 369; 46% male; 51% FH+). Results indicated that FH+ participants were more likely to have insecure attachment, characterized by fearful-avoidant and dismissed-avoidant styles. Additionally, fearful-avoidant and dismissed-avoidant attachment styles were related to the presence of an AUD even after controlling for sex and FH (P < 0.05). There was little evidence, however, that attachment style mediated the relation between paternal alcoholism and AUD in offspring; the FH-AUD association was only negligibly reduced when the effect of attachment style was controlled. Our findings suggest that insecure attachment style is a risk factor for AUD, independent of familial risk for alcoholism.

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

Histocompatibility antigens in patients with alcoholic liver disease in Scotland and northeastern England: failure to show an association.

PubMed Central

Mills, P R; MacSween, R N; Dick, H M; Hislop, W S

1988-01-01

A study of HLA-A and B antigens in 248 patients with biopsy diagnosed alcoholic liver disease was conducted to examine for a genetic predisposition to alcohol related liver injury. No statistically significant differences were established for 8 HLA-A and 16 HLA-B antigens between normal healthy controls (n = 342) and patients with alcoholic fatty liver (n = 86), alcoholic hepatitis (n = 63), active alcoholic cirrhosis (n = 64) and inactive alcoholic cirrhosis (n = 35). It is concluded that no HLA-A or B locus genetic susceptibility to alcoholic related injury could be shown. PMID:3162222

Incidence, clinical presentation and mortality of liver cirrhosis in Southern Sweden: a 10-year population-based study.

PubMed

Nilsson, E; Anderson, H; Sargenti, K; Lindgren, S; Prytz, H

2016-06-01

In Sweden, the most common causes of liver cirrhosis are alcohol overconsumption and hepatitis C. However, recent data on the clinical characteristics of Swedish patients with cirrhosis are scarce. To determine the incidence, clinical presentation, aetiological spectrum and survival rates of liver cirrhosis in Southern Sweden from 2001 to 2011. We used population-based medical registries to conduct a cohort study of all patients with liver cirrhosis in the southernmost region of Sweden with a population of 1.17 million. Medical records and histopathology data were reviewed. Patients were classified according to aetiology, and clinical parameters were registered. Patients were followed until death or December 2014. A total of 1317 patients with cirrhosis were identified. The crude annual incidence of cirrhosis was estimated at 14.1/100 000. The most common aetiology was alcohol overconsumption with or without additional causes of cirrhosis (58%) followed by HCV alone (13%) and cryptogenic cirrhosis (12%). At diagnosis, ascites occurred in 43%, variceal bleeding in 6% and overt encephalopathy in 4%. The median follow-up was 4.3 years. The total 1-, 5- and 10-year survival rates were 79%, 47% and 27% respectively. Survival rates were better for women than for men. A 10-year cumulative incidence of transplantation was 7.3%. Mortality was worst for alcoholic cirrhosis with concomitant HCV when adjusted for age and gender. Sweden continues to have a low incidence of cirrhosis compared with other European countries. Mortality varies with gender, aetiology and severity at diagnosis. Patients with alcoholic cirrhosis with concomitant HCV infection fare worst. © 2016 John Wiley & Sons Ltd.

Alcohol Expectancies as Potential Mediators of Parent Alcoholism Effects on the Development of Adolescent Heavy Drinking.

ERIC Educational Resources Information Center

Colder, Craig R.; Chassin, Laurie; Stice, Eric M.; Curran, Patrick J.

1997-01-01

Used latent growth curve modeling to examine adolescent alcohol expectancies as mediators of effects of parent alcoholism on escalation in adolescent heavy drinking. Found that parent alcoholism directly affected adolescent heavy drinking. Alcohol expectancies did not mediate parent alcoholism effects. Cross-sectional evidence suggested that…

Family Functioning and Adolescent Alcohol Use: A Moderated Mediation Analysis

PubMed Central

Ohannessian, Christine McCauley; Flannery, Kaitlin M.; Simpson, Emily; Russell, Beth S.

2016-01-01

The primary goals of this longitudinal study were to examine the relationship between family functioning and adolescent alcohol use and to examine whether depressed mood mediates this relationship. An additional goal was to explore whether these relations were moderated by gender. The sample included 1,031 high school students from the Mid-Atlantic United States. Participants completed surveys in school during the spring of 2007, 2008, and 2009. Path analysis results indicated that family functioning predicted alcohol use for girls. Moreover, depressed mood mediated this relationship. None of the direct paths between family functioning and adolescent alcohol use were significant for boys. However, similar to girls, depressed mood negatively predicted alcohol use for boys. Taken together, the findings highlight the need for prevention programs targeting adolescent substance use to consider gender-specific trajectories. PMID:26994346

Histological versus clinical cirrhosis in chronic hepatitis C: does race/ethnicity really matter?

PubMed

Kohla, Mohamed; Iwata, Shunpei; Ea, Roth; Keyhan, Sanaz; Taylor, Robert; Yu, Mimi C; Groshen, Susan; Bonacini, Maurizio

2012-03-01

Liver fibrosis progression in hepatitis C virus (HCV) infection has been in part associated with race/ethnicity. Little is known of the frequency of clinical cirrhosis in Asian patients in the US. To compare histological and clinical features of chronic hepatitis C (CHC) in a multiethnic cohort of patients. Retrospective query of an electronic medical registry for CHC patients evaluated from 1999 to 2005. Histological cirrhosis was defined as advanced METAVIR fibrosis score at biopsy. Clinical cirrhosis was defined as any of: varices, ascites, or splenomegaly. Liver cirrhosis was defined as either histological or clinical cirrhosis. Chi-square tests, t tests, and logistic regression method were used for data analysis. Six hundred and ninety-two patients were categorized into four racial-ethnic groups: 292 Caucasian (C), 145 Hispanic (H), 121 African American (AA), and 134 Asian (As) patients. Median age of AA (54 years) and As (53) was higher than C (52), or H (50) (p < 0.05). H patients had a higher percentage of alcohol abuse (60%) than AA and C (42-44%) and As (14%; p < 0.0001). Body mass index (BMI) was significantly lower in Asians compared to all other groups (p < 0.0001). Features of the metabolic syndrome were common, ranging from 28% in As to 72% in H patients. Liver cirrhosis was found in 53% H, 35% C, 29% As, and 19% AA. In multivariable analysis, only alcohol abuse, BMI, diabetes mellitus (DM), and age were significantly associated with liver cirrhosis. There was a trend for AA to have less cirrhosis, either histological or clinical (p = 0.08). Using only histology, liver cirrhosis was significantly underestimated. In our cohort, severity of CHC was not clearly affected by race when alcohol use and features of the metabolic syndrome were taken into consideration. However, there was a trend for African Americans to have lower cirrhosis rates.

Inositol-requiring enzyme 1-mediated endoplasmic reticulum stress triggers apoptosis and fibrosis formation in liver cirrhosis rat models.

PubMed

Jiang, Tianpeng; Wang, Lizhou; Li, Xing; Song, Jie; Wu, Xiaoping; Zhou, Shi

2015-04-01

Long‑term and advanced cirrhosis is usually irreversible and often coincides with variceal hemorrhage or development of hepatocellular carcinoma; therefore, liver cirrhosis is a major cause of morbidity and mortality globally. The aim of the present study was to investigate the specific mechanism behind the formation of fibrosis or cirrhosis using rat models of hepatic fibrosis. The cirrhosis model was established by intraperitoneally administering dimethylnitrosamine to the rats. Hematoxylin and eosin staining was performed on the hepatic tissues of the rats to observe the fibrosis or cirrhosis, and western blot analysis was employed to detect α‑smooth muscle actin and desmin protein expression. Flow cytometric analysis was used to examine early and late apoptosis, and the protein and mRNA expression of endoplasmic reticulum (ER) stress-associated unfolded protein response (UPR) pathway proteins and apoptotic proteins [C/EBP homologous protein (CHOP) and caspase‑12] was detected by western blotting and the reverse-transcription polymerase chain reaction, respectively. The results indicated that the cirrhosis model was established successfully and that fibrosis was significantly increased in the cirrhosis model group compared with that in the normal control group. Flow cytometric analysis showed that early and late apoptosis in the cirrhosis model was significantly higher compared with that in the control group. The expression of the UPR pathway protein inositol-requiring enzyme (IRE) 1, as well as the expression of CHOP, was increased significantly in the cirrhotic rat tissues compared with that in the control group tissues (P<0.05). In conclusion, apoptosis was clearly observed in the hepatic tissue of cirrhotic rats, and the apoptosis was caused by activation of the ER stress-mediated IRE1 and CHOP.

Impact of Alcohol Tax Increase on Maryland College Students' Alcohol-Related Outcomes.

PubMed

Smart, Mieka J; Yearwood, Safiya S; Hwang, Seungyoung; Thorpe, Roland J; Furr-Holden, C Debra

2018-05-12

This study A) assessed whether levels of alcohol-related disciplinary actions on college campuses changed among MD college students after the 2011 Maryland (MD) state alcohol tax increase from 6% to 9%, and B) determined which school-level factors impacted the magnitude of changes detected. A quasi-experimental interrupted time series (ITS) analysis of panel data containing alcohol-related disciplinary actions on 33 MD college campuses in years 2006-2013. Negative binomial regression models were used to examine whether there was a statistically significant difference in counts of alcohol-related disciplinary actions comparing time before and after the tax increase. The ITS anaysis showed an insignificant relationship between alcohol-related disciplinary actions and tax implementation (β = -.27; p =.257) but indicated that alcohol-related disciplinary actions decreased significantly over the time under study (β = -.05; p =.022). Alcohol related disciplinary actions did decrease over time in the years of study, and this relationship was correlated with several school-level characteristics, including school price, school funding type, types of degrees awarded, and specialty. School price may serve as a proxy mediator or confounder of the effect of time on disciplinary actions.

Diagnostic significance of nitrates and nitrites and L-arginine, in development of hepatorenal syndrome in patients with end stage alcoholic liver cirrhosis.

PubMed

Nickovic, Vanja; Kocic, Gordana; Bjelakovic, Goran; Pavlovic, Radmila; Stojanovic, Ivana; Katanic, Radoslav; Stojanovic, Svetlana; Djindjic, Boris

2013-01-01

Hepatorenal syndrome (HRS) represents a complication of the end-stage liver cirrhosis. The aim of the present study was to analyze concentrations of nitrates and nitrites (NO2 + NO3) and L-arginine in patients with liver cirrhosis and HRS as a possible predictive marker for the development of HRS. The research was performed in a group of 28 patients with cirrhosis and HRS, a group of 22 patients suffering from cirrhosis without HRS and a control group comprised of 42 healthy voluntary blood donors. In patients with end-stage alcoholic liver cirrhosis, with HRS, the concentrations of NO2 + NO3 increased and correlated with the degree of cirrhosis progression, compared to patients without HRS and significantly higher compared to the control group. The level of NO2 + NO3 was in a positive correlation with the degree of liver damage de Ritis coefficient (HRS = 0.72; cirrhosis: = 0.55; control = -0.10). Significant positive correlation was found between NO2 + NO3 concentration and inflammatory marker C-reactive protein (HRSC = 0.75; cirrhosis = 0.70, control = -0.25). The correlation between NO2 + NO3 concentration and creatinine concentration in patients with HRS was significantly higher compared to patients without HRS (HRS = 0.82; cirrhosis = 0.32; control = -0.25). By using binary regression analysis, on the basis of clinical criteria of HRS diagnosis, the strongest independent positive predictor for HRS development was NO2 + NO3, associated with 45.02 times higher incidence of HRS, compared to arginine (12.7 times higher incidence), creatinine (13.1 times higher incidence), and AST/ALT ratio (10.55 higher incidence of HRS). Since the determination of NO2 + NO3 represents a reliable and easily applicable method, it may be used as an early predictive marker for HRS development.

Non-invasive prediction of oesophageal varices in cirrhosis

PubMed Central

Sen, Sambit; Griffiths, William JH

2008-01-01

Non-invasive predictors of varices in cirrhosis would reduce the need for screening endoscopies. Platelet count and spleen size have been shown to be useful parameters, in mixed groups of cirrhotics with different aetiologies. We evaluated this in two homogeneous groups with cirrhosis due to hepatitis C and alcohol. Non-invasive predictors appear promising in the former group, but less so in the latter group. PMID:18416480

Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction.

PubMed

Henriksen, Jens H; Bendtsen, Flemming; Møller, Søren

2015-08-01

Acid-base disturbances were investigated in patients with cirrhosis in relation to hemodynamic derangement to analyze the hyperventilatory effects and the metabolic compensation. A total of 66 patients with cirrhosis and 44 controls were investigated during a hemodynamic study. Hyperventilatory hypocapnia was present in all patients with cirrhosis and progressed from Child class A to C (P<0.01). Arterial pH increased significantly from class A to C (P<0.001) and was correlated inversely to the mean arterial blood pressure (r=-0.30, P<0.02), systemic vascular resistance (r=-0.25, P<0.05), indocyanine green clearance (r=-0.37, P<0.005), and serum sodium (r=-0.38, P<0.002). Metabolic compensation was shown by a reduced standard base excess in all patients (P<0.001). Standard base excess contained elements related to changes in serum albumin, water dilution, and effects of unidentified ions (all P<0.001). A significant hepatic component in the acid-base disturbances could not be identified. Hypocapnic alkalosis is related to disease severity and hyperdynamic systemic circulation in patients with cirrhosis. The metabolic compensation includes alterations in serum albumin and water retention that may result in a delicate acid-base balance in these patients.

Effects of an online alcohol education course among college freshmen: an investigation of potential mediators.

PubMed

Paschall, Mallie J; Ringwalt, Chris; Wyatt, Todd; Dejong, William

2014-04-01

The authors investigated possible mediating effects of psychosocial variables (perceived drinking norms, positive and negative alcohol expectancies, personal approval of alcohol use, protective behavioral strategies) targeted by an online alcohol education course (AlcoholEdu for College) as part of a 30-campus randomized trial with 2,400 first-year students. Previous multilevel analyses have found significant effects of the AlcoholEdu course on the frequency of past-30-day alcohol use and binge drinking during the fall semester, and the most common types of alcohol-related problems. Exposure to the online AlcoholEdu course was inversely related to perceived drinking norms but was not related to any of the other psychosocial variables. Multilevel analyses indicated at least partial mediating effects of perceived drinking norms on behavioral outcomes. Findings of this study suggest that AlcoholEdu for College affects alcohol use and related consequences indirectly through its effect on student perceptions of drinking norms. Further research is needed to better understand why this online course did not appear to affect other targeted psychosocial variables.

The Effect of Approach/Avoidance Training on Alcohol Consumption Is Mediated by Change in Alcohol Action Tendency

PubMed Central

Sharbanee, Jason M.; Hu, Litje; Stritzke, Werner G. K.; Wiers, Reinout W.; Rinck, Mike; MacLeod, Colin

2014-01-01

Training people to respond to alcohol images by making avoidance joystick movements can affect subsequent alcohol consumption, and has shown initial efficacy as a treatment adjunct. However, the mechanisms that underlie the training’s efficacy are unknown. The present study aimed to determine 1) whether the training’s effect is mediated by a change in action tendency or a change in selective attention, and 2) whether the training’s effect is moderated by individual differences in working memory capacity (WMC). Three groups of social drinkers (total N = 74) completed either approach-alcohol training, avoid-alcohol training or a sham-training on the Approach-Avoidance Task (AAT). Participants’ WMC was assessed prior to training, while their alcohol-related action tendency and selective attention were assessed before and after the training on the recently developed Selective-Attention/Action Tendency Task (SA/ATT), before finally completing an alcohol taste-test. There was no significant main effect of approach/avoidance training on alcohol consumption during the taste-test. However, there was a significant indirect effect of training on alcohol consumption mediated by a change in action tendency, but no indirect effect mediated by a change in selective attention. There was inconsistent evidence of WMC moderating training efficacy, with moderation found only for the effect of approach-alcohol training on the AAT but not on the SA/ATT. Thus approach/avoidance training affects alcohol consumption specifically by changing the underlying action tendency. Multiple training sessions may be required in order to observe more substantive changes in drinking behaviour. PMID:24465750

The usefulness of the sum of relative enhancement ratio in making a differential diagnosis of hepatocellular carcinoma from cirrhosis-related nodules.

PubMed

Yoon, Ki Woong; Song, Ji Soo; Han, Young Min

2014-01-01

To estimate the diagnostic accuracy of the sum of relative enhancement ratio (sRER) in making a differential diagnosis of hepatocellular carcinoma (HCC) from benign cirrhosis-related nodules. Eighteen benign cirrhosis-related nodules and 18 HCCs were evaluated. Three radiologists independently reviewed computed tomography images using visual assessment and sRER. sRER was estimated by adding region-of-interest measurement in the arterial phase and the delayed phase. Diagnostic performance and accuracy were evaluated. The mean values of sRER were significantly higher in HCCs than in benign cirrhosis-related nodules. The sRER method improved diagnostic accuracy of differentiating HCCs from benign cirrhosis-related nodules. Copyright © 2014 Elsevier Inc. All rights reserved.

Medical and Obstetric Complications Among Pregnant Women With Liver Cirrhosis.

PubMed

Palatnik, Anna; Rinella, Mary E

2017-06-01

To evaluate clinical characteristics and obstetric outcomes in pregnant women with liver cirrhosis. This was a retrospective matched cohort study of women with liver cirrhosis between January 2005 and January 2016 in a university hospital. Women in a case group were matched to women in a control group according to year of delivery, age, body mass index, and parity in a 1:4 ratio. Bivariable and multivariable analyses were performed to compare the prevalence of the primary composite outcome, which included any one of the following: fetal or neonatal demise, placental abruption, preeclampsia, preterm delivery at less than 37 weeks of gestation, and small-for-gestational age neonate between women in the case group and those in the control group. During the study period, the number of deliveries was approximately 110,000. Of these, 33 women with liver cirrhosis were identified, yielding an estimated frequency of cirrhosis of 1 per 3,333 pregnancies [95% confidence interval (CI) 3,313-3,353]. Thirty-one of these 33 women met all inclusion criteria. The most common etiology of cirrhosis was alcoholic liver disease. The rate of the primary outcome was 61% in women with cirrhosis and 12% in women in the control group. There were no cases of maternal death, and the livebirth rate was 97%. Women with cirrhosis were more likely to be non-Hispanic black, have chronic hypertension, and use alcohol. Multivariable logistic regression demonstrated that cirrhosis in pregnancy was associated with the composite outcome (adjusted odds ratio 9.4, 95% CI 3.4-26.2). Despite lower rates of maternal and fetal mortality compared with earlier studies, pregnancy in women with liver cirrhosis is still associated with a high risk of adverse obstetric outcomes.

Mediating mechanisms of a military Web-based alcohol intervention.

PubMed

Williams, Jason; Herman-Stahl, Mindy; Calvin, Sara L; Pemberton, Michael; Bradshaw, Michael

2009-03-01

This study explored the mediating mechanisms of two Web-based alcohol interventions in a sample of active duty United States military personnel. Personnel were recruited from eight bases and received the Drinker's Check-Up (N=1483), Alcohol Savvy (N=688), or served as controls (N=919). The interventions drew on motivational interviewing and social learning theory and targeted multiple mediators including social norms, perceived risks and benefits, readiness to change, and coping strategies. Baseline data were collected prior to the intervention and follow-up data on alcohol consumption were gathered 1 month and 6 months after program completion. Two mediation models were examined: (1) a longitudinal two-wave model with outcomes and mediators assessed concurrently at the 1-month follow-up; and (2) a three-wave model in which the causal chain was fully lagged. Results indicated strong support for the role of perceived descriptive norms in transmitting the effects of the Drinker's Check-Up, with consistent mediation across the majority of alcohol outcome measures for both the concurrent and fully lagged mediation models. These results suggest that web-based interventions that are effective in lowering perceived norms about the frequency and quantity of drinking may be a viable strategy for reducing alcohol consumption in military populations. The results did not support program mediation by the other targeted variables, indicating the need for future research on the effective components of alcohol interventions. The mediation models also suggest reasons why program effects were not found for some outcomes or were different across programs.

Chronic Hepatitis C-Related Cirrhosis Hospitalization Cost Analysis in Bulgaria.

PubMed

Dimitrova, Maria; Pavlov, Kaloyan; Mitov, Konstantin; Genov, Jordan; Petrova, Guenka Ivanova

2017-01-01

HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014). It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing. 76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score. HCV-related cirrhosis is resource demanding and sets high

New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases

PubMed Central

Williams, Jessica A; Manley, Sharon; Ding, Wen-Xing

2014-01-01

Alcoholic liver disease is a major health problem in the United States and worldwide. Chronic alcohol consumption can cause steatosis, inflammation, fibrosis, cirrhosis and even liver cancer. Significant progress has been made to understand key events and molecular players for the onset and progression of alcoholic liver disease from both experimental and clinical alcohol studies. No successful treatments are currently available for treating alcoholic liver disease; therefore, development of novel pathophysiological-targeted therapies is urgently needed. This review summarizes the recent progress on animal models used to study alcoholic liver disease and the detrimental factors that contribute to alcoholic liver disease pathogenesis including miRNAs, S-adenosylmethionine, Zinc deficiency, cytosolic lipin-1β, IRF3-mediated apoptosis, RIP3-mediated necrosis and hepcidin. In addition, we summarize emerging adaptive protective effects induced by alcohol to attenuate alcohol-induced liver pathogenesis including FoxO3, IL-22, autophagy and nuclear lipin-1α. PMID:25278688

Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis

PubMed Central

Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-hua; Xue, Dongbo

2017-01-01

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma. PMID:28355233

Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.

PubMed

Gao, Bo; Zhang, Xueming; Huang, Yongming; Yang, Zhengpeng; Zhang, Yuguo; Zhang, Weihui; Gao, Zu-Hua; Xue, Dongbo

2017-01-01

Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including "immune response" as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.

Testing Mediators of Reduced Drinking for Veterans in Alcohol Care Management.

PubMed

Moskal, Dezarie; Maisto, Stephen A; Possemato, Kyle; Lynch, Kevin G; Oslin, David W

2018-03-26

Alcohol Care Management (ACM) is a manualized treatment provided by behavioral health providers working in a primary care team aimed at increasing patients' treatment engagement and decreasing their alcohol use. Research has shown that ACM is effective in reducing alcohol consumption; however, the mechanisms of ACM are unknown. Therefore, the purpose of this study is to examine the mechanisms of change in ACM in the context of a randomized clinical trial evaluating the effectiveness of ACM. This study performed secondary data analysis of existing data from a larger study that involved a sample of U.S. veterans (N = 163) who met criteria for current alcohol dependence. Upon enrollment into the study, participants were randomized to receive either ACM or standard care. ACM was delivered in-person or by telephone within the primary care clinic and focused on the use of oral naltrexone and manualized psychosocial support. According to theory, we hypothesized several ACM treatment components that would mediate alcohol consumption outcomes: engagement in addiction treatment, reduced craving, and increased readiness to change. Parallel mediation models were performed by the PROCESS macro Model 4 in SPSS to test study hypotheses. The institutional review boards at each of the participating facilities approved all study procedures before data collection. As hypothesized, results showed that treatment engagement mediated the relation between treatment and both measures of alcohol consumption outcomes, the percentage of alcohol abstinent days, and the percentage of heavy drinking days. Neither craving nor readiness to change mediated the treatment effect on either alcohol consumption outcome. Findings suggest that ACM may be effective in changing drinking patterns partially due to an increase in treatment engagement. Future research may benefit from evaluating the specific factors that underlie increased treatment engagement. The current study provides evidence that alcohol

Bullying perpetration and victimization as externalizing and internalizing pathways: A retrospective study linking parenting styles and self-esteem to depression, alcohol use, and alcohol-related problems

PubMed Central

Patock-Peckham, Julie A; Medina, Mia; Terrell, Nathan; Belton, Daniel; King, Kevin M

2016-01-01

Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use and alcohol-related problems. Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique in structural equation modeling. Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Results suggested that bullying perpetration and victimization may respectively serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use. PMID:26757486

Bullying Perpetration and Victimization as Externalizing and Internalizing Pathways: A Retrospective Study Linking Parenting Styles and Self-Esteem to Depression, Alcohol Use, and Alcohol-Related Problems.

PubMed

Luk, Jeremy W; Patock-Peckham, Julie A; Medina, Mia; Terrell, Nathan; Belton, Daniel; King, Kevin M

2016-01-02

Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use, and alcohol-related problems. Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique within a structural equation modeling framework. Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn, was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Results suggested that bullying perpetration and victimization may, respectively, serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use.

Gut microbiota-related complications in cirrhosis

PubMed Central

Gómez-Hurtado, Isabel; Such, José; Sanz, Yolanda; Francés, Rubén

2014-01-01

Gut microbiota plays an important role in cirrhosis. The liver is constantly challenged with commensal bacteria and their products arriving through the portal vein in the so-called gut-liver axis. Bacterial translocation from the intestinal lumen through the intestinal wall and to mesenteric lymph nodes is facilitated by intestinal bacterial overgrowth, impairment in the permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences. Deranged clearance of endogenous bacteria from portal and systemic circulation turns the gut into the major source of bacterial-related complications. Liver function may therefore be affected by alterations in the composition of the intestinal microbiota and a role for commensal flora has been evidenced in the pathogenesis of several complications arising in end-stage liver disease such as hepatic encephalopathy, splanchnic arterial vasodilatation and spontaneous bacterial peritonitis. The use of antibiotics is the main therapeutic pipeline in the management of these bacteria-related complications. However, other strategies aimed at preserving intestinal homeostasis through the use of pre-, pro- or symbiotic formulations are being studied in the last years. In this review, the role of intestinal microbiota in the development of the most frequent complications arising in cirrhosis and the different clinical and experimental studies conducted to prevent or improve these complications by modifying the gut microbiota composition are summarized. PMID:25400446

Effects of Treatment Type on Alcohol Consumption Partially Mediated by Alcoholics Anonymous Attendance.

PubMed

Karriker-Jaffe, Katherine J; Klinger, Jamie L; Witbrodt, Jane; Kaskutas, Lee Ann

2018-03-21

As insurance coverage, funding sources and venues for drug and alcohol treatment evolve in the United States, it is important to assess how the type of treatment received may impact long-term outcomes. The current study aims were to examine effects of treatment type on alcohol consumption in the year after treatment intake and to test mediators of effects of treatment type on later alcohol use. Longitudinal data from clients in inpatient and outpatient alcohol treatment programs in California (n = 560) were used in ordinary least squares path analysis adjusting for respondent characteristics typically associated with both treatment completion and alcohol use. The primary outcome was amount of alcohol consumed in the 12 months after treatment entry; hypothesized mediators were treatment duration and participation in Alcoholics Anonymous (AA). Despite higher baseline problem severity and a shorter treatment duration, inpatient clients consumed less alcohol after treatment than outpatient clients (B [95% CI] = -0.95 [-1.67, -0.23]). AA involvement was a significant mediator of the relationship between treatment type and alcohol consumption, with inpatient clients being more involved in AA and also drinking less after treatment than outpatient clients; the bias-corrected bootstrap 95% confidence interval for the indirect effect (B = -0.20) was entirely below zero (-0.43 to -0.05). Outpatient clients may benefit from customized posttreatment recommendations to identify additional resources to assist in the recovery process during the first year after treatment.

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

PubMed Central

GAO, BIN; BATALLER, RAMON

2011-01-01

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide and can lead to fibrosis and cirrhosis. The latest surveillance report published by the National Institute on Alcohol Abuse and Alcoholism showed that liver cirrhosis was the 12th leading cause of death in the United States, with a total of 29,925 deaths in 2007, 48% of which were alcohol related. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Early work on the pathogenesis of the disease focused on ethanol metabolism–associated oxidative stress and glutathione depletion, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. We review findings from recent studies that have characterized specific intracellular signaling pathways, transcriptional factors, aspects of innate immunity, chemokines, epigenetic features, microRNAs, and stem cells that are associated with ALD, improving our understanding of its pathogenesis. Despite this progress, no targeted therapies are available. The cornerstone of treatment for alcoholic hepatitis remains as it was 40 years ago: abstinence, nutritional support, and corticosteroids. There is an urgent need to develop new pathophysiology-oriented therapies. Recent translational studies of human samples and animal models have identified promising therapeutic targets. PMID:21920463

Liver cirrhosis in Malaysia: peculiar epidemiology in a multiracial Asian country.

PubMed

Qua, Choon-Seng; Goh, Khean-Lee

2011-08-01

To determine the etiology of liver cirrhosis and risk factors for hepatocellular carcinoma (HCC) in a multiracial Asian population. Consecutive patients with liver cirrhosis presenting to outpatient clinics and inpatient service at the University of Malaya Medical Centre from 1 April 2006 to 31 May 2009 were included. A total of 460 patients were included in the study: 317 male patients (68.9%) and 143 female patients (31.1%), with a mean age of 58.8years (range: 15-87years). The major causes of cirrhosis were: chronic hepatitis B, n=212, 46.1%; chronic hepatitis C, n=85, 18.5%; cryptogenic, n=71, 15.4%; alcohol, n=58, 12.6% and autoimmune, n=9, 2.0%. Alcohol was the main etiology in Indians (51.1%) compared to Malay (0%) and Chinese (4.4%) (both P<0.001). Hepatitis B was the predominant etiology in Malay (47.9%) and Chinese (58.8%) compared to Indians (5.6%) (both P<0.001). Hepatitis C cirrhosis was highest in Malays (25.0%). 136 patients (29.6%) had concurrent HCC. Male sex (P<0.001), age>60years (P=0.014), hepatitis B (P<0.001), hepatitis C (P=0.006) and cryptogenic cause (P=0.002) were found to be independent risk factors for HCC. The etiology of cirrhosis has a peculiar pattern based on racial differences in alcohol intake and in the prevalence of hepatitis B. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis.

PubMed

Tellez-Avila, Felix I; Sanchez-Avila, Francisco; García-Saenz-de-Sicilia, Mauricio; Chavez-Tapia, Norberto C; Franco-Guzman, Ada M; Lopez-Arce, Gustavo; Cerda-Contreras, Eduardo; Uribe, Misael

2008-08-14

To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls). Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis (AIH) served as disease controls. A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The prevalence of MS (29.1% vs 6%; P<0.001), obesity (16.4% vs 8.2%; P=0.04) and T2DM (40% vs 22.4%; P=0.013) was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. The prevalence of MS, obesity and T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC.

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease.

PubMed

Jensen, Thomas; Abdelmalek, Manal F; Sullivan, Shelby; Nadeau, Kristen J; Green, Melanie; Roncal, Carlos; Nakagawa, Takahiko; Kuwabara, Masanari; Sato, Yuka; Kang, Duk-Hee; Tolan, Dean R; Sanchez-Lozada, Laura G; Rosen, Hugo R; Lanaspa, Miguel A; Diehl, Anna Mae; Johnson, Richard J

2018-05-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup [HFCS]) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Mindfulness as a mediator of the association between adverse childhood experiences and alcohol use and consequences.

PubMed

Brett, Emma I; Espeleta, Hannah C; Lopez, Susanna V; Leavens, Eleanor L S; Leffingwell, Thad R

2018-09-01

One-third of college students report past-year heavy episodic drinking, making college student alcohol use an important area for continued research. Research has consistently linked early experiences of adversity to problematic substance use in adolescence and adulthood. Given the negative health consequences associated with heavy episodic drinking, it is imperative to identify mechanisms that contribute to this relation. Low levels of mindfulness have been linked to early adversity as well as impulsivity and alcohol use, therefore, the current study aims to examine the mediating role of mindfulness in the relation between early adversity and current alcohol use and consequences. Undergraduate students (N = 385) at a Midwestern university completed an online questionnaire assessing experiences of childhood adversity, trait mindfulness, and current alcohol use and related consequences. Results indicated that increased adverse experiences and lower levels of mindfulness predicted both increased alcohol consumption and consequences (ps < 0.025), with mindfulness mediating the relationships. Mindfulness is a predictor of alcohol outcomes and appears to mediate the relation between early adversity and alcohol use and consequences. Findings suggest that students with a history of adversity are more likely to exhibit lower levels of mindfulness, which may lead to an increase in alcohol consumption and consequences in early adulthood. Targeted alcohol intervention efforts that incorporate mindfulness skills may be particularly beneficial for those who have experienced early adversity. Copyright © 2018. Published by Elsevier Ltd.

Effect of fluoroquinolone on the enhanced nitric oxide-induced peripheral vasodilation seen in cirrhosis.

PubMed

Chin-Dusting, J P; Rasaratnam, B; Jennings, G L; Dudley, F J

1997-12-01

In patients with cirrhosis, portosystemic shunts allow intestinal bacteria and endotoxin to enter the systemic circulation. Endotoxemia may induce increased synthesis of nitric oxide, thereby contributing to arterial vasodilation. To test the hypothesis that the antibiotic norfloxacin blocks the effects of nitric oxide. Placebo-controlled, double-blind, crossover study. Alfred Hospital, Melbourne, Australia. 9 patients with alcohol-related cirrhosis and 10 healthy controls. Norfloxacin, 400 mg twice daily, for 4 weeks. Peripheral blood flow was measured by using forearm venous occlusion plethysmography. Basal forearm blood flow was higher in patients with cirrhosis than in controls (3.69 +/- 0.27 mL/100 mL per minute and 2.47 +/- 0.40 mL/100 mL per minute; P = 0.014) but returned toward normal after norfloxacin was given (2.64 +/- 0.31 mL/100 mL of tissue per minute in patients with cirrhosis). Responses to NG-monomethyl-L-arginine were greater in patients with cirrhosis but returned to normal after norfloxacin was given. Bacterial endotoxemia in patients with cirrhosis induces increased synthesis of nitric oxide that can be corrected with norfloxacin.

Analysis of Serum Haptoglobin Fucosylation in Hepatocellular Carcinoma and Liver Cirrhosis of Different Etiologies

PubMed Central

2015-01-01

We have developed herein a quantitative mass spectrometry-based approach to analyze the etiology-related alterations in fucosylation degree of serum haptoglobin in patients with liver cirrhosis and hepatocellular carcinoma (HCC). The three most common etiologies, including infection with hepatitis B virus (HBV), infection with hepatitis C virus (HCV), and heavy alcohol consumption (ALC), were investigated. Only 10 μL of serum was used in this assay in which haptoglobin was immunoprecipitated using a monoclonal antibody. The N-glycans of haptoglobin were released with PNGase F, desialylated, and permethylated prior to MALDI-QIT-TOF MS analysis. In total, N-glycan profiles derived from 104 individual patient samples were quantified (14 healthy controls, 40 cirrhosis, and 50 HCCs). A unique pattern of bifucosylated tetra-antennary glycan, with both core and antennary fucosylation, was identified in HCC patients. Quantitative analysis indicated that the increased fucosylation degree was highly associated with HBV- and ALC-related HCC patients compared to that of the corresponding cirrhosis patients. Notably, the bifucosylation degree was distinctly increased in HCC patients versus that in cirrhosis of all etiologies. The elevated bifucosylation degree of haptoglobin can discriminate early stage HCC patients from cirrhosis in each etiologic category, which may be used to provide a potential marker for early detection and to predict HCC in patients with cirrhosis. PMID:24807840

Association between complicated liver cirrhosis and the risk of hepatocellular carcinoma in Taiwan.

PubMed

Hung, Tsung-Hsing; Liang, Chih-Ming; Hsu, Chien-Ning; Tai, Wei-Chen; Tsai, Kai-Lung; Ku, Ming-Kun; Wang, Jiunn-Wei; Tseng, Kuo-Lun; Yuan, Lan-Ting; Nguang, Seng-Howe; Yang, Shih-Cheng; Wu, Cheng-Kun; Hsu, Pin-I; Wu, Deng-Chyang; Chuah, Seng-Kee

2017-01-01

Hepatic encephalopathy, ascites, and variceal bleeding are the three major complications of cirrhosis. It is well known that cirrhosis is the most important risk factor of hepatocellular carcinoma (HCC). However, little is known about whether the severity of liver cirrhosis has an effect on the incidence of HCC. This population-based cohort study aimed to explore the association between complicated cirrhosis and HCC, and identify the risk factors of HCC in patients with complicated cirrhosis. Data of the years 1997-2011 were extracted from the National Health Insurance Research Database of Taiwan. A total of 2568 patients with complicated cirrhosis without HCC at baseline were enrolled. After propensity score matching, another 2568 patients with non-complicated cirrhosis were included. Hazards Cox regression analysis by using a competing risk regression model to control for possible confounding factors was utilized to estimate the association of the complications of liver cirrhosis with the risk of HCC. We observed by using competing risk analysis that the adjusted hazard ratio (HR) for developing HCC during the follow-up period after the initial hospitalization was higher among the patients with baseline complicated cirrhosis than in those with uncomplicated cirrhosis (HR, 1.23; 95% confidence interval, CI, 1.10-1.37, p<0.001). Additionally, older patients (HR, 1.01; 95% CI, 1.01-1.02, p<0.001), males (HR, 0.84; 95% CI, 0.74-0.96, p = 0.009), and patients with alcohol-related cirrhosis (HR, 1.93; 95% CI, 1.65-2.26, p<0.001) had a statistically significant difference in the incidence of HCC. In conclusion, complicated liver cirrhosis is associated with a higher risk of HCC in Taiwan compared with cirrhosis without complications.

Presence and consequence of tooth periapical radiolucency in patients with cirrhosis

PubMed Central

Grønkjær, Lea Ladegaard; Holmstrup, Palle; Schou, Søren; Schwartz, Kristoffer; Kongstad, Johanne; Jepsen, Peter; Vilstrup, Hendrik

2016-01-01

Background Periapical radiolucency is the radiographic sign of inflammatory bone lesions around the apex of the tooth. We determined the prevalence and predictors of periapical radiolucency in patients with cirrhosis and the association with systemic inflammation status and cirrhosis-related complications. Methods A total of 110 cirrhosis patients were consecutively enrolled. Periapical radiolucency was defined as the presence of radiolucency or widening of the periapical periodontal ligament space to more than twice the normal width. Predictors of periapical radiolucency and the association with systemic inflammation markers and cirrhosis-related complications were explored by univariable and multivariable logistic regression analyses. Results Periapical radiolucency was present in one or more teeth in 46% of the patients. Strong predictors were gross caries (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.43–6.79) and severe periodontitis (OR 3.98, 95% CI 1.04–15.20). Also old age (OR 1.10, 95% CI 1.01–1.19) and smoking (OR 3.24, 95% CI 1.02–17.62) were predictors. However, cirrhosis etiology (alcoholic vs nonalcoholic) or severity (Model of End-Stage Liver Disease score) were not predictors. The patients with periapical radiolucency had higher C-reactive protein (15.8 mg/L vs 8.1 mg/L, P=0.02) and lower albumin contents (25 g/L vs 28 g/L, P=0.04) than those without. Furthermore, the patients with periapical radiolucency had a higher prevalence of cirrhosis-related complications such as ascites, hepatic encephalopathy, and/or variceal bleeding (46% vs 27%, P=0.05). Conclusion Periapical radiolucency is often present as an element of poor oral health status and likely has an adverse clinical significance, which should motivate diagnostic and clinical attention to the findings. PMID:27695370

Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes.

PubMed

Beulens, Joline W J; van der Schouw, Yvonne T; Moons, Karel G M; Boshuizen, Hendriek C; van der A, Daphne L; Groenwold, Rolf H H

2013-04-01

Moderate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol-biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown. In a case-cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method. Using the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41-243), whereas high-sensitivity C-reactive protein (-7.5%; -36.4 to 1.8) or blood pressure (-6.9; -26.3 to -0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower. The relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure-mediator interactions may result in bias. The difference and G-estimation methods provide similar results. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of birth cohorts in long-term trends in liver cirrhosis mortality across eight European countries.

PubMed

Trias-Llimós, Sergi; Bijlsma, Maarten J; Janssen, Fanny

2017-02-01

Understanding why inequalities in alcohol-related mortality trends by sex and country exist is essential for developing health policies. Birth cohort effects, indicative of differences by generation in drinking, have rarely been studied. This study estimated the relative contributions of birth cohorts to liver cirrhosis mortality trends and compared sex- and country-specific cohort patterns across eight European countries. Time-series analysis of population-level mortality data. Austria, Finland, Hungary, Italy, the Netherlands, Poland, Spain and Sweden; 1950-2011. National populations aged 15-94 years. We modelled country- and sex-specific liver cirrhosis mortality (from national vital registers) adjusting for age, period and birth cohort. Birth cohorts (adjusted for age and period) made statistically significant contributions to liver cirrhosis mortality in all countries and for both sexes (P < 0.001), and more so among women (average contribution to deviance reduction of 38.8%) than among men (17.4%). The observed cohort patterns were statistically different between all but two country pairs (P < 0.001). Sex differences existed overall (P < 0.001), but not in the majority of countries (P > 0.999). Visual inspection of birth cohort patterns reveals birth cohorts at higher risk of liver cirrhosis mortality. The inclusion of the birth cohort dimension improves the understanding of alcohol-attributable mortality trends in Europe. Birth cohorts at higher risk of liver cirrhosis mortality were born during 1935-49 in Sweden and Finland, around 1950 in Austria and the Netherlands and 1960 or later in Hungary, Italy, Poland and Spain. © 2016 Society for the Study of Addiction.

[Prophylaxis of alcoholic disease of the liver].

PubMed

Beliakin, S A

2009-08-01

Military doctors should have a uniform position to the use of alcohol. Now alcohol is the basic pathogenic factor in development of a lethal cirrhosis of a liver. The most known sayings justifying the use of alcohol, are insolvent. Useful doses of alcohol does not exist. The quantity of used alcohol has the great value. Only at achievement of age 21 year it is possible to use safe doses of alcohol. A safe dose of pure alcohol (ethanol) less than 30,0 in day. In a basis of prophylaxis of a cirrhosis of a liver there is a medical educational activity.

Diagnosis and Management of Alcoholic Liver Disease.

PubMed

Dugum, Mohannad; McCullough, Arthur

2015-06-28

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

College drinking behaviors: mediational links between parenting styles, parental bonds, depression, and alcohol problems.

PubMed

Patock-Peckham, Julie A; Morgan-Lopez, Antonio A

2007-09-01

Mediational links between parenting styles (authoritative, authoritarian, permissive), parental bond (positive, negative), depression, alcohol use and abuse were tested. A 2-group, multiple-indicator, multiple-cause structural equation model with 441 (216 female, 225 male) college students was examined. In general, a poor parental bond with one's father was highly predictive of depression, a well-known predictor of alcohol abuse and related problems for both genders. In contrast, a positive parental bond with one's father significantly mediated the positive effects of authoritative fathering on depression, which then decreased alcohol use problems for both genders. For women, a negative parental bond with one's father significantly mediated the effect of having an authoritarian father on depression, which increased alcohol use problems. These findings suggest that parental influences on pathways to alcohol abuse through depression (primarily through fathers for both genders) are distinct from pathways stemming from poor impulse control (with influences primarily from the same-sex parents for both genders).

Risk factors for hepatocellular carcinoma in Caucasian patients with non-viral cirrhosis: the importance of prior obesity.

PubMed

Archambeaud, Isabelle; Auble, Hélène; Nahon, Pierre; Planche, Lucie; Fallot, Guillaume; Faroux, Roger; Gournay, Jérôme; Samuel, Didier; Kury, Sebastien; Féray, Cyrille

2015-07-01

In patients with cirrhosis, the risk of hepatocellular carcinoma (HCC) depends upon age, gender and the etiology of liver disease. Few studies are available in Caucasian patients with alcoholic or metabolic cirrhosis without viral hepatitis. Cross-sectional clinical data from 905 HCV- and HBV-negative Caucasian patients with alcoholic or metabolic cirrhosis were prospectively collected in four French centres. The risk factors for HCC were identified by logistic regression analysis in the whole population and in a nested case-control study. The etiology of cirrhosis was alcoholic (48%), metabolic (7%) or mixed (45%). Patients were predominantly male (80%), mean age 62 years old and 31% had HCC. Mean body mass index (BMI) was 27 ± 5 and 30% were obese at inclusion. The maximum BMI reached throughout life was 31 ± 6 and 63% had been obese. Ninety percent of the population had daily alcohol consumption, 73% were smokers. Hepatocellular carcinoma was independently related to male gender (P < 0.0001), older age (P < 0.0001), past obesity (P = 0.007), diabetes (P = 0.037), abnormal levels of transaminases (P < 0.0001) and tobacco consumption (P = 0.007). The case-control study (200 HCC cases matched with 400 non-HCC cases for gender, age and Child-Pugh score) confirmed past obesity, tobacco and abnormal levels of transaminases. Beside diabetes, male gender and age, a past history of obesity, but not an existing overweight, as well as exposure to tobacco and elevated transaminases were three risk factors which could improve the strategy for HCC screening in Caucasian cirrhotic patients without hepatitis B or C. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Watching and drinking: Expectancies, prototypes, and peer affiliations mediate the effect of exposure to alcohol use in movies on adolescent drinking

PubMed Central

Dal Cin, Sonya; Worth, Keilah A.; Gerrard, Meg; Gibbons, Frederick X.; Stoolmiller, Mike; Wills, Thomas A.; Sargent, James D.

2009-01-01

Objective To investigate the psychological processes that underlie the relation between exposure to alcohol use in media with adolescent alcohol use. Design Structural equation modeling analysis of data from four waves of a longitudinal, nationally-representative, random-digit dial telephone survey of adolescents in the United States. Main Outcome Measures Adolescent alcohol consumption and willingness to use alcohol. Tested mediators were alcohol-related norms, prototypes, expectancies, and friends' use. Results Alcohol prototypes, expectancies, willingness, and friends' use of alcohol (but not perceived prevalence of alcohol use among peers) were significant mediators of the relation between movie alcohol exposure and alcohol consumption, even after controlling for demographic, child, and family factors associated with both movie exposure and alcohol consumption. Conclusion Established psychological and interpersonal predictors of alcohol use mediate the effects of exposure to alcohol use in movies on adolescent alcohol consumption. The findings suggest that exposure movie portrayals may operate through similar processes as other social influences, highlighting the importance of considering these exposures in research on adolescent risk behavior. PMID:19594272

[Experience in the treatment of some complications of portal hypertension in alcoholic liver cirrhosis].

PubMed

Savić, Zeljka; Vracarić, Vladimir; Hadnadjev, Ljiljana; Petrović, Zora; Damjanov, Dragomir

2011-11-01

Portal hypertension (PH) is hemodynamical abnormality associated with the most serious complications of alcoholic liver cirrhosis (ALC): ascites, varices and variceal bleeding. The aim of this study was to determine characteristics of portal hypertension, especially of upper gastrointestinal bleedings in patients with alcoholic liver cirrhosis (ALC). A total of 237 patients with ALC were observed in a 3-year period. A total of 161 patients (68%) were hospitalized because of PH elements: 86 (36.3%) had upper gastrointestinal bleeding, 75 (31.7%) were decompensated. Only 76 (32%) of the patients had icterus. General mortality was 85 (36%). According to the source of bleeding, 61 (71%) patients bled from varices, and 25 (29%) from other sources with existing varices but non-incriminated for bleeding in 16 (64%) of those patients. Active bleeding or stigmata of recent bleeding were found in 63 (73%) cases. Endoscopic treatment of variceal bleeding along with octreotide applied in 20 (32.78%) patients, just octreotide in 32 (52.46%), and octreotid plus balloon tamponade in 9 (14.75%). According to Child-Pugh classification, 25 (29%) of the bleeding patients were in class A, score 5.4; 43 (50%) in class B, score 7.8; and 18 (21%) in class C, score 10.9. Average hemoglobin level was 93 g/L, hematocrit 0.27, AST 71.52 U/L (normal to 37 U/L), ALT 37.74 U/L (normal to 40 U/L). Until this bleeding episode, 41 (47%) of the patients already bled. In the decompensated patients 3 (4%) were in Child Pugh class A, score 6; 42 (56%) in class B, score 8.3; and 30 (40%) in class C, score 10.6. Until this decompensation episode, 7 (9.3%) patients already bled. Patients with ALC need early detection of varices, primary and secondary profilaxis of variceal bleeding and adequate therapy of ascites. When bleeding occurs, patients need urgent upper endoscopy and intensive treatment.

Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort.

PubMed

Setiawan, Veronica Wendy; Stram, Daniel O; Porcel, Jacqueline; Lu, Shelly C; Le Marchand, Loïc; Noureddin, Mazen

2016-12-01

Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%). We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969-1977). © 2016 by the American Association for the Study of Liver Diseases.

Religiousness and Alcohol Use in College Students: Examining Descriptive Drinking Norms as Mediators

ERIC Educational Resources Information Center

Brechting, Emily H.; Carlson, Charles R.

2015-01-01

Religiousness has consistently emerged in the literature as a protective factor for alcohol use. Relatively few studies have empirically explored possible mechanisms for this robust effect. The present study examines descriptive drinking norms as a potential mediator of the religiousness--alcohol consumption association. Consistent with the…

In patients with liver cirrhosis, proinflammatory interleukins correlate with health-related quality of life irrespective of minimal hepatic encephalopathy.

PubMed

Wunsch, Ewa; Koziarska, Dorota; Milkiewicz, Małgorzata; Naprawa, Grzegorz; Nowacki, Przemysław; Hartleb, Marek; Milkiewicz, Piotr

2013-12-01

Liver cirrhosis is associated with latent systemic inflammatory response syndrome as evidenced by elevated levels of proinflammatory cytokines. It has been proposed that inflammatory mediators play a role in the pathogenesis of minimal and overt hepatic encephalopathy (HE); hence, they may also have an effect on health-related quality of life (HRQL). The aim of this study was to investigate the relationship between serum levels of interleukin-1β (IL-1β), IL-6, and IL-18 and the occurrence of minimal HE and HRQL. Forty-two consecutive patients with liver cirrhosis were prospectively enrolled to the study. Minimal HE was detected by the Psychometric Hepatic Encephalopathy Score (PHES) and critical flicker frequency. HRQL was assessed with Chronic Liver Disease Questionnaire and 36-Item Short Form Health Survey (SF-36) questionnaires. The interleukins studied were determined using colorimetric sandwich enzyme-linked immunosorbent assay. Serum levels of interleukins correlated with liver dysfunction, but did not discriminate patients with minimal HE from those with overt or absent HE. IL-1β and IL-6 showed significant correlations with PHES, but showed no relationship with critical flicker frequency. Serum IL-6 and IL-18 correlated with both physical-related general health and mental component summary evaluated by the SF-36 questionnaire. This study shows that chronic inflammation plays a role in impaired HRQL in patients with cirrhosis irrespective of minimal HE.

Study of liver cirrhosis over ten consecutive years in Southern China.

PubMed

Wang, Xing; Lin, Shang-Xiong; Tao, Jin; Wei, Xiu-Qing; Liu, Yuan-Ting; Chen, Yu-Ming; Wu, Bin

2014-10-07

2006-2010, the proportion of viral hepatitis decreased from 84.7% to 78.3% (P < 0.001), and the proportion of HBV-induced LC also decreased from 81.9% to 74.6% (P < 0.001). The incidence of mixed etiology, cryptogenic cirrhosis, and autoimmune diseases increased by 3.1% (P < 0.001), 0.5% (P = 0.158), and 1.3% (P < 0.001), respectively. Alcohol-induced LC remained relatively steady over the 10-year period. The ORs of the development of UGIB between HBV and other major etiologies were as follows: HCV, 1.07; alcohol, 1.89; autoimmune, 0.90; mixed etiology, 0.83; and cryptogenic, 1.76. The ORs of the occurrence of HCC between HBV and other major etiologies were as follows: HCV, 0.54; alcohol, 0.16; autoimmune, 0.05; mixed etiology, 0.58; and cryptogenic, 0.60. The major etiology of liver cirrhosis in Southern China is viral hepatitis. However, the proportions of viral hepatitis and HBV are gradually decreasing. Alcoholic LC patients exhibit a greater risk of experiencing UGIB, and HBV LC patients may have a greater risk of HCC.

Incidence, survival and cause-specific mortality in alcoholic liver disease: a population-based cohort study.

PubMed

Sahlman, Perttu; Nissinen, Markku; Pukkala, Eero; Färkkilä, Martti

2016-08-01

We studied the incidence of severe ALD requiring hospitalization in Finland, and survival and causes of death among the ALD patients. A cohort of 11,873 persons (8796 men and 3077 women) with diagnosis of ALD during the years 1996-2012 was identified from Finnish national Inpatient Register. The annual incidence of alcoholic hepatitis (AH) and alcoholic liver cirrhosis was calculated. The cohort was combined with the data from national Cause of Death Register of Statistics Finland. The incidence of alcoholic liver cirrhosis increased from 8.8/100,000 in year 2001 to 14.6/100,000 in year 2012 among men and from 2.4 to 4.2/100,000 among women. The incidence of AH increased from 3.7 to 6.5/100,000 among men and from 1.3 to 2.7/100,000 among women. The relative 5-year survival ratios of patients with alcoholic liver cirrhosis and AH were 29 and 50% among men and 38 and 52% among women, respectively. Out of 8440 deaths, 65% were due to alcoholic-related causes. The risk of death among ALD patients was increased in malignancies (SMR 6.82; 95% CI: 6.35-7.29), cardiovascular diseases (6.13; 5.74-6.52), respiratory diseases (7.86; 6.70-9.10), dementia (3.31; 2.41-4.44) and accidents and violence (11.12; 10.13-12.15). The incidence of AH and alcoholic liver cirrhosis is increasing. The survival is poor. Most deaths are alcohol-related and other common causes of excess deaths are cancers especially in the upper aerodigestive tract and cardiovascular, digestive and respiratory diseases as well as violence and accidents.

Mechanisms and cell signaling in alcoholic liver disease

PubMed Central

Beier, Juliane I.; McClain, Craig J.

2013-01-01

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of ALD, rational targeted therapy can be developed to treat or prevent ALD. The purpose of this review is to summarize the established and proposed mechanisms by which chronic alcohol abuse damages the liver and to highlight key signaling events known or hypothesized to mediate these effects. PMID:20868231

Genetic moderators and psychiatric mediators of the link between sexual abuse and alcohol dependence.

PubMed

Copeland, William E; Magnusson, Asa; Göransson, Mona; Heilig, Markus A

2011-06-01

This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that might affect treatment planning. A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Genetic Moderators and Psychiatric Mediators of the link between Sexual Abuse and Alcohol Dependence

PubMed Central

Copeland, William E.; Magnusson, Åsa; Göransson, Mona; Heilig, Markus A.

2011-01-01

Background/Objective This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that that might affect treatment planning. Methods A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. Results The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Conclusion Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. PMID:21193270

Does alcohol craving mediate the impulsivity-aggression relationship in recently detoxified alcohol-dependent patients?

PubMed

Roozen, H G; Wetering, B J M van de; Franken, I H A

2013-01-01

The relationship between the use of alcohol and aggression is complex and represents major public health issues. Delving into the nature of this association is vital, since various underlying factors may contribute to the expression of aggression. This study examined trait aggression by assessing correlates and, subsequently, the unique contribution of alcohol craving, and dysfunctional impulsivity, by means of correlational and mediational analyses. Forty inpatient detoxified alcohol-dependent patients were recruited. These participants completed the Desire for Alcohol Questionnaire (DAQ), Dickman Impulsivity Inventory (DII), and the Aggression Questionnaire (AQ). The findings indicated that aggression, dysfunctional impulsivity, and alcohol craving were all positively intercorrelated. The association between dysfunctional impulsivity and aggression was robust. The mediational analyses yielded that craving partially mediated this relationship, although not very substantial. It was shown that impulsivity, as a personality characteristic, is strongly associated with aggressive behaviors, whereby the impact of craving on the relationship between impulsivity and trait aggression in alcohol-dependent inpatients was weak. Since it has been posited that factors such as impulsivity and craving may contribute to the lucid association between substance use and aggression, these findings mirror previous research on stimulant users and, subsequently, substantiates that craving exerts only a minor weight on the strong impulsivity-aggression relationship.

Traumatic stress and the mediating role of alcohol use on HIV-related sexual risk behavior: results from a longitudinal cohort of South African women who attend alcohol-serving venues.

PubMed

Abler, Laurie; Sikkema, Kathleen J; Watt, Melissa H; Pitpitan, Eileen V; Kalichman, Seth C; Skinner, Donald; Pieterse, Desiree

2015-03-01

In South Africa, alcohol contributes to the HIV epidemic, in part, by influencing sexual behaviors. For some, high levels of alcohol consumption may be driven by previous traumatic experiences that result in traumatic stress. The purpose of this study was to quantify the longitudinal association between traumatic stress and unprotected sex among women who attend drinking venues and to assess whether this association was explained by mediation through alcohol use. Data were collected in 4 waves over a year from a prospective cohort of 560 women who regularly attended alcohol-serving venues in a Cape Town township. Longitudinal mixed models examined (1) the relationship between traumatic stress and counts of unprotected sex and (2) whether alcohol use mediated the association between traumatic stress and unprotected sex. Most women reported elevated traumatic stress (80%) and hazardous alcohol use (88%) at least once during the study period. In models adjusted for covariates, traumatic stress was associated with unprotected sex (b = 0.28, SE = 0.06, t = 4.82, P < 0.001). In addition, traumatic stress was associated with alcohol use (b = 0.27, SE = 0.02, t = 14.25, P < 0.001) and was also associated with unprotected sex (b = 0.20, SE = 0.06, t = 3.27, P < 0.01) while controlling for alcohol use (b = 0.28, SE = 0.07, t = 4.25, P < 0.001). The test for the mediated effect established that alcohol use was a significant mediator, accounting for 27% of the total effect of traumatic stress on unprotected sex. These results highlight the need to address traumatic stress among female venue patrons as an important precursor of HIV risk due to alcohol use.

Traumatic stress and the mediating role of alcohol use on HIV-related sexual risk behavior: Results from a longitudinal cohort of South African women who attend alcohol-serving venues

PubMed Central

Abler, Laurie; Sikkema, Kathleen J.; Watt, Melissa H.; Pitpitan, Eileen V.; Kalichman, Seth C.; Skinner, Donald; Pieterse, Desiree

2014-01-01

Background In South Africa, alcohol contributes to the HIV epidemic, in part, by influencing sexual behaviors. For some, high levels of alcohol consumption may be driven by previous traumatic experiences that result in traumatic stress. The purpose of this study was to quantify the longitudinal association between traumatic stress and unprotected sex among women who attend drinking venues and to assess whether this association was explained by mediation through alcohol use. Methods Data were collected in four waves over a year from a prospective cohort of 560 women who regularly attended alcohol-serving venues in a Cape Town township. Longitudinal mixed models examined: 1) the relationship between traumatic stress and counts of unprotected sex, and 2) whether alcohol use mediated the association between traumatic stress and unprotected sex. Results Most women reported elevated traumatic stress (80%) and hazardous alcohol use (88%) at least once during the study period. In models adjusted for covariates, traumatic stress was associated with unprotected sex (b=0.28, SE=0.06, t=4.82, p<.001). In addition, traumatic stress was associated with alcohol use (b=0.27, SE=0.02, t=14.25, p<.001), and was also associated with unprotected sex (b=0.20, SE=0.06, t=3.27, p<.01) while controlling for alcohol use (b=0.28, SE=0.07, t=4.25, p<.001). The test for the mediated effect established that alcohol use was a significant mediator, accounting for 27% of the total effect of traumatic stress on unprotected sex. Conclusions These results highlight the need to address traumatic stress among female venue patrons as an important precursor of HIV risk due to alcohol use. PMID:25394191

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

PubMed

Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

Spirituality in Recovery: A Lagged Mediational Analysis of Alcoholics Anonymous’ Principal Theoretical Mechanism of Behavior Change

PubMed Central

Kelly, John F.; Stout, Robert L.; Magill, Molly; Tonigan, J. Scott; Pagano, Maria E.

2010-01-01

Background Evidence indicates Alcoholics Anonymous (AA) can play a valuable role in recovery from alcohol use disorder. While AA itself purports it aids recovery through “spiritual” practices and beliefs, this claim remains contentious and has been only rarely formally investigated. Using a lagged, mediational analysis, with a large clinical sample of adults with alcohol use disorder, this study examined the relationships among AA, spirituality/religiousness, and alcohol use, and tested whether the observed relation between AA and better alcohol outcomes can be explained by spiritual changes. Method Adults (N = 1,726) participating in a randomized controlled trial of psychosocial treatments for alcohol use disorder (Project MATCH) were assessed at treatment intake, and 3, 6, 9, 12, and 15 months on their AA attendance, spiritual/religious practices, and alcohol use outcomes using validated measures. General linear modeling (GLM) and controlled lagged mediational analyses were utilized to test for mediational effects. Results Controlling for a variety of confounding variables, attending AA was associated with increases in spiritual practices, especially for those initially low on this measure at treatment intake. Results revealed AA was also consistently associated with better subsequent alcohol outcomes, which was partially mediated by increases in spirituality. This mediational effect was demonstrated across both outpatient and aftercare samples and both alcohol outcomes (proportion of abstinent days; drinks per drinking day). Conclusions Findings suggest that AA leads to better alcohol use outcomes, in part, by enhancing individuals’ spiritual practices and provides support for AA’s own emphasis on increasing spiritual practices to facilitate recovery from alcohol use disorder. PMID:21158876

The relationship of sex-related alcohol expectancies to alcohol consumption and sexual behavior.

PubMed

Leigh, B C

1990-07-01

Recent psychosocial research on alcohol expectancies--beliefs about the effects of alcohol on behavior, moods and emotions--has suggested that these expectancies mediate not only decisions about drinking but the alcohol effects displayed by those who have been drinking. Results of a study of drinking and sexual behavior showed that individuals of different gender and sexual orientation differed in their beliefs about the effects of alcohol on sexual responding. In addition, expectations of sexual enhancement and disinhibition were related to the initiation of sexual activity and to the proportion of sexual encounters that took place while drinking, and interacted with sex guilt to predict the amount drunk in the most recent sexual encounter. These results suggest that beliefs about the effects of alcohol on sex may affect the characteristics of sexual encounters that involve drinking.

Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells.

PubMed

Falkowski, Olga; An, Hee Jung; Ianus, I Andreea; Chiriboga, Luis; Yee, Herman; West, A Brian; Theise, Neil D

2003-09-01

In massive hepatic necrosis, hepatic stem cells constitute a canal of Hering derived, cytokeratin 19 (CK19) positive 'ductular reaction' (DR). Whether DRs in cirrhosis are activated stem cells (so called 'buds') or biliary metaplasia of cholestatic, injured hepatocytes is still debated. We investigate derivation of intraseptal hepatocytes (ISHs) from DRs and from the biliary tree in cirrhosis. Explants of hepatitis B and C, alcohol, primary biliary cirrhosis and primary sclerosing cholangitis-related cirrhosis were examined. ISHs were quantified and their associations with DRs and cholestasis recorded. 3D-reconstruction of ISHs and nearby bile ducts was performed in blocks from hepatitis C and primary sclerosing cholangitis cirrhosis. Seven hundred seventy five/830 (94%) ISHs were associated with CK19 positive DRs. ISHs without ductular reactions were more likely to show cholestatic features (P<0.0001). In 3D, ISHs were seen to bud directly from the biliary tree. In summary: ISHs: (1) are usually associated with stem cell-like DRs; (2) are rarely cholestatic, leaving the associated DRs unexplained; and (3) are linked to the biliary tree in 3D. Dynamic proliferation rates in hepatitis C over time suggest that hepatocyte replication diminishes in late stages, with an associated activation of the biliary stem cell compartment. We therefore suggest that the biliary tree, from at least its smaller branches up to the canals of Hering, are composed of or at least harbor facultative hepatic stem cells, and that ISH largely represent 'buds' of newly formed hepatocytes.

Early age alcohol use and later alcohol problems in adolescents: individual and peer mediators in a bi-national study.

PubMed

Mason, W Alex; Toumbourou, John W; Herrenkohl, Todd I; Hemphill, Sheryl A; Catalano, Richard F; Patton, George C

2011-12-01

This paper examines whether there is cross-national similarity in the longitudinal relationship between early age alcohol use and adolescent alcohol problems. Potential mechanisms underlying this relationship also are examined, testing adolescent alcohol use, low self-regulation, and peer deviance as possible mediators. Students (N = 1,945) participating in the International Youth Development Study, a longitudinal panel survey study, responded to questions on alcohol use and influencing factors, and were followed annually over a 3-year period from 2002 to 2004 (98% retention rate). State-representative, community student samples were recruited in grade 7 in Washington State, United States (US, n = 961, 78% of those eligible; Mage = 13.09, SD = .44) and Victoria, Australia (n = 984, 76% of those eligible; Mage = 12.93, SD = .41). Analyses were conducted using multiple-group structural equation modeling. In both states, early age alcohol use (age 13) had a small but statistically significant association with subsequent alcohol problems (age 15). Overall, there was little evidence for mediation of early alcohol effects. Low self-regulation prospectively predicted peer deviance, alcohol use, and alcohol problems in both states. Peer deviance was more positively related to alcohol use and low self-regulation among students in Victoria compared to students in Washington State. The small but persistent association of early age alcohol use with alcohol problems across both samples is consistent with efforts to delay alcohol initiation to help prevent problematic alcohol use. Self-regulation was an important influence, supporting the need to further investigate the developmental contribution of neurobehavioral disinhibition.

The risk of fractures among patients with cirrhosis or chronic pancreatitis.

PubMed

Bang, Ulrich Christian; Benfield, Thomas; Bendtsen, Flemming; Hyldstrup, Lars; Beck Jensen, Jens-Erik

2014-02-01

Cirrhosis and chronic pancreatitis (CP) are accompanied by inflammation and malnutrition. Both conditions can have negative effects on bone metabolism and promote fractures. We evaluated the risk of fractures among patients with CP or cirrhosis and determined the effect of fat malabsorption on fracture risk among patients with CP. We performed a retrospective cohort study using the Danish National Patient Register to identify patients diagnosed with CP or cirrhosis. We analyzed data collected from January 1, 1995, to December 31, 2010, on 20,769 patients (35.5% women with cirrhosis and 11,972 patients (33.5% women) with CP. Each patient was compared with 10 age- and sex-matched controls. We also assessed the risk of fractures among patients with CP who received pancreatic enzyme substitution (PES) for fat malabsorption. During the study period, bone fractures occurred in 3954 patients with cirrhosis and 2594 patients with CP. The adjusted hazard ratio (HR) for any fracture was 2.4 in patients with cirrhosis (95% confidence interval [CI], 2.2-2.5) and 1.7 in patients with CP (95% CI, 1.6-1.8). The relative risk of low-trauma fractures was highest among individuals younger than 50 years old. Alcohol as an etiology was associated with an increased risk of fracture compared with patients with nonalcoholic cirrhosis (HR, 2.4 vs 1.5; P < .0001) and CP (HR, 2.0 vs 1.5; P < .0001). Patients with CP receiving PES for fat malabsorption had a lower risk of fractures than other CP patients (HR, 0.8; 95% CI, 0.7-0.9). However, increasing the duration of treatment with PES was associated with an increased risk of fracture. Patients, especially younger patients, with cirrhosis or CP have an increased risk of fractures of all types. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Physiologic and laboratory correlates of depression, anxiety, and poor sleep in liver cirrhosis.

PubMed

Ko, Fang-Yuan; Yang, Albert C; Tsai, Shih-Jen; Zhou, Yang; Xu, Lie-Ming

2013-01-22

Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability (HRV) analyses, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. A total of 125 patients with cirrhosis and 55 healthy subjects were recruited. Each subject was assessed through routine biochemistry, 5-minutes ECG monitoring, and psychological ratings of depression, anxiety, and sleep. HRV analysis were used to evaluate autonomic functions. The relationship between depression, sleep, and physiologic correlates was assessed using a multiple regression analysis and stepwise method, controlling for age, duration of illness, and severity of cirrhosis. Reduced vagal-related HRV was found in patients with severe liver cirrhosis. Severity of cirrhosis measured by the Child-Pugh score was not correlated with depression or anxiety, and only had a weak correlation with poor sleep. The psychological distress in cirrhosis such as depression, anxiety, and insomnia were correlated specifically to increased levels of aspartate aminotransferase (AST), increased ratios of low frequency to high frequency power, or reduced nonlinear properties of HRV (α1 exponent of detrended fluctuation analysis). Increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression.

Psychoactive Medications Increase the Risk of Falls and Fall-related Injuries in Hospitalized Patients With Cirrhosis.

PubMed

Tapper, Elliot B; Risech-Neyman, Yesenia; Sengupta, Neil

2015-09-01

Reducing or eliminating falls is a focus of patient safety programs as well as health policy. Falls are tied to hospital reimbursement. However, little is known about the risk of falls among hospitalized patients with cirrhosis or factors that affect risk of falling. We conducted a retrospective cohort study of inpatients with cirrhosis from 2010 to 2013 at a liver transplant center. Our primary aim was to determine the clinical factors associated with falls and fall-related injuries for patients with cirrhosis. Our secondary aim was to describe the rate ratio of falls and fall-related injuries among patients with cirrhosis compared with general medical inpatients. During the study period, there were 1749 admissions to the liver service; 55 (3.1%) resulted in falls. Patients who fell were more likely to have received benzodiazepines (50.9% vs 16.7%, P < .0001) and antipsychotic agents (30.9% vs 7.3%, P < .0001). After adjusting for hepatic encephalopathy, the respective odds of a fall after benzodiazepine or antipsychotic exposure were 6.59 (95% confidence interval [CI], 3.76-11.59) and 3.72 (95% CI, 1.90-7.06). The adjusted risk of a fall-related injury was also significantly associated with benzodiazepine and antipsychotic agents, with respective odds ratios of 3.45 (95% CI, 1.39-8.23) and 3.42 (95% CI, 1.09-8.99). Fall-related injuries occurred at a rate of 1.70/1000 patient-days for patients with cirrhosis vs 0.5/1000 patient-days for patients in the general medical service. Accordingly, the rate ratio for a fall-related injury among patients with cirrhosis was 3.37 (95% CI, 1.99-5.72; P < .0001). Psychoactive medications are associated with an increased adjusted risk of falls and fall-related injuries in hospitalized patients with cirrhosis. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

The green eyed monster in the bottle: Relationship contingent self-esteem, romantic jealousy, and alcohol-related problems.

PubMed

DiBello, Angelo M; Rodriguez, Lindsey M; Hadden, Benjamin W; Neighbors, Clayton

2015-10-01

Previous research suggests that both jealousy and relationship contingent self-esteem (RCSE) are related to alcohol use and alcohol-related problems. No work, however, has examined these two constructs together as they relate to motives for alcohol use and alcohol-related problems. The current study aims to build upon emerging literature examining different types of jealousy (i.e., emotional, cognitive, and behavioral), relationship quality (i.e., satisfaction, commitment, closeness), RCSE, and alcohol use. More specifically, the current study aimed to examine the associations between RCSE and drinking to cope and RCSE and alcohol-related problems, in the context of the different types of jealousy. Moreover, the current study aimed to assess whether the associations between RCSE, jealousy, and drinking outcomes vary as a function of relationship quality. Two hundred and seventy seven individuals (87% female) at a large southern university participated in the study. They completed measures of RCSE, relationship satisfaction, commitment, closeness, and jealousy as well as alcohol-related outcomes. Using PROCESS, moderated mediational analyses were used to evaluate different types of jealousy as mediators of the association between RCSE and drinking to cope/alcohol-related problems. Further, we aimed to examine whether relationship quality moderated the association between RCSE and jealousy in predicting alcohol-related variables. Results indicated that cognitive jealousy mediated the association between both RCSE and drinking to cope and RCSE and alcohol-related problems. Further, relationship satisfaction, commitment, and closeness were all found to moderate the association between RSCE and cognitive jealousy such that at lower, but not higher levels of satisfaction, commitment, and closeness, cognitive jealousy mediated the association between RCSE and drinking to cope and RCSE and alcohol-related problems. Copyright © 2015. Published by Elsevier Ltd.

Workplace harassment/abuse and alcohol-related outcomes: the mediating role of psychological distress.

PubMed

Richman, Judith A; Shinsako, Stephanie A; Rospenda, Kathleen M; Flaherty, Joseph A; Freels, Sally

2002-07-01

This article embraces a tension-reduction or self-medication perspective on alcohol use and misuse. It empirically addresses the role that psychological distress plays in mediating the relationships between harassing and abusive interpersonal experiences in the workplace and altered alcohol use and misuse. A mail survey was completed by 2,038 university employees (1,098 women and 940 men) at two points in time. Specific hypotheses were tested involving (1) the extent to which the onset and chronicity of harassment and abuse predicted varied Wave-2 drinking outcomes, (2) the extent to which the onset and chronicity of harassment and abuse predicted three forms of Wave-2 psychological distress, (3) the associations between Wave-2 psychological distress and drinking outcomes and (4) the extent to which the associations between harassment/abuse and drinking outcomes disappeared when the salient forms of symptomatic distress functioned as control variables. The data showed that harassment and abuse predicted drinking outcomes and psychological distress, and that the associations between harassment/abuse and drinking outcomes were partially mediated by distress. The findings lend support to the tension-reduction perspective and have important implications for intervention and prevention involving workplace harassment and abuse.

Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

PubMed

Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

2015-10-01

Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

[Liver cirrhosis patogenetics: polymorphism of glutation S-transferase genes].

PubMed

Goncharova, I A; Rachkovskiĭ, M I; Beloborodova, E V; Gamal' Abd El'-Aziz Nasar, Kh; Puzyrev, V P

2010-01-01

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

Recent Advancements in Diagnosis and Therapy of Liver Cirrhosis.

PubMed

Romanelli, Roberto Giulio; Stasi, Cristina

2016-01-01

Cirrhosis is a diffuse pathophysiological state of the liver considered to be the final stage of various liver injuries, characterized by chronic necroinflammatory and fibrogenetic processes, with subsequent conversion of normal liver architecture into structurally abnormal nodules, dense fibrotic septa, concomitant parenchymal exaustment and collapse of the liver tissue. Alcoholic liver disease and chronic infections due to HBV and/or HCV constitute the main causes of liver cirrhosis worldwide. During a lag time of 15 to 30 years, chronic liver diseases can lead to liver cirrhosis and its complications. Active hepatic inflammation plays a pivotal role in the inflammation- necrosis-regeneration process, which eventually leads to liver cirrhosis and hepatocellular carcinoma. Prognosis of liver cirrhosis is highly variable and influenced by several variables, such as etiology, severity of liver disease, presence of complications and comorbidities. In advanced cirrhosis, survival decreases to one or two years. Correct advanced diagnosis and selected treatment with different molecules may help in understanding mechanisms of fibrogenesis, the driving forces of cirrhosis's pathogenesis, and the scrupulous approach to more effective therapeutic procedures. Prevention of fibrosis with further deterioration of liver function through specific treatments is always required, through the removal of the underlying causes of liver disease. Advanced liver disease, with subsequent complications, requires targeted treatment. Therefore, the aim of this review is to assess the diagnosis and treatment of liver cirrhosis on the pathophysiological bases, searching for relevant studies published in English using the PubMed database from 2011 to the present.

Do excise taxes save lives? The Irish experience with alcohol taxation.

PubMed

Walsh, B M

1987-12-01

This paper studies the effects of changes in the level of indirect taxation of alcoholic beverages on alcohol-related problems. Using time series data for Ireland the following topics are explored: (1) the effect of changes in taxation on the retail price of alcohol; (2) the effect of changes in the retail price on the consumption of alcohol; and (3) the association between changes in alcohol consumption and the incidence of certain alcohol-related problems, such as deaths from liver cirrhosis and fatal road accidents. The evidence is that a relatively small number of alcohol-related deaths would be averted by higher alcohol taxes. The effect of heavier taxation on the distribution of purchasing power is discussed.

Social networks as mediators of the effect of Alcoholics Anonymous.

PubMed

Kaskutas, Lee Ann; Bond, Jason; Humphreys, Keith

2002-07-01

This study tested the hypothesis that the relationship between Alcoholics Anonymous (AA) involvement and reduced substance use is partially explained (or 'mediated') by changes in social networks. This is a naturalistic longitudinal study of the course of alcohol problems. Study sites were the 10 largest public and private alcohol treatment programs in a northern California county. Three hundred and seventy-seven men and 277 women were recruited upon seeking treatment at study sites. At baseline and 1-year follow-up, we assessed alcohol consequences and dependence symptoms, consumption, social support for abstinence, pro-drinking social influences and AA involvement. In the structural equation model, AA involvement was a significant predictor of lower alcohol consumption and fewer related problems. The size of this effect decreased by 36% when network size and support for drinking were included as mediators. In logistic regression models predicting abstinence at follow-up, AA remained highly significant after including social network variables but was again reduced in magnitude. Thirty-day abstinence was predicted by AA involvement (OR=2.9), not having pro-drinking influences in one's network (OR=0.7) and having support for reducing consumption from people met in AA (versus no support; OR=3.4). In contrast, having support from non-AA members was not a significant predictor of abstinence. For alcohol-related outcomes other than abstinence, significant relationships were found for both AA-based and non-AA-based support. The type of social support specifically given by AA members, such as 24-hour availability, role modeling and experientially based advice for staying sober, may help to explain AA's mechanism of action. Results highlight the value of focusing on outcomes reflective of AA's goals (such as abstinence) when studying how AA works.

Study of liver cirrhosis over ten consecutive years in Southern China

PubMed Central

Wang, Xing; Lin, Shang-Xiong; Tao, Jin; Wei, Xiu-Qing; Liu, Yuan-Ting; Chen, Yu-Ming; Wu, Bin

2014-01-01

2001-2005 with that in 2006-2010, the proportion of viral hepatitis decreased from 84.7% to 78.3% (P < 0.001), and the proportion of HBV-induced LC also decreased from 81.9% to 74.6% (P < 0.001). The incidence of mixed etiology, cryptogenic cirrhosis, and autoimmune diseases increased by 3.1% (P < 0.001), 0.5% (P = 0.158), and 1.3% (P < 0.001), respectively. Alcohol-induced LC remained relatively steady over the 10-year period. The ORs of the development of UGIB between HBV and other major etiologies were as follows: HCV, 1.07; alcohol, 1.89; autoimmune, 0.90; mixed etiology, 0.83; and cryptogenic, 1.76. The ORs of the occurrence of HCC between HBV and other major etiologies were as follows: HCV, 0.54; alcohol, 0.16; autoimmune, 0.05; mixed etiology, 0.58; and cryptogenic, 0.60. CONCLUSION: The major etiology of liver cirrhosis in Southern China is viral hepatitis. However, the proportions of viral hepatitis and HBV are gradually decreasing. Alcoholic LC patients exhibit a greater risk of experiencing UGIB, and HBV LC patients may have a greater risk of HCC. PMID:25309085

Gastrointestinal dysfunction in liver cirrhosis

PubMed Central

Kalaitzakis, Evangelos

2014-01-01

Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis. PMID:25356031

Pathophysiology and Management of Alcoholic Liver Disease: Update 2016.

PubMed

Stickel, Felix; Datz, Christian; Hampe, Jochen; Bataller, Ramon

2017-03-15

Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.

Physiologic and laboratory correlates of depression, anxiety, and poor sleep in liver cirrhosis

PubMed Central

2013-01-01

Background Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability (HRV) analyses, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. Methods A total of 125 patients with cirrhosis and 55 healthy subjects were recruited. Each subject was assessed through routine biochemistry, 5-minutes ECG monitoring, and psychological ratings of depression, anxiety, and sleep. HRV analysis were used to evaluate autonomic functions. The relationship between depression, sleep, and physiologic correlates was assessed using a multiple regression analysis and stepwise method, controlling for age, duration of illness, and severity of cirrhosis. Results Reduced vagal-related HRV was found in patients with severe liver cirrhosis. Severity of cirrhosis measured by the Child-Pugh score was not correlated with depression or anxiety, and only had a weak correlation with poor sleep. The psychological distress in cirrhosis such as depression, anxiety, and insomnia were correlated specifically to increased levels of aspartate aminotransferase (AST), increased ratios of low frequency to high frequency power, or reduced nonlinear properties of HRV (α1 exponent of detrended fluctuation analysis). Conclusions Increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression. PMID:23339829

Cortical NMDA receptor expression in human chronic alcoholism: influence of the TaqIA allele of ANKK1.

PubMed

Ridge, Justin P; Dodd, Peter R

2009-10-01

Real-time RT-PCR normalized to GAPDH was used to assay N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunit mRNA in human autopsy cortex tissue from chronic alcoholics with and without comorbid cirrhosis of the liver and matched controls. Subunit expression was influenced by the subject's genotype. The TaqIA polymorphism selectively modulated NMDA receptor mean transcript expression in cirrhotic-alcoholic superior frontal cortex, in diametrically opposite ways in male and female subjects. Genetic make-up may differentially influence vulnerability to brain damage by altering the excitation: inhibition balance, particularly in alcoholics with comorbid cirrhosis of the liver. The TaqIA polymorphism occurs within the poorly characterised ankyrin-repeat containing kinase 1 (ANKK1) gene. Using PCR, ANKK1 mRNA transcript was detected in inferior temporal, occipital, superior frontal and primary motor cortex of control human brain. ANKK1 expression may mediate the influence of the TaqIA polymorphism on phenotype.

Metastatic lung adenocarcinoma related α-Fetoprotein elevation in a patient with HBV-related cirrhosis.

PubMed

Hamamci, Mevlut; Karaahmet, Fatih; Akinci, Hakan; Kilincalp, Serta; Acıkgoz, Ruchan; Coban, Sahin; Yuksel, Ilhami

2015-12-01

HCC is the most common type of primary liver tumor. The Practice Guideline, AASLD, for HCC recommended surveillance of HBV carriers at high risk of HCC with US every 6-12 months. Laboratory surveillance option is the measurement of serum α-fetoprotein level which has long been used for the diagnosis of HCC. But, increased serum levels of α-fetoprotein are also seen in acute hepatitis, cirrhosis, and malignancies include yolk sac carcinoma, neuroblastoma, hepatoblastoma, gastric and lung carcinoma. Because of elevation α-fetoprotein in these malignancies, liver mass with an elevated α-fetoprotein does not directly indicate HCC. For these reason, clinicians evaluating patient with liver mass and HBV-related cirrhosis should be vigilant for other case of α-fetoprotein elevation. © Acta Gastro-Enterologica Belgica.

Liver membrane antibodies in alcoholic liver disease: 1. prevalence and immunoglobulin class.

PubMed Central

Burt, A D; Anthony, R S; Hislop, W S; Bouchier, I A; MacSween, R N

1982-01-01

Using an indirect immunofluorescence technique liver membrane antibodies of IgG and IgA class have been demonstrated in a statistically significant proportion of sera from patients with alcoholic hepatitis and alcoholic cirrhosis. IgG and IgA class antibodies were found respectively in 23 and 25% of 48 patients with alcoholic hepatitis, in 27 and 33% of 84 with active cirrhosis, and 67 and 58% of 12 with inactive cirrhosis. These results provide evidence of a humoral immune response in alcoholic liver disease which is directed against, as yet undefined, liver-cell membrane antigens. Images Fig. 1 PMID:7040177

Common polymorphisms in interleukin genes (IL4, IL6, IL8 and IL12) are not associated with alcoholic liver disease or alcoholism in Spanish men.

PubMed

Marcos, Miguel; Pastor, Isabel; González-Sarmiento, Rogelio; Laso, Francisco-Javier

2009-03-01

Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: -33T>C IL4, -174 G>C IL6, -251 T>A IL8 and 1188 A>C IL12B. 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation-maximization algorithm and haplotype frequencies were compared. We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either. Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.

Unplanned Drinking and Alcohol-Related Problems: A Preliminary Test of the Model of Unplanned Drinking Behavior

PubMed Central

Pearson, Matthew R.; Henson, James M.

2013-01-01

Much research links impulsivity with alcohol use and problems. In two studies, unplanned (or impulsive) drinking is assessed directly to determine whether it has direct effects on alcohol use and alcohol-related problems. In study 1, we examined whether unplanned drinking serves as a proximal mediator of the effects of impulsivity-like traits on alcohol-related outcomes. With a sample of 211 college student drinkers, we found that the Unplanned Drinking Scale was significantly related to alcohol use, and perhaps more importantly, had a direct effect on alcohol-related problems even after controlling for frequency and quantity of alcohol use. Further, unplanned drinking partially mediated the effects of negative urgency on alcohol-related problems. In study 2, we examined whether unplanned drinking accounts for unique variance in alcohol-related outcomes when controlling for use of protective behavioral strategies. With a sample of 170 college students, we replicated the findings of Study 1 in that the Unplanned Drinking Scale had a significant direct effect on alcohol-related problems even after controlling for alcohol use; further, this effect was maintained when controlling for use of protective behavioral strategies. Limitations include the modest sample sizes and the cross-sectional design. Future directions for testing the Model of Unplanned Drinking Behavior are proposed. PMID:23276312

Cirrhosis and Advanced Fibrosis in Hispanics in Texas: The Dominant Contribution of Central Obesity

PubMed Central

Jiao, Jingjing; Watt, Gordon P.; Lee, MinJae; Rahbar, Mohammad H.; Vatcheva, Kristina P.; Pan, Jen-Jung; McCormick, Joseph B.; Fisher-Hoch, Susan P.; Fallon, Michael B.; Beretta, Laura

2016-01-01

Liver cirrhosis is a leading cause of death in Hispanics and Hispanics who live in South Texas have the highest incidence of liver cancer in the United States. We aimed at determining the prevalence and associated risk factors of cirrhosis in this population. Clinical and demographic variables were extracted for 2466 participants in the community-based Cameron County Hispanic Cohort in South Texas. Aspartate transaminase to Platelet Ratio Index (APRI) was used to predict cirrhosis in Cameron County Hispanic Cohort. The prevalence of cirrhosis using APRI≥2 was 0.94%, which is nearly 4-fold higher than the national prevalence. Using APRI≥1, the overall prevalence of cirrhosis/advanced fibrosis was 3.54%. In both analyses, highest prevalence was observed in males, specifically in the 25–34 age group. Risk factors independently associated with APRI≥2 and APRI≥1 included hepatitis C, diabetes and central obesity with a remarkable population attributable fraction of 52.5% and 65.3% from central obesity, respectively. Excess alcohol consumption was also independently associated with APRI≥2. The presence of patatin-like phospholipase domain-containing-3 gene variants was independently associated with APRI≥1 in participants >50 years old. Males with both central obesity and excess alcohol consumption presented with cirrhosis/advanced fibrosis at a young age. Alarmingly high prevalence of cirrhosis and advanced fibrosis was identified in Hispanics in South Texas, affecting young males in particular. Central obesity was identified as the major risk factor. Public health efforts are urgently needed to increase awareness and diagnosis of advanced liver fibrosis in Hispanics. PMID:26950933

Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB–mediated mechanism

PubMed Central

Qiu, Jia; Thapaliya, Samjhana; Runkana, Ashok; Yang, Yu; Tsien, Cynthia; Mohan, Maradumane L.; Narayanan, Arvind; Eghtesad, Bijan; Mozdziak, Paul E.; McDonald, Christine; Stark, George R.; Welle, Stephen; Naga Prasad, Sathyamangla V.; Dasarathy, Srinivasan

2013-01-01

Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-κB–dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IκB kinase, NF-κB nuclear translocation, binding of the NF-κB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-κB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients. PMID:24145431

Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism.

PubMed

Qiu, Jia; Thapaliya, Samjhana; Runkana, Ashok; Yang, Yu; Tsien, Cynthia; Mohan, Maradumane L; Narayanan, Arvind; Eghtesad, Bijan; Mozdziak, Paul E; McDonald, Christine; Stark, George R; Welle, Stephen; Naga Prasad, Sathyamangla V; Dasarathy, Srinivasan

2013-11-05

Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-κB-dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IκB kinase, NF-κB nuclear translocation, binding of the NF-κB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-κB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients.

PTSD Symptoms, Emotion Dysregulation, and Alcohol-Related Consequences Among College Students With a Trauma History.

PubMed

Tripp, Jessica C; McDevitt-Murphy, Meghan E; Avery, Megan L; Bracken, Katherine L

2015-01-01

Posttraumatic stress disorder (PTSD), alcohol use, and alcohol-related consequences have been linked to emotion dysregulation. Sex differences exist in both emotion regulation dimensions and alcohol use patterns. This investigation examined facets of emotion dysregulation as potential mediators of the relationship between PTSD symptoms and alcohol-related consequences and whether differences may exist across sexes. Participants were 240 college students with a trauma history who reported using alcohol within the past three months and completed measures of PTSD symptoms, emotion dysregulation, alcohol consumption, alcohol-related consequences, and negative affect. The six facets of emotion dysregulation were examined as mediators of the relationship between PTSD symptoms and alcohol-related consequences in the full sample and by sex. There were differences in sexes on several variables, with women reporting higher PTSD scores and lack of emotional awareness. Men reported significantly more drinks per week in a typical week and a heavy week. There were significant associations between the variables for the full sample, with PTSD showing associations with five facets of emotion dysregulation subscales: impulse control difficulties when upset, difficulties engaging in goal-directed behavior, nonacceptance of emotional responses, lack of emotional clarity, and limited access to emotion regulation strategies. Alcohol-related consequences were associated with four aspects of emotion dysregulation: impulse control difficulties when upset, difficulties engaging in goal-directed behavior, nonacceptance of emotional responses, and limited access to emotion regulation strategies. Two aspects of emotion regulation, impulse control difficulties and difficulties engaging in goal directed behavior, mediated the relationship between PTSD symptoms and alcohol-related consequences in the full sample, even after adjusting for the effects of negative affect. When examined separately by

[Behaviour of the LAP (leucine-amino-peptidase) in the serum of blood in subjects affected of cirrhosis of the liver in stage ascitical (author's transl)].

PubMed

Pace, M; Fernandes, D

1980-12-01

The AA. have studied behaviour of the LAP (leucine-amino-peptidase) in the serum of blood in subjects affected of cirrhosis of the liver in stage ascitical, of cause toxic-alcoholic excluding about of the casuistry the cirrhosis of the another cause and the cirrhosis that are compled white an obstruction in and extrahepatic standard biliary cirrhosis 1 degree e 2 degree. After the exposition of the casuistry in the registred normality of the test (seric-LAP) in some cases of hepatic-alcoholic cirrhosis, the AA. concluded considering the LAP an indicator only of the obstruction in and extra-hepatic, consistent with hepatic-organ well operating; do not be a secure test to follow development of a chronic hepatitis of any kind, even if in the hepatic disease is present an infiltration and an overturning of the hepatic-lobule, like it is normally in the hepatic alcoholic diseases.

Cirrhosis is Under-recognized in Patients Subsequently Diagnosed with Hepatocellular Cancer

PubMed Central

Walker, Megan; El-Serag, Hashem B.; Sada, Yvonne; Mittal, Sahil; Ying, Jun; Duan, Zhigang; Richardson, Peter; Davila, Jessica A.; Kanwal, Fasiha

2015-01-01

Background Most clinical practice guidelines recommend screening for HCC in patients with cirrhosis. However, patients with compensated cirrhosis are often asymptomatic and may remain unrecognized for years. Aims To determine the extent to which cirrhosis is unrecognized in a US Veteran population with HCC and to evaluate the association between lack of cirrhosis recognition and stage of HCC at diagnosis. Methods We reviewed the electronic medical records of a random sample of HCC cases diagnosed in the national Veterans Affairs system between 2005 and 2011. We conducted multivariable analyses adjusting for patients’ demographics, comorbidity, etiology of underlying disease, and healthcare utilization including HCC surveillance. Results Of 1201 patients with HCC and cirrhosis, 24.6% had unrecognized cirrhosis prior to HCC diagnosis. Older patients (>65yr, odds ratio [OR] 2.32), African Americans (OR 1.93), patients with alcoholic or NAFLD liver disease (OR 1.69 and 4.77 respectively), HIV (OR 3.02), and fewer comorbidities (Deyo 0 vs. 3, OR 2.42) had significantly higher odds of having unrecognized cirrhosis than comparison groups. Furthermore, patients with unrecognized cirrhosis were 6.5 times more likely to have advanced stage HCC at diagnosis. The effect of cirrhosis recognition on HCC stage remained significant after adjusting for pre-specified covariates (OR 3.37). Conclusions In one fourth of patients, cirrhosis was unrecognized prior to HCC diagnosis, and this group was significantly more likely to have advanced stage HCC. These findings emphasize the importance of timely evaluation for cirrhosis in at-risk populations as a critical step to improving outcomes for HCC patients. PMID:26784271

Bidirectional Relations of Impulsive Personality and Alcohol Use Across Three Waves of Data Collection.

PubMed

Kaiser, Alison J; Davis, Heather A; Milich, Richard; Smith, Gregory T; Charnigo, Richard

2018-06-11

To explore the bidirectional relations between alcohol use and three impulsive personality traits, to advance understanding of risk processes. 525 college students (mean age = 18.95 years) recruited in August 2008 and 2009 and followed up annually for three years. Personality and past/current substance use were assessed. T2 sensation seeking mediated the predictive relationship between T1 and T3 alcohol use, and T2 alcohol use mediated the predictive relationship between T1 and T3 sensation seeking. In addition, T2 alcohol problems mediated the predictive relationship between T1 alcohol use and T3 negative urgency. Findings support a bidirectional relationship between sensation seeking and alcohol use, and drinking anticipates drinking problems, which predict increases in negative urgency. For some individuals, there appears to be an ongoing process of increased risk in the form of increases in both drinking and high-risk personality traits.

[Current status and perspectives of diagnosis and treatment of complications related to liver cirrhosis].

PubMed

Nan, Y M

2017-04-20

Liver cirrhosis is the severe period of chronic liver diseases, especially decompensated liver cirrhosis and its complications, such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury, and hepatocellular carcinoma, which greatly affect patients' quality of life and even threaten their lives. Early prevention and treatment of the causes of development and progression and pathogenic mechanism may slow down or reverse liver cirrhosis and its severe complications. Once the disease progresses to portal hypertension and related complications, it is very important to select preventive measures for acute exacerbation of different complications, as well as the methods and timing for treatment in acute stage, which may help to save patients' lives and improve their prognosis.

Linking masculinity to negative drinking consequences: the mediating roles of heavy episodic drinking and alcohol expectancies.

PubMed

Wells, Samantha; Flynn, Andrea; Tremblay, Paul F; Dumas, Tara; Miller, Peter; Graham, Kathryn

2014-05-01

This study extends previous research on masculinity and negative drinking consequences among young men by considering mediating effects of heavy episodic drinking (HED) and alcohol expectancies. We hypothesized that masculinity would have a direct relationship with negative consequences from drinking as well as indirect relationships mediated by HED and alcohol expectancies of courage, risk, and aggression. A random sample of 1,436 college and university men ages 19-25 years completed an online survey, including conformity to masculine norms, alcohol-related expectancies, HED, and negative drinking consequences. Regression analyses and structural equation modeling were used. Six of seven dimensions of masculinity and the alcohol expectancy scales were significantly associated with both HED and negative consequences. In multivariate regression models predicting HED and negative consequences, the playboy and violence dimensions of masculinity and the risk/aggression alcohol expectancy remained significant. HED and the risk-taking dimension of masculinity were also significant in the model predicting negative consequences. The structural equation model indicated that masculinity was directly associated with HED and negative consequences but also influenced negative consequences indirectly through HED and alcohol expectancies. The findings suggest that, among young adult male college and university students, masculinity is an important factor related to both HED and drinking consequences, with the latter effect partly mediated by HED and alcohol expectancies. Addressing male norms about masculinity may help to reduce HED and negative consequences from drinking.

Insulin-Like Growth Factor-1 Deficiency and Cirrhosis Establishment

PubMed Central

de la Garza, Rocio G.; Morales-Garza, Luis Alonso; Martin-Estal, Irene; Castilla-Cortazar, Inma

2017-01-01

Cirrhosis represents the final stage of chronic liver damage, which can be due to different factors such as alcohol, metabolic syndrome with liver steatosis, autoimmune diseases, drugs, toxins, and viral infection, among others. Nowadays, cirrhosis is an important health problem and it is an increasing cause of morbidity and mortality, being the 14th most common cause of death worldwide. The physiopathological pathways that lead to fibrosis and finally cirrhosis partly depend on the etiology. Nevertheless, some common features are shared in this complex mechanism. Recently, it has been demonstrated that cirrhosis is a dynamic process that can be altered in order to delay or revert fibrosis. In addition, when cirrhosis has been established, insulin-like growth factor-1 (IGF-1) deficiency or reduced availability is a common condition, independently of the etiology of chronic liver damage that leads to cirrhosis. IGF-1 deprivation seriously contributes to the progressive malnutrition of cirrhotic patient, increasing the vulnerability of the liver to establish an inflammatory and oxidative microenvironment with mitochondrial dysfunction. In this context, IGF-1 deficiency in cirrhotic patients can justify some of the common characteristics of these individuals. Several studies in animals and humans have been done in order to test the replacement of IGF-1 as a possible therapeutic option, with promising results. PMID:28270882

Different pathways explain alcohol related problems in female and male college students

PubMed Central

Pedrelli, P.; Collado, A.; Shapero, B. G.; Brill, C.; MacPherson, L.

2016-01-01

Objectives Comprehensive models elucidating the intricate associations of depressive symptoms, coping motives, alcohol use, alcohol-related problems (ARP) and gender among young adults have been scarcely examined. This study investigated relationships among these variables and the effect of gender on these pathways. Methods College students (N = 163; 49.7% female) completed self-report measures on alcohol consumption, depressive symptoms, coping motives, and ARPs. Results Structural equation modeling showed that the association between depressive symptoms and ARPs was mediated by coping motives in both females and males. However, frequency of heavy alcohol use mediated the association between depressive symptoms and ARPs in females but not in males. Conclusions Different models explain the association between depressive symptoms and ARPs in male and female college students. Prevention programs aimed at reducing ARPs should focus on increasing alcohol screening among students with depressive symptoms, teaching coping skills, and emphasizing moderation in alcohol consumption. PMID:27219280

The relation of personality to alcohol abuse/dependence in a high-risk sample.

PubMed

Loukas, A; Krull, J L; Chassin, L; Carle, A C

2000-12-01

The current study had two goals. The first goal was to test the mediational role of young adult personality in the relation between parental alcoholism and young adult alcoholism. The second was to examine the associations between personality and alcohol use motives and reasons to limit drinking in order to explore possible mechanisms by which personality may influence alcohol abuse/dependence. Multilevel modeling techniques were used to analyze data obtained from a community sample of young adult children of alcoholics and demographically matched controls. Results revealed that young adult neuroticism and agreeableness each, in part, mediated the effect of parental alcoholism on young adult alcoholism. Moreover, individuals high in neuloticism reported stronger coping motives to use alcohol, individuals low in agreeableness reported stronger coping motives and weaker upbringing reasons to limit drinking, and individuals low in conscientiousness reported stronger coping and enhancement motives to use alcohol, and weaker performance reasons to limit drinking.

Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer.

PubMed

Wu, Dongyan; Yang, Haitao; Winham, Stacey J; Natanzon, Yanina; Koestler, Devin C; Luo, Tiane; Fridley, Brooke L; Goode, Ellen L; Zhang, Yanbo; Cui, Yuehua

2018-03-01

Epigenetic factors and consumption of alcohol, which suppresses DNA methylation, may influence the development and progression of epithelial ovarian cancer (EOC). However, there is a lack of understanding whether these factors interact to affect the EOC risk. In this study, we aimed to gain insight into this relationship by identifying leukocyte-derived DNA methylation markers acting as potential mediators of alcohol-associated EOC. We implemented a causal inference test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to examine CpG sites that mediate the association between alcohol consumption and EOC risk. We modified one step of the CIT by adopting a high-dimensional inference procedure. The data were based on 196 cases and 202 age-matched controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent potential mediators of the relationship between alcohol consumption and EOC case-control status. Implementation of the VanderWeele and Vansteelandt multiple mediator model further revealed that these two CpGs were the key mediators. Decreased methylation at both CpGs was more common in cases who drank alcohol at the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which has been previously shown to be overexpressed in EOC. These findings suggest two CpGs may serve as novel biomarkers for EOC susceptibility.

Regression of esophageal varices and splenomegaly in two patients with hepatitis-C-related liver cirrhosis after interferon and ribavirin combination therapy.

PubMed

Lee, Soon Jae; Cho, Yoo-Kyung; Na, Soo-Young; Choi, Eun Kwang; Boo, Sun Jin; Jeong, Seung Uk; Song, Hyung Joo; Kim, Heung Up; Kim, Bong Soo; Song, Byung-Cheol

2016-09-01

Some recent studies have found regression of liver cirrhosis after antiviral therapy in patients with hepatitis C virus (HCV)-related liver cirrhosis, but there have been no reports of complete regression of esophageal varices after interferon/peg-interferon and ribavirin combination therapy. We describe two cases of complete regression of esophageal varices and splenomegaly after interferon-alpha and ribavirin combination therapy in patients with HCV-related liver cirrhosis. Esophageal varices and splenomegaly regressed after 3 and 8 years of sustained virologic responses in cases 1 and 2, respectively. To our knowledge, this is the first study demonstrating that complications of liver cirrhosis, such as esophageal varices and splenomegaly, can regress after antiviral therapy in patients with HCV-related liver cirrhosis.

Insulin resistance in clinical and experimental alcoholic liver disease

PubMed Central

Carr, Rotonya M.; Correnti, Jason

2015-01-01

Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of health care dollars annually. Since the advent of the obesity epidemic, insulin resistance and diabetes have become common clinical findings in patients with ALD; and the development of insulin resistance predicts the progression from simple steatosis to cirrhosis in ALD patients. Both clinical and experimental data implicate the impairment of several mediators of insulin signaling in ALD, and experimental data suggest that insulin-sensitizing therapies improve liver histology. This review explores the contribution of impaired insulin signaling in ALD and summarizes the current understanding of the synergistic relationship between alcohol and nutrient excess in promoting hepatic inflammation and disease. PMID:25998863

Transjugular Intrahepatic Portosystemic Shunt for Treatment of Cirrhosis-related Chylothorax and Chylous Ascites: Single-institution Retrospective Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kikolski, Steven G., E-mail: skikolski@ucsd.edu; Aryafar, Hamed, E-mail: haryafar@ucsd.edu; Rose, Steven C., E-mail: scrose@ucsd.edu

2013-08-01

PurposeTo investigate the efficacy and safety of the use of transjugular intrahepatic portosystemic shunt (TIPS) creation to treat cirrhosis-related chylous collections (chylothorax and chylous ascites).MethodsWe retrospectively reviewed data from four patients treated for refractory cirrhosis-related chylous collections with TIPS at our institution over an 8 year period.ResultsOne patient had chylothorax, and three patients had concomitant chylothorax and chylous ascites. There were no major complications, and the only procedure-related complications occurred in two patients who had mild, treatable hepatic encephalopathy. All patients had improvement as defined by decreased need for thoracentesis or paracentesis, with postprocedure follow-up ranging from 19 to 491more » days.ConclusionTIPS is a safe procedure that is effective in the treatment of cirrhosis-related chylous collections.« less

Drinking to cope mediates the relationship between depression and alcohol risk: Different pathways for college and non-college young adults.

PubMed

Kenney, Shannon R; Anderson, Bradley J; Stein, Michael D

2018-05-01

It is well-established that drinking to cope with negative affective states mediates the relationship between depressed mood and alcohol risk outcomes among college students. Whether non-college emerging adults exhibit a similar pathway remains unknown. In the current study, we compared the mediating role of coping motives in the relationship between depressive symptoms and drinking risk outcomes (heavy episodic drinking and alcohol problems) in college and non-college emerging adult subgroups. Participants were three hundred forty-one community-recruited 18-25year olds reporting past month alcohol use. We used a structural equation modeling (SEM) for our primary mediation analysis and bias-corrected bootstrap resampling for testing the statistical significance of mediation. Participants averaged 20.8 (±1.97) years of age, 49% were female, 67.7% were White, 34.6% were college students, and 65.4% were non-college emerging adults. College and non-college emerging adults reported similar levels of drinking, alcohol problems, and drinking to cope with negative affect, and drinking to cope was associated with alcohol-related problems in both samples. However, while drinking to cope mediated the relationship between depressed mood and alcohol problems among students, it did not mediate the pathway among non-college emerging adults. These findings caution against extending college-based findings to non-college populations and underscore the need to better understand the role of coping motives and other intervening factors in pathways linking depressed mood and alcohol-related risk in non-college emerging adults. Copyright © 2018 Elsevier Ltd. All rights reserved.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

PubMed Central

Lee, Sangheun; Kim, Do Young

2014-01-01

Chronic hepatitis B (CHB) infection is a major public health problem associated with significant morbidity and mortality worldwide. Twenty-three percent of patients with CHB progress naturally to liver cirrhosis, which was earlier thought to be irreversible. However, it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs. Thus, early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB. Liver biopsy is the reference standard for assessment of liver fibrosis. However, the method is invasive, and is associated with pain and complications that can be fatal. In addition, intra- and inter-observer variability compromises the accuracy of liver biopsy data. Only small tissue samples are obtained and fibrosis is heterogeneous in such samples. This confounds the two types of observer variability mentioned above. Such limitations have encouraged development of non-invasive methods for assessment of fibrosis. These include measurements of serum biomarkers of fibrosis; and assessment of liver stiffness via transient elastography, acoustic radiation force impulse imaging, real-time elastography, or magnetic resonance elastography. Although significant advances have been made, most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection. In the present review, we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice. PMID:24574713

Prevalence of cirrhosis in patients with thrombocytopenia who receive bone marrow biopsy.

PubMed

Sheikh, Muhammad Y; Raoufi, Rahim; Atla, Pradeep R; Riaz, Muhammad; Oberer, Chad; Moffett, Michael J

2012-01-01

Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM) biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown. Between fiscal years 2006-2010, 744 patients (≥18 years) who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study. Of 203 patients, 136 (67%) had a normal and 67 (33%) had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9). 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001). Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH) (47%), followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI) (33.4 vs. 25.8, P < 0.001) and lower MELD scores (11.1 vs. 16, P = 0.028) when compared to non-NASH patients with cirrhosis. Approximately, one third (35%) of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia.

Patient-perceived barriers to lifestyle interventions in cirrhosis.

PubMed

Ney, Michael; Gramlich, Leah; Mathiesen, Vanessa; Bailey, Robert J; Haykowsky, Mark; Ma, Mang; Abraldes, Juan G; Tandon, Puneeta

2017-01-01

Sarcopenia, muscle weakness, and physical frailty are independent predictors of mortality in cirrhosis. These adverse prognostic factors are potentially modifiable with lifestyle interventions, including adequate nutritional intake and physical activity. Our aim was to identify patient-perceived barriers and enablers to these interventions. Adult patients with cirrhosis were prospectively recruited from two tertiary care liver clinics. Patients were excluded if they had hepatocellular carcinoma beyond transplant criteria, other active malignancy, or advanced chronic disease. A total of 127 patients (mean age: 60 ± 9 years, 58% males, and 48% with Child-Pugh-B/C (CP-B/C) disease) were included. Two-thirds of the patients had cirrhosis related to alcohol or hepatitis C. CP-B/C patients were more likely to take oral nutritional supplements (56% vs 29%) and less likely to consume animal protein daily (66% vs 85%) when compared to CP-A patients. Early satiety, altered taste, and difficulty in buying/preparing meals were more common in CP-B/C patients and even present in 20-30% of CP-A patients. Most patients reported adequate funds to purchase food. As quantified by the International Physical Activity Questionnaire-Short Form, 47% reported low activity levels, with no significant differences between groups. CP-B/C patients were more fatigued with exercise, however, overall Exercise Benefits/Barriers Scale scores were similar across groups. Barriers to nutritional intake and physical activity are common in cirrhosis and should be evaluated and treated in all patients. Asking simple screening questions in clinic and referring at-risk patients to expert multidisciplinary providers is a reasonable strategy to address these barriers. Future research should evaluate techniques to overcome modifiable barriers and enhance enablers.

Paternal alcoholism, negative parenting, and the mediating role of marital satisfaction

PubMed Central

Kachadourian, Lorig K.; Eiden, Rina D.; Leonard, Kenneth E.

2013-01-01

Given the documented association between paternal alcoholism and negative parenting behaviors, the purpose of this study was to examine longitudinally whether marital satisfaction mediates this relationship. Participants consisted of 197 families (102 without an alcoholic father, 95 with an alcoholic father) who were assessed at three time points: when children were 12, 24, and 36 months old. Results indicated that paternal alcoholism at 12 months was associated with decreased marital satisfaction at 24 months for both mothers and fathers. Marital satisfaction at 24 months in turn was associated with decreases in parental warmth and sensitivity at 36 months. Furthermore, marital satisfaction mediated the association between paternal alcoholism and parental warmth and sensitivity for both mothers and fathers. The implications of these findings for interventions for alcoholic families are discussed. PMID:19541430

Are different cut-off values of liver stiffness assessed by transient elastography according to the etiology of liver cirrhosis for predicting significant esophageal varices?

PubMed

Sporea, Ioan; Raţiu, Iulia; Bota, Simona; Şirli, Roxana; Jurchiş, Ana

2013-06-01

To determine if liver stiffness (LS) measurements by means of Transient Elastography (TE) vary according to the etiology of the underlying liver cirrhosis and to find if there are different TE cut-off values able to predict the presence of significant EV in alcoholic vs. viral etiology of cirrhosis. This retrospective study included patients diagnosed with liver cirrhosis of viral or alcoholic etiology. All patients were evaluated by means of TE (FibroScan) and upper gastrointestinal endoscopy. We performed 10 LS measurements in each patient and a median value expressed in kiloPascals (kPa) was calculated. Only those with a SR >/= 60% and an IQR<30% were considered as reliable MS measurements. According to the presence of EV the patients were divided in two categories: without significant EV and patients with significant EV (at least grade 2). The study included 697 cirrhotic patients with reliable LS measurements. The median LS values assessed by TE were significantly higher in cirrhotic patients with alcoholic etiology as compared with those with viral etiology of liver disease: 41 kPa vs. 21.1 kPa, p<0.0001. In the entire cohort of cirrhotic patients, LS assessed by means of TE for a cut-off value >29.5 kPa, had 77.5% sensitivity and 86.9% specificity for predicting the presence of significant EV (AUROC=0.871). The best LS cut-off value for predicting the presence of significant EV was higher in alcoholic cirrhosis as compared with those with viral etiology of liver cirrhosis: 32.5 kPa (AUROC=0.836) vs. 24.8 kPa (AUROC=0.867). LS cut-off values assessed by TE for predicting significant EV are significantly higher in patients with alcoholic cirrhosis as compared with patients with liver cirrhosis of viral etiology.

Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers.

PubMed Central

Lettéron, P; Duchatelle, V; Berson, A; Fromenty, B; Fisch, C; Degott, C; Benhamou, J P; Pessayre, D

1993-01-01

Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease. PMID:8472992

Attachment and alcohol use amongst athletes: the mediating role of conscientiousness and alexithymia.

PubMed

Andres, Fanny; Castanier, Carole; Le Scanff, Christine

2014-02-01

The present study aims to explore the mediating effects of conscientiousness and alexithymia in the relationship between parental attachment style and alcohol use in a large sample of athletic young people. Participants included 434 French sport sciences students. Alcohol use, parental attachment style, conscientiousness and alexithymia were assessed. The hypotheses were tested by using regression and bootstrapping mediation analyses. Maternal insecure attachment style is positively associated with alcohol use. The current study highlights a multiple pathway in this relationship. The results reveal the mediating effect of low conscientiousness and alexithymia between maternal insecure attachment and alcohol use. Athletes' alcohol use seems to be the result of a complex association of underlying psychological factors. © 2013.

Delta Opioid Pharmacology in Relation to Alcohol Behaviors

PubMed Central

Alongkronrusmee, Doungkamol; Chiang, Terrance

2016-01-01

Delta opioid receptors (DORs) are heavily involved in alcohol-mediated processes in the brain. In this chapter we provide an overview of studies investigating how alcohol directly impacts DOR pharmacology and of early studies indicating DOR modulation of alcohol behavior. We will offer a brief summary of the different animal species used in alcohol studies investigating DORs followed by a broader overview of the types of alcohol behaviors modulated by DORs. We will highlight a small set of studies investigating the relationship between alcohol and DORs in analgesia. We will then provide an anatomical overview linking DOR expression in specific brain regions to different alcohol behaviors. In this section, we will provide two models that try to explain how endogenous opioids acting at DORs may influence alcohol behaviors. Next, we will provide an overview of studies investigating certain new aspects of DOR pharmacology, including the formation of heteromers and biased signaling. Finally, we provide a short overview of the genetics of the DORs in relation to alcohol use disorders (AUDs) and a short statement on the potential of using DOR-based therapeutics for treatment of AUDs. PMID:27316912

Work-family conflict and alcohol use: examination of a moderated mediation model.

PubMed

Wolff, Jennifer M; Rospenda, Kathleen M; Richman, Judith A; Liu, Li; Milner, Lauren A

2013-01-01

Research consistently documents the negative effects of work-family conflict; however, little research focuses on alcohol use. This study embraces a tension reduction theory of drinking, wherein alcohol use is thought to reduce the negative effects of stress. The purpose of the study was to test a moderated mediation model of the relationship between work-family conflict and alcohol use in a Chicagoland community sample of 998 caregivers. Structural equation models showed that distress mediated the relationship between work-family conflict and alcohol use. Furthermore, tension reduction expectancies of alcohol exacerbated the relationship between distress and alcohol use. The results advance the study of work-family conflict and alcohol use, helping explain this complicated relationship using sophisticated statistical techniques. Implications for theory and practice are discussed.

Policy options for prevention: the case of alcohol.

PubMed

Toomey, T L; Wagenaar, A C

1999-01-01

Reducing the availability of alcohol through alcohol control policies such as excise taxes and the minimum legal drinking age has been effective in reducing a wide range of alcohol-related problems, including traffic crashes, liver cirrhosis, and violence. Alcohol control policies may be classified into two overlapping categories--public and institutional policies. Some policies such as alcohol server training may be either mandated by governmental jurisdictions or voluntarily adopted by individual institutions, which include alcohol retail establishments, other businesses, worksites, schools, colleges/universities, law enforcement agencies, religious institutions, insurance agencies, and alcohol producers. Public policies may be mandated by national, state/provincial, or local governments to regulate where, when, and how alcohol is sold and consumed. This paper describes the wide array of public and institutional policies available to reduce alcohol-related problems. Summaries of research evaluating specific alcohol control policies are provided when available.

Mediators of the relationship between religiousness/spirituality and alcohol problems in an adult community sample.

PubMed

Drerup, Michelle L; Johnson, Thomas J; Bindl, Stephen

2011-12-01

Johnson et al. (2008b) reported that, in a college student sample, the effect of religiousness on alcohol use was mediated by negative beliefs about alcohol, social influences, and spiritual well-being, and that these variables in turn impacted alcohol use and problems both directly and indirectly via motives for drinking. This study attempted to replicate those findings in a sample of community dwelling adults (N=211). The effect of Religious/Spiritual Involvement was mediated by Negative Beliefs about Alcohol, Social Modeling, and Spiritual-Well-Being. However, Social Modeling had stronger relationships with motives for drinking and alcohol consumption than the other two mediators. The effect of Religious Struggle on Alcohol Problems was mediated by Spiritual Well-Being and coping motives for drinking. Results provide further support for the motivational model of alcohol use and suggest plausible mechanisms by which religiousness could causally impact alcohol use and problems. Religious struggle may be a clinically significant correlate of alcohol problems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mediators and moderators of parental alcoholism effects on offspring self-esteem.

PubMed

Rangarajan, Sripriya

2008-01-01

The goal of the proposed study was fourfold: (i) to examine the effects of parental alcoholism on adult offspring's self-esteem; (ii) to identify and test possible mediators and moderators of parental alcoholism effects on the self-esteem of adult offspring; (iii) to examine the utility and relevance of attachment theory (Bowlby J. (1969) Attachment and Loss: Vol. 1. Attachment. New York: Basic Books) in explaining parental alcoholism effects on self-esteem and (iv) to address some of the methodological limitations identified in past research on adult children of alcoholics (ACOA). Participants (N = 515) completed retrospective reports of parental alcoholism, family stressors, family communication patterns, parental attachment and a current measure of self-esteem. The results showed support for the detrimental effects of parental alcoholism on offspring self-esteem and offered partial support for family stressors as a mediator of parental alcoholism effects on parental attachment and parental attachment as a mediator of parental alcoholism effects on offspring self-esteem, respectively. Finally, support was found for family communication patterns as a moderator of the effects of family stressors on attachment. The study findings offer preliminary support for the utility of attachment theory in explicating parental alcoholism effects on the self-esteem of adult offspring. Findings from the present study make salient the need to consider factors beyond the identification of parental alcohol abuse when explicating individual differences in offspring self-esteem in adulthood. The identification of protective and risk factors can contribute to the development of optimal intervention strategies to help ACOAs better than simply the knowledge of family drinking patterns.

Parental Physical Force and Alcohol Use in Emerging Adults: Mediation by Psychological Problems.

PubMed

Pollard, Mary Ward; McKinney, Cliff

2016-07-01

Research has indicated that negative parenting practices, such as physical punishment, are associated with negative outcomes in children. These negative outcomes can present during childhood and during emerging adulthood. One negative consequence can be excessive alcohol use, a problematic outcome with its own myriad consequences. The goal of the current study was to examine the effects of parental physical force on emerging adult functioning, specifically alcohol and psychological problems. A sample of 488 young adults completed questionnaires on current perceptions related to alcohol-related problems, physical and psychological aggression by their parents experienced during the previous year, and current emotional and behavioral functioning. Results showed full mediation between paternal physical force and emerging adult alcohol problems by emerging adult psychological problems. Emerging adult psychological problems partially mediated the effect of maternal physical force on emerging adult alcohol problem. Gender did not moderate these effects. The results support existing literature suggesting that the use of parental physical force may lead to a chain reaction of problems, even during emerging adulthood. These results also reveal that emerging adults report currently receiving physical force from their parents, which brings to light a concerning lack of literature on the use of parental physical force on emerging adult children. These results advocate for positive parenting practives and efforts to teach them, even for emerging adult children. The results may also clinically suggest that paying attention to parental force in emerging adult clients could yield a better understanding of their current functioning, especially including excessive alcohol use.

Prevalence of Cirrhosis in Patients with Thrombocytopenia Who Receive Bone Marrow Biopsy

PubMed Central

Sheikh, Muhammad Y.; Raoufi, Rahim; Atla, Pradeep R.; Riaz, Muhammad; Oberer, Chad; Moffett, Michael J.

2012-01-01

Background/Aim: Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM) biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown. Materials and Methods: Between fiscal years 2006-2010, 744 patients (≥18 years) who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study. Results: Of 203 patients, 136 (67%) had a normal and 67 (33%) had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9). 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001). Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH) (47%), followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI) (33.4 vs. 25.8, P < 0.001) and lower MELD scores (11.1 vs. 16, P = 0.028) when compared to non-NASH patients with cirrhosis. Conclusion: Approximately, one third (35%) of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia. PMID:22824769

Work-family Conflict and Alcohol Use: Examination of a Moderated Mediation Model

PubMed Central

Wolff, Jennifer M.; Rospenda, Kathleen M.; Richman, Judith A.; Liu, Li; Milner, Lauren A.

2013-01-01

Research consistently documents the negative effects of work-family conflict; however, little focuses on alcohol use. This study embraces a tension-reduction theory of drinking, wherein alcohol use is thought to reduce the negative effects of stress. The purpose of the present study was to test a moderated mediation model of the relationship between work-family conflict and alcohol use in a Chicagoland community sample of 998 caregivers. Structural equation models showed that distress mediated the relationship between work-family conflict and alcohol use. Furthermore, tension reduction expectancies of alcohol exacerbated the relationship between distress and alcohol use. The results advance the study of work-family conflict and alcohol use, helping explain this complicated relationship using sophisticated statistical techniques. Implications for theory and practice are discussed. PMID:23480251

 High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2 diabetic patients.

PubMed

Arab, Juan P; Barrera, Francisco; Gallego, Consuelo; Valderas, Juan P; Uribe, Sergio; Tejos, Cristian; Serrano, Cristóbal; Serrano, Cristóbal; Huete, Álvaro; Liberona, Jessica; Labbé, Pilar; Quiroga, Teresa; Benítez, Carlos; Irarrázaval, Pablo; Riquelme, Arnoldo; Arrese, Marco

2016-01-01

 Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH), the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on prevalence of advanced fibrosis among T2DM patients is scarce. To evaluate prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive methods in T2DM patients. 145 consecutive T2DM patients (> 55 years-old) were prospectively recruited. Presence of cirrhosis and advanced fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis score (NFS) respectively. Exclusion criteria included significant alcohol consumption, markers of viral hepatitis infection or other liver diseases. Results are expressed in percentage or median (interquartile range). 52.6% of patients were women, the median age was 60 years old (57-64), mean BMI was 29.6 ± 4.7 kg/m2 and diabetes duration was 7.6 ± 6.9 years. A high prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%) and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were independently associated to advanced fibrosis. A high frequency of undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM patients. Screening of these conditions may be warranted in this patient population.

Insomnia severity as a mediator of the association between mental health symptoms and alcohol use in young adult veterans.

PubMed

Miller, Mary Beth; DiBello, Angelo M; Carey, Kate B; Borsari, Brian; Pedersen, Eric R

2017-08-01

Prior research has documented associations between mental health and alcohol use, mental health and insomnia, and insomnia and alcohol use. This study examined insomnia severity as a mediator of the association between mental health and alcohol-related outcomes in young adult veterans. Veterans aged 18-34 years (N=622, 83% male) who reported drinking in the past year completed assessments at baseline and one-month follow-up as part of a larger intervention trial. Participants reported symptoms of depression and posttraumatic stress disorder (PTSD) at baseline, insomnia severity at one month, and alcohol use and related consequences at baseline and one month. Mediation analyses using bootstrapped confidence intervals were used to examine the indirect effects of baseline mental health symptoms on alcohol-related outcomes at one month via insomnia severity. Insomnia severity was associated with both drinking quantity and alcohol-related consequences. Greater depressive (but not PTSD) symptoms were associated directly with more alcohol-related consequences. Neither depressive nor PTSD symptoms had direct effects on drinking quantity when controlling for the other mental health symptoms (e.g., depressive symptoms did not predict drinking quantity when controlling for symptoms of PTSD). However, symptoms of depression and PTSD predicted drinks per week and alcohol-related consequences indirectly through insomnia severity. Symptoms of depression and PTSD increase risk for alcohol use and related consequences in part by increasing symptoms of insomnia. Findings suggest that insomnia may be an appropriate target for prevention and intervention efforts among heavy-drinking Veterans reporting symptoms of depression or PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

Readiness to Change as a Mediator of the Effect of a Brief Motivational Intervention on Posttreatment Alcohol-Related Consequences of Injured Emergency Department Hazardous Drinkers

PubMed Central

Stein, L. A. R.; Minugh, P. Allison; Longabaugh, Richard; Wirtz, Philip; Baird, Janette; Nirenberg, Ted D.; Woolard, Robert F.; Carty, Kathy; Lee, Christina; Mello, Michael; Becker, Bruce; Gogineni, Aruna

2009-01-01

Brief motivational interventions (BMIs) are usually effective for reducing alcohol use and consequences in primary care settings. We examined readiness to change drinking as a mediator of the effects of BMI on alcohol-related consequences. Participants were randomized into three conditions: (a) standard care plus assessment (SC), (b) SC plus BMI (BI), and (c) BI plus a booster session (BIB). At 12-month follow-up BIB patients had significantly reduced alcohol consequences more than had SC patients. Patients receiving BI or BIB maintained higher readiness scores 3 months after treatment than did patients receiving SC. However, readiness mediated treatment effects only for those highly motivated to change prior to the intervention but not for those with low pre-intervention motivation. BI and BIB for these patients decreased alcohol consequences in part because they enhanced and maintained readiness for those highly motivated prior to the intervention, but not for those with low motivation. Results are opposite of what would be expected from MI theory. An alternative explanation is offered as to why this finding occurred with this opportunistically recruited Emergency Department patient population. PMID:19586135

Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of alcohol-related mortality in traumatic brain injury?

PubMed

Lai, Xiao-ping; Yu, Xiao-jun; Qian, Hong; Wei, Lai; Lv, Jun-yao; Xu, Xiao-hu

2013-01-01

Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in the EtOH-TBI group showed: (1) high mortality (50%, p < 0.01); (2) inhibited respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95 expression (p < 0.05). Chronic alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.

Do alcohol expectancies and peer delinquency/substance use mediate the relationship between impulsivity and drinking behaviour in adolescence?

PubMed

Barnow, Sven; Schultz, Gabriele; Lucht, Michael; Ulrich, Ines; Preuss, Ulrich-W; Freyberger, Harald-J

2004-01-01

To investigate (1). whether aggressive and delinquent behaviour problems predict subsequent adolescent drinking behaviour; and (2). to what extent this association is mediated by alcohol expectancies and/or peer delinquency/substance use. 147 adolescents (approximately 15 years old) were interviewed with regard to their drinking behaviour. In addition, several self-rating questionnaires were given to gather information regarding the peers of these children. As proposed by the Acquired Preparedness Model (APM), we found that behavioural problems were related to quantity and frequency of alcohol consumed, and that this relationship was mediated by alcohol expectancies. Regarding peer relations, we found positive correlations between drinking behaviour and peer delinquency/substance use, aggression/delinquency and alcohol expectancies. Furthermore, the association between behavioural problems and drinking decreased dramatically if peer delinquency/substance use was accounted for. A hierarchical regression analysis revealed that both alcohol expectancies and peer delinquency/substance use predicted alcohol consumption of adolescents at the 1-year follow-up above and beyond the effects of age, sex, family history of alcoholism and aggression/delinquency of respondents. Alcohol expectancies and peer delinquency/substance use are both crucial to the amount and frequency of adolescent alcohol use. They should be considered in designing prevention and intervention strategies in this age group.

[Alcohol].

PubMed

Zima, T

1996-07-14

Alcohol is one of the most widely used addictive substances. It can be assumed that everybody encounters alcohol--ethanol in various forms and concentrations in the course of their lives. A global and social problem of our civilization is alcohol consumption which has a rising trend. Since 1989 the consumption of alcoholic beverages is rising and the mean annual consumption of concentrated ethanol per head is cea 10 litres. In ethanol abuse the organism is damaged not only by ethanol alone but in particular by substances formed during its metabolism. Its detailed knowledge is essential for the knowledge and investigations of the metabolic and toxic effect of ethanol on the organism. Ingested alcohol is in 90-98% eliminated from the organism by three known metabolic pathways: 1-alcohol dehydrogenase, 2-the microsomal ethanol oxidizing system and 3-catalase. Alcohol is a frequent important risk factor of serious "diseases of civilization" such as IHD, hypertension, osteoporosis, neoplastic diseases. Cirrhosis of the liver and chronic pancreatitis are the well known diseases associated with alcohol ingestion and also their most frequent cause. It is impossible to list all organs and diseases which develop as a result of alcohol consumption. It is important to realize that regular and "relatively" small amounts in the long run damage the organism and may be even fatal.

THE RELATION BETWEEN DIFFERENT DIMENSIONS OF ALCOHOL CONSUMPTION AND BURDEN OF DISEASE - AN OVERVIEW

PubMed Central

Rehm, Jürgen; Baliunas, Dolly; Borges, Guilherme L. G.; Graham, Kathryn; lrving, Hyacinth; Kehoe, Tara; Parry, Charles D.; Patra, Jayadeep; Popova, Svetlana; Poznyak, Vladimir; Roerecke, Michael; Room, Robin; Samokhvalov, Andriy V.; Taylor, Benjamin

2012-01-01

AIMS As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: To evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries;To quantify relationships identified as causal based on published meta-analyses;To separate the impact on mortality vs. morbidity where possible; andTo assess the impact of the quality of alcohol on burden of disease. METHODS Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiologic criteria to determine causality. The extent of the risk relations was taken from meta-analyses. RESULTS Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications, foetal alcohol syndrome. Dose-response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were causally linked to IHD, foetal alcohol syndrome, and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ grams pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient

Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver function.

PubMed

García-Bañuelos, Jesús; Panduro, Arturo; Gordillo-Bastidas, Daniela; Gordillo-Bastidas, Elizabeth; Muñoz-Valle, José Francisco; Gurrola-Díaz, Carmen M; Sánchez-Enríquez, Sergio; Ruiz-Madrigal, Bertha; Bastidas-Ramírez, Blanca Estela

2012-03-01

Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico. Ninety C and 41 patients with AC were studied. Genotype and allele frequency were determined through polymerase chain reaction-restriction fragment length polymorphisms. Polymorphic allele distribution in AC was 1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and 10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited more decompensated liver functioning evaluated by total bilirubin and prothrombin time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed by Child's Pugh score and mortality, was higher in patients carrying the c2 allele, although not statistically significant. In this study, CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which could probably be attributed to the oxidative stress promoted by this polymorphic form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the development of alcohol-induced liver damage and its usefulness as a probable prognostic marker, should be performed. Also, increasing the number of patients and including a control group conformed by alcoholic patients free of liver damage may render more conclusive results. These findings contribute to the understanding of the influence of gene variations in AC development among populations, alcohol metabolism, and pharmacogenetics. Copyright © 2011 by the Research Society on Alcoholism.

Changes in the social class gradient of cirrhosis mortality in England and Wales across the 20th century.

PubMed

Crombie, Iain K; Precious, Elaine

2011-01-01

To explore the nature of the social class gradient of cirrhosis mortality in England and Wales across the 20th century. Data on male cirrhosis mortality by social class were obtained from the Registrar General's Decennial Supplements for the years 1921-1991. Data for 1941 were not collected because of the second World War. In 1921, cirrhosis mortality was substantially higher among the professional and managerial classes (I and II) than among the other social classes (III-V). This marked social class difference persisted until 1961 when the differences between the social classes were inconsistent. By 1991, the gradient had reversed and the lower social classes (IV and V) had the higher mortality. The excess mortality was greatest for social class V. The change in the mortality gradient is stark: in 1921social classes I and II had a cirrhosis mortality at least twice that of social classes IV and V, but by 1991 this ratio had reversed. The reversal in the social class gradient of cirrhosis mortality indicates a major change in risk factor distribution across social classes. Differential changes in alcohol consumption are a possible explanation for this change, although the 1991 social class gradient in cirrhosis is inconsistent with alcohol consumption data from national surveys. Further research is required to clarify the explanation for the observed gradient, so that appropriate preventive measures can be put into place.

Alcohol Outcome Expectancies and Regrettable Drinking-Related Social Behaviors

PubMed Central

Dunne, Eugene M.; Katz, Elizabeth C.

2015-01-01

Aims Research has shown that alcohol outcome expectancies are predictive of heavy alcohol consumption, which can lead to risky behavior. The purpose of the present study was to assess the incidence of various low-risk social behaviors while drinking among college students. Such social behaviors may later be regretted (referred to as regrettable social behaviors) and include electronic and in-person communications. Methods College students (N = 236) completed measures of alcohol outcome expectancies and regrettable social behaviors. Results Regrettable social behaviors were reported by 66.1% of participants, suggesting that they may occur at a much higher rate than more serious drinking-related consequences (e.g. drinking and driving, violence, etc.). Expectancies for social facilitation predicted regrettable social behavior. Further, this relationship was mediated by amount of alcohol consumed. Conclusion Given the high incidence, regrettable social behaviors may be effective targets in alcohol prevention programming. PMID:25820611

Reduced impact of alcohol use on next-day tiredness in older relative to younger adults: A role for sleep duration.

PubMed

Lydon-Staley, David M; Ram, Nilam; Brose, Annette; Schmiedek, Florian

2017-11-01

Recent work has suggested that older adults may be less susceptible to the next-day effects of alcohol relative to younger adults. The effects of alcohol in younger adults may be mediated by sleep duration, but due to age differences in the contexts of alcohol use, this mediation process may not generalize to older adults. The present study examined age-group (younger vs. older adults) differences in how alcohol use influenced next-day tiredness during daily life. Reports of alcohol use, sleep duration, and next-day tiredness obtained on ∼101 days from 91 younger adults (ages 20-31 years) and 75 older adults (ages 65-80 years) were modeled using a multilevel, moderated mediation framework. Findings indicated that (a) greater-than-usual alcohol use was associated with greater-than-usual tiredness in younger adults only, (b) greater-than-usual alcohol use was associated with shorter-than-usual sleep duration in younger adults only, and (c) shorter-than-usual sleep duration was associated with greater tiredness in both younger and older adults. For the prototypical younger adult, a significant portion (43%) of the association between alcohol use and next-day tiredness could be explained assuming mediation through sleep duration, whereas there was no evidence of mediation for the prototypical older adult. Findings of age differences in the mediation process underlying associations among alcohol use, sleep, and tiredness provide insight into the mechanisms driving recent observations of reduced next-day effects of alcohol in older relative to younger adults. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Adolescent alcohol-related risk cognitions: the roles of social norms and social networking sites.

PubMed

Litt, Dana M; Stock, Michelle L

2011-12-01

The present study examined the impact of socially based descriptive norms on willingness to drink alcohol, drinker prototype favorability, affective alcohol attitudes, and perceived vulnerability for alcohol-related consequences within the Prototype Willingness model. Descriptive norms were manipulated by having 189 young adolescents view experimenter-created profile pages from the social networking site Facebook, which either showed older peers drinking or not. The results provided evidence that descriptive norms for alcohol use, as portrayed by Facebook profiles, significantly impact willingness to use, prototypes, attitudes toward use, and perceived vulnerability. A multiple mediation analysis indicated that prototypes, attitudes, and perceptions of use mediated the relationship between the content of the Facebook profile and willingness. These results indicate that adolescents who perceive that alcohol use is normative, as evidenced by Facebook profiles, are at higher risk for cognitions shown to predict alcohol use than adolescents who do not see alcohol use portrayed as frequently on Facebook.

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

Peer pressure and alcohol use in young men: a mediation analysis of drinking motives.

PubMed

Studer, Joseph; Baggio, Stéphanie; Deline, Stéphane; N'Goran, Alexandra A; Henchoz, Yves; Mohler-Kuo, Meichun; Daeppen, Jean-Bernard; Gmel, Gerhard

2014-07-01

Peer pressure (PP) has been shown to play a major role in the development and continuation of alcohol use and misuse. To date, almost all the studies investigating the association of PP with alcohol use only considered the PP for misconduct but largely ignored other aspects of PP, such as pressure for peer involvement and peer conformity. Moreover, it is not clear whether the association of PP with alcohol use is direct or mediated by other factors. The aim of the present study was to investigate the association of different aspects of peer pressure (PP) with drinking volume (DV) and risky single-occasion drinking (RSOD), and to explore whether these associations were mediated by drinking motives (DM). A representative sample of 5521 young Swiss men, aged around 20 years old, completed a questionnaire assessing their usual weekly DV, the frequency of RSOD, DM (i.e. enhancement, social, coping, and conformity motives), and 3 aspects of PP (i.e. misconduct, peer involvement, and peer conformity). Associations between PP and alcohol outcomes (DV and RSOD) as well as the mediation of DM were tested using structural equation models. Peer pressure to misconduct was associated with more alcohol use, whereas peer involvement and peer conformity were associated with less alcohol use. Associations of drinking outcomes with PP to misconduct and peer involvement were partially mediated by enhancement and coping motives, while the association with peer conformity was partially mediated by enhancement and conformity motives. Results suggest that PP to misconduct constitutes a risk factor, while peer conformity and peer involvement reflect protective factors with regard to alcohol use. Moreover, results from the mediation analyses suggest that part of the association of PP with alcohol use came indirectly through DM: PP was associated with DM, which in turn were associated with alcohol use. Copyright © 2014 Elsevier B.V. All rights reserved.

Emotion Dysregulation Facets as Mediators of the Relationship between PTSD and Alcohol Misuse

PubMed Central

Tripp, Jessica C.; McDevitt-Murphy, Meghan E.

2015-01-01

Introduction Posttraumatic stress disorder (PTSD) and alcohol misuse, which frequently co-occur among combat veterans, have been linked to emotion dysregulation. Emotion dysregulation may explain the link between PTSD and alcohol misuse, and this investigation tested emotion dysregulation as a mediator of that relationship. Method Correlations between PTSD symptoms and cluster symptoms, emotion dysregulation full and subscales, and alcohol misuse were examined in a sample of 139 combat Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans (45% African American; 89% men). Emotion dysregulation full scale and subscales were examined as mediators of the relationship between PTSD symptoms and alcohol misuse for the full sample and men only. Results PTSD symptoms and symptom clusters, emotion dysregulation, and alcohol misuse showed positive correlations for the full sample and men only. Neither the full scale of emotion dysregulation nor the facets of emotion dysregulation mediated the relationship between PTSD symptoms and alcohol misuse for the full sample; among men, the Impulse Control Difficulties when Upset and Lack of Emotional Clarity subscales were mediators of that relationship. Conclusions Impulse control difficulties and lack of emotional clarity may play an important role in the link between PTSD and alcohol misuse for male veterans and should be an important target in treatment for individuals with both disorders disorders. Addressing impulse control difficulties and lack of emotional clarity in those with PTSD and alcohol misuse may improve outcomes by helping individuals identify and describe upsetting emotions and develop healthy coping alternatives to alcohol misuse. PMID:25864136

HIV-related thought avoidance, sexual risk, and alcohol use among men who have sex with men.

PubMed

Pérez, Ashley E; Wray, Tyler B; Celio, Mark A; Monti, Peter M

2018-07-01

HIV-related "cognitive escape" refers to a tendency to avoid thoughts associated with HIV, which may be particularly common among men who have sex with men (MSM) who are often inundated with HIV information, potentially to the point of fatigue. HIV-related cognitive escape is associated with increased sexual risk behaviors, such as condomless sex, and heavier alcohol use patterns. Other studies show that some MSM may use alcohol specifically to facilitate sex. These sexual motives for drinking (SMDs) could be one mechanism whereby cognitive escape leads to health risk behaviors. In this study, we tested models exploring whether cognitive escape was associated with markers of sex risk (condom use, number of sex partners) and alcohol use/problems, and examined whether SMDs mediated these associations. Heavy drinking, HIV-negative men (N = 196) aged ≥ 21 years who self-reported past year condomless anal sex with men completed assessments as part of a larger study. Results suggest that cognitive escape was associated with higher number of anal sex partners (incidence rate ratio [IRR] = 1.50, SE = 0.04, p < .001), decreased condom use (B = -0.30, SE = 0.14, p = .028), and increased alcohol-related problems (IRR = 1.28, SE = 0.07, p = .001) but not with drinking quantity. Sexual motives for drinking appeared to partially mediate the observed relationship between cognitive escape and alcohol-related problems, but other relationships did not show evidence of mediation. Findings suggest that those who tend to avoid HIV-related thoughts may be at increased risk for HIV and alcohol-related problems. Drinking to facilitate sex may partially account for the higher risk for alcohol-related problems conferred by cognitive escape. Alcohol interventions for MSM may be more effective if they address alcohol's role in coping with HIV threat and in facilitating sex under these circumstances.

Depressive symptoms, ruminative thinking, drinking motives, and alcohol outcomes: A multiple mediation model among college students in three countries.

PubMed

Bravo, Adrian J; Pilatti, Angelina; Pearson, Matthew R; Mezquita, Laura; Ibáñez, Manuel I; Ortet, Generós

2018-01-01

Recent research suggests that ruminative thinking (specifically problem-focused thoughts) may explain why individuals engage in drinking to cope (DTC) when dealing with depressive symptoms; which in turn leads to increased negative alcohol-related consequences. Cross-cultural studies addressing these phenomena are scarce. The present study cross-culturally tested whether four rumination facets (problem-focused thoughts, counterfactual thinking, repetitive thoughts, and anticipatory thoughts) uniquely mediate the relationships between depressive symptoms and drinking motives/alcohol outcomes in a multicultural sample of college student drinkers (n=1429) from Spain, Argentina, and the U.S. Structural equation modeling was conducted to test the models, controlling for sex. Further, we conducted invariance testing to determine whether our models were culturally-specific or culturally-universal. Within both proposed models, no rumination facet uniquely mediated the relationship between depressive symptoms and drinking motives. However, an exploratory model with a second-order latent factor of ruminative thinking did significantly mediate these associations (exception was conformity motives). Further, there were two significant double-mediated associations that suggested that increased depressive symptoms is associated with increased ruminative thinking, which is associated with higher DTC motives, which in turn is associated with higher alcohol consumption and negative alcohol-related consequences. All models were found to be invariant across countries and sex, suggesting that these associations may be relatively universal. Rumination is relevant to understand the increased vulnerability of college drinkers to exhibit greater alcohol consumption and negative consequences via DTC motives when dealing with depressive symptoms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

PubMed

El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

2016-09-01

Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

Why is social network drinking associated with college students' alcohol use? Focus on psychological mediators.

PubMed

Reid, Allecia E; Carey, Kate B

2018-06-01

Level of drinking in the social network is strongly associated with college students' alcohol use. However, mechanisms through which networks are associated with personal drinking have been underexplored thus far. The present study examined theoretically derived constructs-sociability outcome expectancies, attitudes toward heavy drinking, self-efficacy for use of protective strategies, and descriptive norms-as potential mediators of the association between egocentric social network drinking and personal consumption. College students (N = 274) self-reported their social network's level of alcohol consumption, all mediators, drinks per week, and consequences at both baseline (Time 1) and a 1-month follow-up (Time 2). Autoregressive mediation models focused on the longitudinal associations between Time 1 network drinking and the Time 2 mediators and between the Time 1 mediators and the Time 2 outcomes. Consistent with hypotheses, Time 1 social network drinking was significantly associated with Time 2 drinks per week and consequences. Only attitudes significantly mediated social network associations with drinks per week and consequences, though the proportion of the total effects accounted for by attitudes was small. After accounting for the stability of constructs over time, social network drinking was generally un- or weakly related to sociability expectancies, self-efficacy, and descriptive norms. Results support reducing attitudes toward heavy drinking as a potential avenue for mitigating network effects, but also highlight the need to evaluate additional potential mechanisms of network effects. Intervention efforts that aim to address the social network have the potential to substantially reduce alcohol consumption, thereby enhancing the overall efficacy of alcohol risk-reduction interventions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

[Liver cirrhosis mortality in Mexico. II. Excess mortality and pulque consumption].

PubMed

Narro-Robles, J; Gutiérrez-Avila, J H; López-Cervantes, M; Borges, G; Rosovsky, H

1992-01-01

Over the years high cirrhosis mortality rates have been reported in Mexico City and in the surrounding states (Hidalgo, Tlaxcala, Puebla and the State of Mexico); on the contrary, well defined areas, such as the northern states, have shown a considerably lower mortality rate. This situation may indicate that some factors such as the pattern of alcoholic intake and other environmental characteristics could explain this striking difference. To determine the role of alcohol, the availability and consumption of alcohol at regional and state level were compared with cirrhosis mortality rates. A high and statistically significant correlation was found with pulque availability and consumption (r = 72-92%, p less than 0.01) in all periods of time under examination. On the contrary, a statistically significant negative association was observed with beer consumption and a positive, but not significant correlation, with distilled alcoholic beverages. Infectious hepatitis incidence, prevalence of exclusive use of native languages (as an indirect index of ethnic background) and nutritional deficiencies were also studied as possible risk factors. Nutritional deficiencies and the prevalence of exclusive use of náhuatl and otomí languages were positively correlated. These results can be useful to conduct further epidemiological studies still needed to determine the etiologic role of pulque consumption as well as of the other risk factors. Nonetheless, the current data stress the need to implement public health programs to reduce alcohol consumption, especially pulque, and to minimize the impact of these risk factors in high mortality areas.

Dyadic conflict, drinking to cope, and alcohol-related problems: A psychometric study and longitudinal actor-partner interdependence model.

PubMed

Lambe, Laura; Mackinnon, Sean P; Stewart, Sherry H

2015-10-01

The motivational model of alcohol use posits that individuals may consume alcohol to cope with negative affect. Conflict with others is a strong predictor of coping motives, which in turn predict alcohol-related problems. Two studies examined links between conflict, coping motives, and alcohol-related problems in emerging adult romantic dyads. It was hypothesized that the association between conflict and alcohol-related problems would be mediated by coping-depression and coping-anxiety motives. It was also hypothesized that this would be true for actor (i.e., how individual factors influence individual behaviors) and partner effects (i.e., how partner factors influence individual behaviors) and at the between- (i.e., does not vary over the study period) and within-subjects (i.e., varies over the study period) levels. Both studies examined participants currently in a romantic relationship who consumed ≥12 alcoholic drinks in the past year. Study 1 was cross-sectional using university students (N = 130 students; 86.9% female; M = 21.02 years old, SD = 3.43). Study 2 used a 4-wave, 4-week longitudinal design with romantic dyads (N = 100 dyads; 89% heterosexual; M = 22.13 years old, SD = 5.67). In Study 2, coping-depression motives emerged as the strongest mediator of the conflict-alcohol-related problems association, and findings held for actor effects but not partner effects. Supplemental analyses revealed that this mediational pathway only held among women. Within any given week, alcohol-related problems changed systematically in the same direction between romantic partners. Interventions may wish to target coping-depression drinking motives within couples in response to conflict to reduce alcohol-related problems. (c) 2015 APA, all rights reserved).

Effect of obstructive sleep apnea on the sleep architecture in cirrhosis.

PubMed

Kappus, Matthew R; Leszczyszyn, David J; Moses, Leonard; Raman, Shekar; Heuman, Douglas M; Bajaj, Jasmohan S

2013-03-15

Sleep disturbances in cirrhosis are assumed to be due to hepatic encephalopathy (HE). The interaction between cirrhosis, prior HE, and obstructive sleep apnea (OSA) has not been evaluated. We aimed to evaluate the additional effect of cirrhosis with and without prior HE on the sleep architecture and perceived sleep disturbances of OSA patients. A case-control review of OSA patients who underwent polysomnography (PSG) in a liver-transplant center was performed. OSA patients with cirrhosis (with/without prior HE) were age-matched 1:1 with OSA patients without cirrhosis. Sleep quality, daytime sleepiness, sleep quality, and sleep architecture was compared between groups. Forty-nine OSA cirrhotic patients (age 57.4 ± 8.3 years, model for end-stage liver disease (MELD) 8.3 ± 5.4, 51% HCV, 20% prior HE) were age-matched 1:1 to OSA patients without cirrhosis. Apnea-hypopnea index, arousal index, sleep efficiency, daytime sleepiness, and effect of sleepiness on daily activities were similar between OSA patients with/ without cirrhosis. Sleep architecture, including %slow wave sleep (SWS), was also not different between the groups. MELD was positively correlated with time in early (N1) stage (r = 0.4, p = 0.03). All prior HE patients (n = 10) had a shift of the architecture towards early, non-restorative sleep (higher % [N2] stage [66 vs 52%, p = 0.005], lower % SWS [0 vs 29%, p = 0.02], lower REM latency [95 vs 151 minutes, p = 0.04]) compared to the rest. Alcoholic etiology was associated with higher latency to N1/N2 sleep, but no other effect on sleep architecture was seen. OSA can contribute to sleep disturbance in cirrhosis and should be considered in the differential of sleep disturbances in cirrhosis. Prior HE may synergize with OSA in worsening the sleep architecture.

Micro-RNA Profiling in Human Serum Reveals Compartment-Specific Roles of miR-571 and miR-652 in Liver Cirrhosis

PubMed Central

Roderburg, Christoph; Mollnow, Tobias; Bongaerts, Brenda; Elfimova, Natalia; Vargas Cardenas, David; Berger, Katharina; Zimmermann, Henning; Koch, Alexander; Vucur, Mihael; Luedde, Mark; Hellerbrand, Claus; Odenthal, Margarete; Trautwein, Christian; Tacke, Frank; Luedde, Tom

2012-01-01

Background and Aims Micro-RNAs (miRNAs) have recently emerged as crucial modulators of molecular processes involved in chronic liver diseases. The few miRNAs with previously proposed roles in liver cirrhosis were identified in screening approaches on liver parenchyma, mostly in rodent models. Therefore, in the present study we performed a systematic screening approach in order to identify miRNAs with altered levels in the serum of patients with chronic liver disease and liver cirrhosis. Methods We performed a systematic, array-based miRNA expression analysis on serum samples from patients with liver cirrhosis. In functional experiments we evaluated the relationship between alterations of miRNA serum levels and their role in distinct cellular compartments involved in hepatic cirrhosis. Results The array analysis and the subsequent confirmation by qPCR in a larger patient cohort identified significant alterations in serum levels of miR-513-3p, miR-571 and miR-652, three previously uncharacterized miRNAs, in patients with alcoholic or hepatitis C induced liver cirrhosis. Of these, miR-571 serum levels closely correlated with disease stages, thus revealing potential as a novel biomarker for hepatic cirrhosis. Further analysis revealed that up-regulation of miR-571 in serum reflected a concordant regulation in cirrhotic liver tissue. In isolated primary human liver cells, miR-571 was up-regulated in human hepatocytes and hepatic stellate cells in response to the pro-fibrogenic cytokine TGF-β. In contrast, alterations in serum levels of miR-652 were stage-independent, reflecting a concordant down-regulation of this miRNA in circulating monocytes of patients with liver cirrhosis, which was inducible by proinflammatory stimuli like bacterial lipopolysaccharide. Conclusion Alterations of miR571 and miR-652 serum levels in patients with chronic liver disease reflect their putative roles in the mediation of fibrogenic and inflammatory processes in distinct cellular

Avoidance of alcohol-related stimuli in alcohol-dependent inpatients.

PubMed

Townshend, J M; Duka, T

2007-08-01

Previous research has shown an attentional bias toward drug-related stimuli in heavy social drinkers. Attentional orientation to drug-related cues may lead to increased craving and preoccupation with the drug and impaired ability to focus attention on nondrug-related activities, resulting in renewed drug taking or relapse from drug abstinence. The aim of this study was to investigate whether alcohol-dependent inpatients would differ in their selective attention toward alcohol-related stimuli in comparison with a group of social drinking controls. Thirty-five alcohol-dependent inpatients were compared with a group of 39 social drinking controls matched for age, sex, and verbal IQ. Attentional bias was assessed using alcohol-related pictures in a dot probe detection task. Questionnaires were used to examine outcome expectancies after alcohol consumption, anxiety, mood, and craving. The alcoholic inpatients showed a bias away from the alcohol-related stimuli, scored higher on alcohol outcome expectancies, and on anxiety measures (both state and trait). They also presented with more negative mood compared with the control group. Craving was higher in the alcoholic group for the factor "loss of control over drinking." Alcoholic inpatients undergoing treatment based on the 12-step treatment of Alcoholics Anonymous (Minnesota model), which includes counseling, and intensive group, individual, and family psychotherapy, show an avoidance for drug-related stimuli and a perception of loss of control over drinking. We suggest that their increased perception of loss of control over drinking produces the avoidance from the drug-related stimuli.

Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

PubMed

Eriksson, C J P; Etelälahti, T J; Apter, S J

2017-06-01

A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational

Do Alcohol Expectancy Outcomes and Valuations Mediate Peer Influences and Lifetime Alcohol Use among Early Adolescents?

ERIC Educational Resources Information Center

Zamboanga, Byron L.; Schwartz, Seth J.; Ham, Lindsay S.; Jarvis, Lorna Hernandez; Olthuis, Janine V.

2009-01-01

Building on the theory of reasoned action (I. Ajzen & M. Fishbein, 1973, 1980; M. Fishbein & I. Ajzen, 1975) and expectancy theory, the authors examined the mediating role of alcohol expectancies in adolescent drinking behaviors by testing whether alcohol expectancy outcomes and valuations (the extent to which these outcomes are perceived…

Liver Cirrhosis is Independently Associated With 90-Day Mortality in ARDS Patients.

PubMed

Gacouin, Arnaud; Locufier, Maxime; Uhel, Fabrice; Letheulle, Julien; Bouju, Pierre; Fillatre, Pierre; Le Tulzo, Yves; Tadié, Jean Marc

2016-01-01

In a few studies, cirrhosis has been associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). These studies were, however, conducted mostly before 2000. Over the last 15 years, the prognosis of cirrhotic patients admitted to the intensive care unit (ICU) seems to have improved and major changes in the management of mechanical ventilation (MV) of ARDS have appeared. The aim of this study was to determine whether cirrhosis remains a factor for poor prognosis despite improvements in MV techniques and supportive therapies for ARDS. Retrospective analysis of data recorded from 232 patients (42 with cirrhosis and 290 without cirrhosis) who received lung-protective ventilation for ARDS defined according to American-European Consensus Conference criteria and admitted from 2006 to 2013. Alcohol was the most common aetiology of the cirrhosis. The end point was mortality at day-90 from the diagnosis of ARDS, survival was calculated using the Kaplan-Meier method, and we used a Cox-proportional hazard model to determine whether cirrhosis remained independently associated with mortality after adjustment for other prognostic variables for ARDS described previously. Organ dysfunctions were assessed based on the Sequential Organ Failure Assessment (SOFA) criteria, pulmonary and nonpulmonary dysfunctions were distinguished and compared between cirrhotic and non-cirrhotic patients on the first 3 days of VM. Comparison of survival curves showed that cirrhotic patients had a poorer 90-day prognosis than non-cirrhotic patients (P = 0.03 by the log-rank test). After adjusted analysis, cirrhosis remained independently associated with mortality at day 90 (adjusted hazard ratio 2.09, 95% CI, 1.27-3.45, P = 0.004). Non-pulmonary SOFA scores were significantly higher in cirrhotic patients than in non-cirrhotic patients on day 1 (P < 0.001), day 2 (P = 0.003), and day 3 (P = 0.002) of MV for ARDS whereas pulmonary SOFA scores did not

Problem Drinking, Alcohol-Related Violence, and Homelessness among Youth Living in the Slums of Kampala, Uganda.

PubMed

Swahn, Monica H; Culbreth, Rachel; Tumwesigye, Nazarius Mbona; Topalli, Volkan; Wright, Eric; Kasirye, Rogers

2018-05-24

This paper examines problem drinking, alcohol-related violence, and homelessness among youth living in the slums of Kampala—an understudied population at high-risk for both alcohol use and violence. This study is based on a cross-sectional survey conducted in 2014 with youth living in the slums and streets of Kampala, Uganda ( n = 1134), who were attending Uganda Youth Development Link drop-in centers. The analyses for this paper were restricted to youth who reported current alcohol consumption ( n = 346). Problem drinking patterns were assessed among youth involved in alcohol-related violence. Mediation analyses were conducted to examine the impact of homelessness on alcohol-related violence through different measures of problem drinking. Nearly 46% of youth who consumed alcohol were involved in alcohol-related violence. Problem drinkers were more likely to report getting in an accident (χ² = 6.8, df = 1, p = 0.009), having serious problems with parents (χ² = 21.1, df = 1, p < 0.0001) and friends (χ² = 18.2, df = 1, p < 0.0001), being a victim of robbery (χ² = 8.8, df = 1, p = 0.003), and going to a hospital (χ² = 15.6, df = 1, p < 0.0001). For the mediation analyses, statistically significant models were observed for frequent drinking, heavy drinking, and drunkenness. Interventions should focus on delaying and reducing alcohol use in this high-risk population.

Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis Undergoing Non-Hepatic Surgeries

PubMed Central

Hemida, Khalid; Shabana, Sherif Sadek; Said, Hani; Ali-Eldin, Fatma

2016-01-01

Introduction Patients with chronic liver diseases are at great risk for both morbidity and mortality during the post-operative period due to the stress of surgery and the effects of general anaesthesia. Aim The main aim of this study was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post-operative mortality in Egyptian patients with liver cirrhosis undergoing non-hepatic surgery under general anaesthesia. Materials and Methods A total of 60 patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in this study. Sensitivity and specificity of MELD and CTP scores were evaluated for the prediction of post-operative mortality. A total of 20 patients who had no clinical, biochemical or radiological evidence of liver disease were included to serve as a control group. Results The highest sensitivity and specificity for detection of post-operative mortality was detected at a MELD score of 13.5. CTP score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy of 95% for prediction of post-operative mortality. On the other side and at a cut-off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%, and an overall accuracy of 66.6% for prediction of post-operative mortality in patients with HCV- related liver cirrhosis. Conclusion MELD score proved to be more sensitive but less specific than CTP score for prediction of post-operative mortality. CTP and MELD scores may be complementary rather than competitive in predicting post-operative mortality in patients with HCV- related liver cirrhosis. PMID:27891371

Effect of Obstructive Sleep Apnea on the Sleep Architecture in Cirrhosis

PubMed Central

Kappus, Matthew R.; Leszczyszyn, David J.; Moses, Leonard; Raman, Shekar; Heuman, Douglas M.; Bajaj, Jasmohan S.

2013-01-01

Study Objectives: Sleep disturbances in cirrhosis are assumed to be due to hepatic encephalopathy (HE). The interaction between cirrhosis, prior HE, and obstructive sleep apnea (OSA) has not been evaluated. We aimed to evaluate the additional effect of cirrhosis with and without prior HE on the sleep architecture and perceived sleep disturbances of OSA patients. Methods: A case-control review of OSA patients who underwent polysomnography (PSG) in a liver-transplant center was performed. OSA patients with cirrhosis (with/without prior HE) were age-matched 1:1 with OSA patients without cirrhosis. Sleep quality, daytime sleepiness, sleep quality, and sleep architecture was compared between groups. Results: Forty-nine OSA cirrhotic patients (age 57.4 ± 8.3 years, model for end-stage liver disease (MELD) 8.3 ± 5.4, 51% HCV, 20% prior HE) were age-matched 1:1 to OSA patients without cirrhosis. Apnea-hypopnea index, arousal index, sleep efficiency, daytime sleepiness, and effect of sleepiness on daily activities were similar between OSA patients with/ without cirrhosis. Sleep architecture, including %slow wave sleep (SWS), was also not different between the groups. MELD was positively correlated with time in early (N1) stage (r = 0.4, p = 0.03). All prior HE patients (n = 10) had a shift of the architecture towards early, non-restorative sleep (higher % [N2] stage [66 vs 52%, p = 0.005], lower % SWS [0 vs 29%, p = 0.02], lower REM latency [95 vs 151 minutes, p = 0.04]) compared to the rest. Alcoholic etiology was associated with higher latency to N1/N2 sleep, but no other effect on sleep architecture was seen. Conclusions: OSA can contribute to sleep disturbance in cirrhosis and should be considered in the differential of sleep disturbances in cirrhosis. Prior HE may synergize with OSA in worsening the sleep architecture. Citation: Kappus MR; Leszczyszyn DJ; Moses L; Raman S; Heuman DM; Bajaj JS. Effect of obstructive sleep apnea on the sleep architecture in cirrhosis

Alcohol expectancies and social self-efficacy as mediators of differential intervention outcomes for college hazardous drinkers with social anxiety.

PubMed

Black, Jessica J; Tran, Giao Q; Goldsmith, Abigail A; Thompson, Rachel D; Smith, Joshua P; Welge, Jeffrey A

2012-03-01

The current pilot study examined the roles of two cognitive factors - positive alcohol expectancies of social anxiety reduction and drink refusal self-efficacy relevant to social situations - in mediating greater reduction in alcohol behaviors by the Brief Intervention for Socially Anxious Drinkers (BISAD; n=21) compared to an alcohol psychoeducation (n=20) in a sample of college hazardous drinkers with social anxiety. Mediation analysis results indicated that decreased positive alcohol expectancies and increased drink refusal self-efficacy relevant to social situations accounted for an average of 67% of the variance in treatment outcomes as measured by total quantity of alcohol consumption, heavy drinking days and problems related to alcohol use in the past month. Study results may enhance the understanding of cognitive factors' role in alcohol treatment outcomes, which could in turn improve the efficacy of interventions aimed to reduce hazardous drinking and comorbid social anxiety. Copyright © 2011 Elsevier Ltd. All rights reserved.

Poor adjustment to college life mediates the relationship between drinking motives and alcohol consequences: a look at college adjustment, drinking motives, and drinking outcomes.

PubMed

LaBrie, Joseph W; Ehret, Phillip J; Hummer, Justin F; Prenovost, Katherine

2012-04-01

The current study examined whether the relationship between drinking motives and alcohol-related outcomes was mediated by college adjustment. Participants (N=253) completed an online survey that assessed drinking motives, degree of both positive and negative college adjustment, typical weekly drinking, and past month negative alcohol-related consequences. Structural equation modeling examined negative alcohol consequences as a function of college adjustment, drinking motives, and weekly drinking behavior in college students. Negative college adjustment mediated the relationship between coping drinking motives and drinking consequences. Positive college adjustment was not related to alcohol consumption or consequences. Positive reinforcement drinking motives (i.e. social and enhancement) not only directly predicted consequences, but were partially mediated by weekly drinking and degree of negative college adjustment. Gender specific models revealed that males exhibited more variability in drinking and their positive reinforcement drinking motives were more strongly associated with weekly drinking. Uniquely for females, coping motives were directly and indirectly (via negative adjustment) related to consequences. These findings suggest that interventions which seek to decrease alcohol-related risk may wish to incorporate discussions about strategies for decreasing stress and increasing other factors associated with better college adjustment. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Causes of the people death from drunkenness and alcoholism].

PubMed

Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

2012-01-01

We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

The Role of Therapeutic Endoscopy in Patients With Cirrhosis-Related Causes of Gastrointestinal Bleeding.

PubMed

Kezer, Camille A; Gupta, Neil

2018-06-09

This article aims to review current therapeutic endoscopic treatments available for the management of gastrointestinal bleeding related to cirrhosis. Endoscopic band ligation is an effective treatment for primary prophylaxis, acute bleeding, and secondary prophylaxis of esophageal varices as well as for acute bleeding and secondary prophylaxis of select gastric varices. Sclerotherapy is a treatment option for acute bleeding and secondary prophylaxis of esophageal varices when band ligation is technically difficult. Cyanoacrylate glue injection is an effective treatment for acute bleeding of gastric and ectopic varices. Argon plasma coagulation is first-line and radiofrequency ablation is second-line treatment for chronic bleeding secondary to gastric antral vascular ectasia. There are a variety of endoscopic treatment modalities for cirrhosis-related gastrointestinal bleeding, and the appropriate therapy depends on the location of the bleed, history or presence of acute bleeding, and risk factors for intervention-related adverse events.

Cooperative electrocatalytic alcohol oxidation with electron-proton-transfer mediators.

PubMed

Badalyan, Artavazd; Stahl, Shannon S

2016-07-21

The electrochemical oxidation of alcohols is a major focus of energy and chemical conversion efforts, with potential applications ranging from fuel cells to biomass utilization and fine-chemical synthesis. Small-molecule electrocatalysts for processes of this type are promising targets for further development, as demonstrated by recent advances in nickel catalysts for electrochemical production and oxidation of hydrogen. Complexes with tethered amines that resemble the active site of hydrogenases have been shown both to catalyse hydrogen production (from protons and electrons) with rates far exceeding those of such enzymes and to mediate reversible electrocatalytic hydrogen production and oxidation with enzyme-like performance. Progress in electrocatalytic alcohol oxidation has been more modest. Nickel complexes similar to those used for hydrogen oxidation have been shown to mediate efficient electrochemical oxidation of benzyl alcohol, with a turnover frequency of 2.1 per second. These compounds exhibit poor reactivity with ethanol and methanol, however. Organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl), are the most widely studied electrocatalysts for alcohol oxidation. These catalysts exhibit good activity (1–2 turnovers per second) with a wide range of alcohols and have great promise for electro-organic synthesis. Their use in energy-conversion applications, however, is limited by the high electrode potentials required to generate the reactive oxoammonium species. Here we report (2,2′-bipyridine)Cu/nitroxyl co-catalyst systems for electrochemical alcohol oxidation that proceed with much faster rates, while operating at an electrode potential a half-volt lower than that used for the TEMPO-only process. The (2,2′-bipyridine)Cu(II) and TEMPO redox partners exhibit cooperative reactivity and exploit the low-potential, proton-coupled TEMPO/TEMPOH redox process rather than the high-potential TEMPO/TEMPO+ process. The results show how

Cooperative electrocatalytic alcohol oxidation with electron-proton-transfer mediators

NASA Astrophysics Data System (ADS)

Badalyan, Artavazd; Stahl, Shannon S.

2016-07-01

The electrochemical oxidation of alcohols is a major focus of energy and chemical conversion efforts, with potential applications ranging from fuel cells to biomass utilization and fine-chemical synthesis. Small-molecule electrocatalysts for processes of this type are promising targets for further development, as demonstrated by recent advances in nickel catalysts for electrochemical production and oxidation of hydrogen. Complexes with tethered amines that resemble the active site of hydrogenases have been shown both to catalyse hydrogen production (from protons and electrons) with rates far exceeding those of such enzymes and to mediate reversible electrocatalytic hydrogen production and oxidation with enzyme-like performance. Progress in electrocatalytic alcohol oxidation has been more modest. Nickel complexes similar to those used for hydrogen oxidation have been shown to mediate efficient electrochemical oxidation of benzyl alcohol, with a turnover frequency of 2.1 per second. These compounds exhibit poor reactivity with ethanol and methanol, however. Organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl), are the most widely studied electrocatalysts for alcohol oxidation. These catalysts exhibit good activity (1-2 turnovers per second) with a wide range of alcohols and have great promise for electro-organic synthesis. Their use in energy-conversion applications, however, is limited by the high electrode potentials required to generate the reactive oxoammonium species. Here we report (2,2‧-bipyridine)Cu/nitroxyl co-catalyst systems for electrochemical alcohol oxidation that proceed with much faster rates, while operating at an electrode potential a half-volt lower than that used for the TEMPO-only process. The (2,2‧-bipyridine)Cu(II) and TEMPO redox partners exhibit cooperative reactivity and exploit the low-potential, proton-coupled TEMPO/TEMPOH redox process rather than the high-potential TEMPO/TEMPO+ process. The results show how

Dimensional Anxiety Mediates Linkage of GABRA2 Haplotypes With Alcoholism

PubMed Central

Enoch, Mary-Anne; Schwartz, Lori; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

2015-01-01

The GABAAα2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P α0.007, OR α2.1, Plains Indians: P α0.040, OR α1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety. PMID:16874763

Mental health, sleep quality, drinking motives, and alcohol-related consequences: a path-analytic model.

PubMed

Kenney, Shannon R; Lac, Andrew; Labrie, Joseph W; Hummer, Justin F; Pham, Andy

2013-11-01

Poor mental health, sleep problems, drinking motivations, and high-risk drinking are prevalent among college students. However, research designed to explicate the interrelationships among these health risk behaviors is lacking. This study was designed to assess the direct and indirect influences of poor mental health (a latent factor consisting of depression, anxiety, and stress) to alcohol use and alcohol-related consequences through the mediators of global sleep quality and drinking motives in a comprehensive model. Participants were 1,044 heavy-drinking college students (66.3% female) who completed online surveys. A hybrid structural equation model tested hypotheses involving relations leading from poor mental health to drinking motives and poorer global sleep quality to drinking outcomes. Results showed that poor mental health significantly predicted all four subscales of drinking motivations (social, coping, conformity, and enhancement) as well as poor sleep. Most of the drinking motives and poor sleep were found to explain alcohol use and negative alcohol consequences. Poor sleep predicted alcohol consequences, even after controlling for all other variables in the model. The hypothesized mediational pathways were examined with tests of indirect effects. This is the first study to assess concomitantly the relationships among three vital health-related domains (mental health, sleep behavior, and alcohol risk) in college students. Findings offer important implications for college personnel and interventionists interested in reducing alcohol risk by focusing on alleviating mental health problems and poor sleep quality.

Relative effects of heavy alcohol use and hepatitis C in decompensated chronic liver disease in a hospital inpatient population.

PubMed

Mankal, Pavan Kumar; Abed, Jean; Aristy, Jose David; Munot, Khushboo; Suneja, Upma; Engelson, Ellen S; Kotler, Donald P

2015-03-01

Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. 347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p < 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence. While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.

mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors

PubMed Central

Liu, F; Laguesse, S; Legastelois, R; Morisot, N; Ben Hamida, S; Ron, D

2017-01-01

Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels. Furthermore, we demonstrate that alcohol intake also blocks glycogen synthase kinase-3β (GSK-3β)-phosphorylation of CRMP-2, which results in elevated binding of CRMP-2 to microtubules and a concomitant increase in microtubule content. Finally, we show that systemic administration of the CRMP-2 inhibitor lacosamide, or knockdown of CRMP-2 in the NAc decreases excessive alcohol intake. These results suggest that CRMP-2 in the NAc is a convergent point that receives inputs from two signaling pathways, mTORC1 and GSK-3β, that in turn drives excessive alcohol-drinking behaviors. PMID:26952865

Associations of systemic sphingolipids with measures of hepatic function in liver cirrhosis are related to cholesterol.

PubMed

Krautbauer, Sabrina; Wiest, Reiner; Liebisch, Gerhard; Buechler, Christa

2017-07-01

Lipoprotein particles are composed of various lipid classes including cholesterol and sphingolipids, and are low in serum of patients with liver cirrhosis. Hepatic decompensation is associated with a further decline of lipoproteins. Aim of the present work was to evaluate whether ceramide and sphingomyelin species are similarly changed in patients with liver cirrhosis and whether these variations are related to systemic cholesterol levels. In a cohort of 45 patients suffering from liver cirrhosis, cholesteryl ester species and subsequently total cholesterol were identified to be negatively associated with model of end stage liver disease (MELD) score. Indeed, the negative correlations of ceramide (Cer) and sphingomyelin (SM) species with MELD score, bilirubin and anti-thrombin 3 were non-significant after adjustment for cholesterol. Cer/SM ratios of species with identical acyl chains were not related to Child-Pugh or MELD score indicating that both lipids are comparably changed. Further, cholesterol levels and concentrations of all sphingolipids measured were similar in systemic, hepatic vein and portal vein blood. Cholesterol and distinct sphingolipids were similar before and 3 months after insertion of a transjugular intrahepatic portosystemic shunt while hexosylceramide 24:1 was significantly induced. It is concluded that analysis of distinct systemic sphingolipid species is not superior to measurement of cholesterol as non-invasive marker of hepatic injury in patients with liver cirrhosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Autologous Peripheral Blood Stem Cell Transplantation Improves Portal Hemodynamics in Patients with Hepatitis B Virus-related Decompensated Cirrhosis.

PubMed

Deng, Qinzhi; Cai, Ting; Zhang, Shun; Hu, Airong; Zhang, Xingfen; Wang, Yinyin; Huang, Jianrong

2015-12-01

Chronic hepatitis B virus (HBV) infection may eventually lead to decompensated liver cirrhosis, which is a terminal illness. The aim of this study was to investigate the therapeutic efficacy of autologous peripheral blood stem cell (APBSC) transplantation to improve portal vein hemodynamics in patients with HBV-related decompensated cirrhosis. This prospective study included 68 hospitalized patients who were diagnosed with HBV-related decompensated cirrhosis. These patients were divided into two groups: the transplantation group included 33 patients, while the control group included 35. Both groups received conventional medical treatment simultaneously, and APBSC transplantation was performed on the patients in the transplantation group. We evaluated the effects of APBSC transplantation on postoperative liver function using the following indices: total bilirubin, serum prothrombin and albumin, spleen size, and portal vein hemodynamics. Postoperatively, all of the patients were followed up at 24, 36, and 48 weeks. The transplantation group had no serious reactions. Compared with the control group, albumin and prothrombin activity in the transplantation group was significantly improved at 24, 36, and 48 weeks after the procedure, and spleen length and portal vein diameter were substantially reduced at 48 weeks. The velocity of peak portal vein blood flow and mean maximum portal vein blood flow were greatly increased in the APBSC transplantation group at 36 and 48 weeks, respectively; however, there was also decreased portal vein diameter, which reduced portal vein pressure in patients with HBV-related decompensated cirrhosis. APBSC transplantation greatly benefits HBV-linked decompensated cirrhosis patients and should be recommended in clinical practice.

In Patients With Cirrhosis, Driving Simulator Performance Is Associated With Real-life Driving.

PubMed

Lauridsen, Mette M; Thacker, Leroy R; White, Melanie B; Unser, Ariel; Sterling, Richard K; Stravitz, Richard T; Matherly, Scott; Puri, Puneet; Sanyal, Arun J; Gavis, Edith A; Luketic, Velimir; Siddiqui, Muhammad S; Heuman, Douglas M; Fuchs, Michael; Bajaj, Jasmohan S

2016-05-01

Minimal hepatic encephalopathy (MHE) has been linked to higher real-life rates of automobile crashes and poor performance in driving simulation studies, but the link between driving simulator performance and real-life automobile crashes has not been clearly established. Furthermore, not all patients with MHE are unsafe drivers, but it is unclear how to distinguish them from unsafe drivers. We investigated the link between performance on driving simulators and real-life automobile accidents and traffic violations. We also aimed to identify features of unsafe drivers with cirrhosis and evaluated changes in simulated driving skills and MHE status after 1 year. We performed a study of outpatients with cirrhosis (n = 205; median 55 years old; median model for end-stage liver disease score, 9.5; none with overt hepatic encephalopathy or alcohol or illicit drug use within previous 6 months) seen at the Virginia Commonwealth University and McGuire Veterans Administration Medical Center, from November 2008 through April 2014. All participants were given paper-pencil tests to diagnose MHE (98 had MHE; 48%), and 163 patients completed a standardized driving simulation. Data were collected on traffic violations and automobile accidents from the Virginia Department of Motor Vehicles and from participants' self-assessments when they entered the study, and from 73 participants 1 year later. Participants also completed a questionnaire about alcohol use and cessation patterns. The driving simulator measured crashes, run-time, road center and edge excursions, and illegal turns during navigation; before and after each driving simulation session, patients were asked to rate their overall driving skills. Drivers were classified as safe or unsafe based on crashes and violations reported on official driving records; simulation results were compared with real-life driving records. Multivariable regression analyses of real-life crashes and violations was performed using data on

Alcoholic and non-alcoholic steatohepatitis

PubMed Central

Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

2015-01-01

This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

Changes in depression mediate the effects of AA attendance on alcohol use outcomes.

PubMed

Wilcox, Claire E; Tonigan, J Scott

2018-01-01

Depression may contribute to increased drinking in individuals with alcohol use disorder. Although Alcoholics Anonymous (AA) attendance predicts drinking reductions, there is conflicting information regarding the intermediary role played by reductions in depression. We explored whether AA attendance reduces depressive symptoms, the degree to which improvement in depression results in reductions in drinking, and in which subgroups these effects occur. 253 early AA affiliates (63% male) were recruited and assessed at baseline 3, 6, 9, 12, 18, and 24 months. Depression was measured using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6, 12, 18, and 24 months. AA attendance and alcohol use outcomes were obtained with the Form 90. Mediation analyses were performed at early (3, 6, and 9 months) and late (12, 18, and 24 months) follow-up to investigate the degree to which reductions in depression mediated the effect of AA attendance on drinking, controlling for concurrent drinking. In addition, a series of moderated mediation analyses were performed using baseline depression severity as a moderator. At early follow-up, reductions in depression (6 months) mediated the effects of AA attendance (3 months) on later drinking (drinks per drinking day) (9 months) (b = -0.02, boot CI [-0.055, -0.0004]), controlling for drinking at 6 months. Baseline depression severity did not moderate the degree to which BDI mediated the effects of AA attendance on alcohol use (ps > .05). These findings provide further evidence that depression reduction is a mechanism by which AA attendance leads to reductions in alcohol use. Improving depression may help reduce alcohol use in individuals with AUD, and AA attendance may be an effective way to achieve that goal.

Social anxiety and alcohol-related impairment: The mediational impact of solitary drinking.

PubMed

Buckner, Julia D; Terlecki, Meredith A

2016-07-01

Social anxiety disorder more than quadruples the risk of developing an alcohol use disorder, yet it is inconsistently linked to drinking frequency. Inconsistent findings may be at least partially due to lack of attention to drinking context - it may be that socially anxious individuals are especially vulnerable to drinking more often in specific contexts that increase their risk for alcohol-related problems. For instance, socially anxious persons may drink more often while alone, before social situations for "liquid courage" and/or after social situations to manage negative thoughts about their performance. Among current (past-month) drinkers (N=776), social anxiety was significantly, positively related to solitary drinking frequency and was negatively related to social drinking frequency. Social anxiety was indirectly (via solitary drinking frequency) related to greater past-month drinking frequency and more drinking-related problems. Social anxiety was also indirectly (via social drinking frequency) negatively related to past-month drinking frequency and drinking-related problems. Findings suggest that socially anxious persons may be vulnerable to more frequent drinking in particular contexts (in this case alone) and that this context-specific drinking may play an important role in drinking problems among these high-risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

The influence of alcohol-specific communication on adolescent alcohol use and alcohol-related consequences.

PubMed

Reimuller, Alison; Hussong, Andrea; Ennett, Susan T

2011-12-01

Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use.

Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities?

PubMed Central

Richardson, E.A.; Hill, S.E.; Mitchell, R.; Pearce, J.; Shortt, N.K.

2015-01-01

Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18–25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment. PMID:25840352

Growth in Adolescent Delinquency and Alcohol Use in Relation to Young Adult Crime, Alcohol Use Disorders, and Risky Sex: A Comparison of Youth from Low- versus Middle-Income Backgrounds

ERIC Educational Resources Information Center

Mason, W. Alex; Hitch, Julia E.; Kosterman, Rick; McCarty, Carolyn A.; Herrenkohl, Todd I.; Hawkins, J. David

2010-01-01

Background: This study examined adolescent delinquency and alcohol use in relation to young adult crime, alcohol use disorders (AUDs), and risky sex. Analyses further examined the influences of late childhood involvement in these problem behavior outcomes, with mediation through teen delinquency and alcohol use, and examined differences in the…

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

PubMed

Bucci, L; Garuti, F; Camelli, V; Lenzi, B; Farinati, F; Giannini, E G; Ciccarese, F; Piscaglia, F; Rapaccini, G L; Di Marco, M; Caturelli, E; Zoli, M; Borzio, F; Sacco, R; Maida, M; Felder, M; Morisco, F; Gasbarrini, A; Gemini, S; Foschi, F G; Missale, G; Masotto, A; Affronti, A; Bernardi, M; Trevisani, F

2016-02-01

Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients. © 2015 John Wiley & Sons Ltd.

Alcohol and the heart: to abstain or not to abstain?

PubMed

Movva, Rajesh; Figueredo, Vincent M

2013-04-15

Alcohol has been consumed by most societies over the last 7000 years. Abraham Lincoln said "It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing." Light to moderate alcohol consumption reduces the incidence of coronary heart disease (CHD), ischemic stroke, peripheral arterial disease, CHD mortality, and all-cause mortality, especially in the western populations. However, heavy alcohol consumption is detrimental causing cardiomyopathy, cardiac arrhythmias, hepatic cirrhosis, pancreatitis, and hemorrhagic stroke. In this article, we review the effects of alcohol on CHD, individual cardiovascular risk factors, cardiomyopathy, and cardiac arrhythmias, including the most recent evidence of the effects of alcohol on CHD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Is local alcohol outlet density related to alcohol-related morbidity and mortality in Scottish cities?

PubMed

Richardson, E A; Hill, S E; Mitchell, R; Pearce, J; Shortt, N K

2015-05-01

Alcohol consumption may be influenced by the local alcohol retailing environment. This study is the first to examine neighbourhood alcohol outlet availability (on- and off-sales outlets) and alcohol-related health outcomes in Scotland. Alcohol-related hospitalisations and deaths were significantly higher in neighbourhoods with higher outlet densities, and off-sales outlets were more important than on-sales outlets. The relationships held for most age groups, including those under the legal minimum drinking age, although were not significant for the youngest legal drinkers (18-25 years). Alcohol-related deaths and hospitalisations were higher in more income-deprived neighbourhoods, and the gradient in deaths (but not hospitalisations) was marginally larger in neighbourhoods with higher off-sales outlet densities. Efforts to reduce alcohol-related harm should consider the potentially important role of the alcohol retail environment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cirrhosis - discharge

MedlinePlus

Liver failure - discharge; Liver cirrhosis - discharge ... You have cirrhosis of the liver. Scar tissue forms and your liver gets smaller and harder. Most of the time, this damage cannot be undone. However, the ...

The Influence of Alcohol-specific Communication on Adolescent Alcohol Use and Alcohol-related Consequences

PubMed Central

Reimuller, Alison; Hussong, Andrea; Ennett, Susan T.

2013-01-01

Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use. PMID:21667141

On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

PubMed

Etelälahti, T J; Eriksson, C J P

2013-11-01

Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction. © 2013.

Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.

PubMed

Dasarathy, Jaividhya; McCullough, Arthur J; Dasarathy, Srinivasan

2017-08-01

Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in

Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.

PubMed

Albillos, Agustín; Hera Ad, Antonio de la; Reyes, Eduardo; Monserrat, Jorge; Muñoz, Leticia; Nieto, Mónica; Prieto, Alfredo; Sanz, Eva; Alvarez-Mon, Melchor

2004-04-01

To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis. Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo. Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis. In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.

Survival and risk factors related to death in outpatients with cirrhosis treated in a clinic in Southern Brazil.

PubMed

John, Jorge Alberto; de Mattos, Angelo Alves; da Silva Miozzo, Suelen Aparecida; Comerlato, Pedro Henrique; Porto, Mariana; Contiero, Priscila; da Silva, Renata Rodrigues

2015-12-01

Cirrhosis represents a public health issue that generally evolves and presents serious complications. To assess the outcomes of outpatients with cirrhosis. We used a retrospective outpatient-based cohort, assessing 527 patients with cirrhosis. Demographic, clinical, and laboratory variables were analyzed, as well as the risk factors related to death, using the Cox proportional-hazard regression model. The Kaplan-Meier method was used to analyze survival rates. Patients had a mean age of 52.9±9.7 years and were more frequently men (59%), presenting Child-Turcotte-Pugh B or C in 43% of the cases in addition to a mean Model for End-Stage Liver Disease score of 12.0±4.1. The predominant etiology of liver disease was the hepatitis C virus. The most frequent complications during follow-up were ascites (34%), hepatic encephalopathy (17%), and hepatocellular carcinoma (17%). The survival rate at years 5 and 10 was 73 and 57%, respectively. The main risk factors that were related to death were, in a multivariate analysis, hepatitis C virus etiology, presence of hepatocellular carcinoma, and serum levels of albumin. Patients with cirrhosis monitored on an outpatient basis, despite showing a reasonable survival rate, have a worse prognosis when the etiology of liver disease is related to hepatitis C virus and when they have hepatocellular carcinoma or hypoalbuminemia.

Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores

PubMed Central

Oltmanns, Annett; Güttler, Andrea; Petroff, David; Wirtz, Hubert; Mainz, Jochen G.; Mössner, Joachim; Berg, Thomas; Tröltzsch, Michael; Keim, Volker; Wiegand, Johannes

2012-01-01

Background Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. Aim We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. Methods TE and ARFI were performed in 55 adult CF patients. In addition, AST/Platelets-Ratio-Index (APRI), and Forns' score were calculated. Healthy probands and patients with alcoholic liver cirrhosis served as controls. Results Fourteen CF patients met CFLD criteria, six had liver cirrhosis. Elastography acquisition was successful in >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar to CF patients without liver involvement. Cases with liver cirrhosis differed significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE: 7.95 vs. 4.16 kPa; p = 0.020) and had significantly lower results than individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002). APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815; sensitivity 85.7%, specificity 70.7%). Conclusions ARFI, TE, and laboratory based fibrosis indices correlate with each other and reliably detect CFLD related liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in adults are lower than in alcoholic cirrhosis. PMID:22848732

Human alcohol-related neuropathology

PubMed Central

Kril, Jillian J.

2015-01-01

Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

Multiple pathogenic factor-induced complications of cirrhosis in rats: A new model of hepatopulmonary syndrome with intestinal endotoxemia

PubMed Central

Zhang, Hui-Ying; Han, De-Wu; Zhao, Zhong-Fu; Liu, Ming-She; Wu, Yan-Jun; Chen, Xian-Ming; Ji, Cheng

2007-01-01

AIM: To develop and characterize a practical model of Hepatopulmonary syndrome (HPS) in rats. METHODS: The experimental animals were randomized into five feeding groups: (1) control (fed standard diet), (2) control plus intraperitoneal injection with lipopolysaccharide (LPS), (3) cirrhosis (fed a diet of maize flour, lard, cholesterol, and alcohol plus subcutaneously injection with carbon tetrachloride (CCl4) oil solution), (4) cirrhosis plus LPS, and (5) cirrhosis plus glycine and LPS. The blood, liver and lung tissues of rats were sampled for analysis and characterization. Technetium 99m-labeled macroaggregated albumin (Tc99m-MAA) was used to test the dilatation of pulmonary microvasculature. RESULTS: Typical cirrhosis and subsequent hepato-pulmonary syndrome was observed in the cirrhosis groups after an 8 wk feeding period. In rats with cirrhosis, there were a decreased PaO2 and PaCO2 in arterial blood, markedly decreased arterial O2 content, a significantly increased alveolar to arterial oxygen gradient, an increased number of bacterial translocated within mesenteric lymph node, a significant higher level of LPS and tumor necrosis factor-α (TNF-α) in plasma, and a significant greater ratio of Tc99m-MAA brain-over-lung radioactivity. After LPS administration in rats with cirrhosis, various pathological parameters got worse and pulmonary edema formed. The predisposition of glycine antagonized the effects of LPS and significantly alleviated various pathological alterations. CONCLUSION: The results suggest that: (1) a characte-ristic rat model of HPS can be non-invasively induced by multiple pathogenic factors including high fat diet, alcohol, cholesterol and CCl4; (2) this model can be used for study of hepatopulmonary syndrome and is clinically relevant; and (3) intestinal endotoxemia (IETM) and its accompanying cytokines, such as TNF-α, exert a crucial role in the pathogenesis of HPS in this model. PMID:17659698

Alcohol on campus: alcohol-related emergencies in undergraduate college students.

PubMed

Wright, S W; Norton, V C; Dake, A D; Pinkston, J R; Slovis, C M

1998-10-01

We reviewed demographic factors associated with alcohol-related disorders in undergraduates seen in the emergency department (ED) and determined the incidence of alcohol-related ED visits among undergraduates. This prospective, observational study was done in a university-affiliated emergency department. Demographic variables and incidence of students with alcohol-related disorders were analyzed. Of the 616 students seen in the ED during 1 academic year, 101 (16%) had an alcohol-related disorder. White students and freshmen were overrepresented. There were equal numbers of male and female students. The overall annual incidence for an alcohol-related visit among undergraduates was 1.7% per academic year. The incidence for freshmen was 2.9%. Four students were admitted; one died of a severe head injury. We estimate that 1 of every 15 undergraduates at our college comes to our ED with an alcohol-related problem during their 4-year college career. Younger and nonminority students were more commonly seen; there was no difference by sex. Serious outcomes included one death. This study probably underestimates the true incidence of alcohol-related disorders among students on campus.

Subcirrhotic liver stiffness by FibroScan correlates with lower risk of hepatocellular carcinoma in patients with HBV-related cirrhosis.

PubMed

Jeon, Mi Young; Lee, Hye Won; Kim, Seung Up; Heo, Ja Yoon; Han, Sojung; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub

2017-05-01

The risk of developing hepatocellular carcinoma (HCC) varies, even in the context of cirrhosis. We investigated the relationship between liver stiffness (LS) in subcirrhotic range, assessed via transient elastography (TE), and risk of HCC development in patients with chronic hepatitis B (CHB)-related cirrhosis. Data on 540 patients presenting with clinically evident CHB-related cirrhosis between April 2006 and December 2014 were reviewed retrospectively. Subcirrhotic range of LS was defined by TE values ≤13 kPa. Of the study population, 214 (39.6%) had LS values in the subcirrhotic range. During follow-up (median 54.1 months), 81 patients (15.0%) developed HCC. In conjunction with age, male gender, and diabetes mellitus, subcirrhotic LS value (hazard ratio = 0.462) was an independent predictor of HCC development on multivariate analysis (all p < 0.05). Cumulative HCC incidence was significantly lower for patients in subcirrhotic (versus cirrhotic) LS range (log-rank test, p < 0.05). In our cohort, the modified REACH-B score performed better than other prediction models, namely REACH-B, CU-HCC, and LSM-HCC scoring systems (area under receiver operating characteristic curve: 0.717 versus 0.669, 0.578, and 0.624, respectively, for 7-year HCC risk). A significant association between subcirrhotic range of LS value and lower risk of HCC development was identified in patients with clinically evident CHB-related cirrhosis. Thus, different TE-based HCC surveillance strategies may be required even in patients with identical liver cirrhosis disease category.

Vitamin D deficiency is a risk factor for infections in patients affected by HCV-related liver cirrhosis.

PubMed

Buonomo, Antonio Riccardo; Zappulo, Emanuela; Scotto, Riccardo; Pinchera, Biagio; Perruolo, Giuseppe; Formisano, Pietro; Borgia, Guglielmo; Gentile, Ivan

2017-10-01

To evaluate the prevalence of vitamin D deficiency and its impact on infections in HCV-related liver cirrhosis. We enrolled 291 patients affected by HCV-related liver cirrhosis. Serum vitamin D levels were dosed at enrolment. The presence of infection was assessed at baseline and during follow-up based on physical examination and laboratory analyses. Vitamin D deficiency (<20ng/mL) was diagnosed in 68.3% of patients, and a total of 102 infections were detected. Urinary tract infections were the most common infections diagnosed (41.2%). Vitamin D deficiency rates were higher in patients with decompensated cirrhosis (Child-Pugh B vs A p=0.008, and Child-Pugh C vs A p=0.024). Infection was significantly associated with vitamin D deficiency (p<0.001), MELD score >15 (p=0.003), Child-Pugh class B/C vs A (p<0.001), and active hepatocellular carcinoma (HCC) (p<0.001). At multivariate analysis, vitamin D deficiency (p<0.01), HCC (p<0.05), hospitalization (p<0.001) and exposure to immunosuppressant agents (p<0.05) were independent risk factors for infection at baseline. Vitamin D may play a role in the development of infections in patients affected by liver cirrhosis, and preventive strategies with vitamin D supplementation are to be evaluated in randomized controlled trials. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Intermediate hepatobiliary cells predict an increased risk of hepatocarcinogenesis in patients with hepatitis C virus-related cirrhosis.

PubMed

Ziol, Marianne; Nault, Jean-Charles; Aout, Mounir; Barget, Nathalie; Tepper, Maryline; Martin, Antoine; Trinchet, Jean-Claude; Ganne-Carrié, Nathalie; Vicaut, Eric; Beaugrand, Michel; N'Kontchou, Gisele

2010-07-01

The expression of biliary lineage markers such as cytokeratin (K) 7 by hepatocytes is thought to reflect an altered regeneration pathway recruiting a stem cell compartment, more prone to carcinogenesis. We aimed to investigate the presence of these so-called intermediate hepatobiliary cells (IHC) in liver biopsies of patients with hepatitis C-related cirrhosis and their potential influence on the subsequent occurrence of hepatocellular carcinoma (HCC). From a cohort of patients with hepatitis C-related cirrhosis, prospectively screened for HCC, we retrospectively selected those with a liver biopsy performed for the initial diagnosis of cirrhosis. Presence of IHC was recorded when foci of K7-positive, intermediate-sized hepatocytes were detected. A total of 150 patients were included (87 men; mean age, 57 y; range, 19-84 y; body mass index, 25 kg/m(2)). After a median follow-up period of 4.85 years, HCC was diagnosed in 36 patients (24%). Baseline liver biopsy showed intermediate hepatobiliary cell foci in 61 patients (41%). Intermediate cells co-expressed both hepatocytes markers and the progenitor cell markers Ep-CAM and K19. The presence of intermediate hepatobiliary cells was associated independently with HCC occurrence (Fine and Gray model; hazard ratio, 2.48; 95% confidence interval, 1.24-4.96; P = .01). Other predictors of HCC were diabetes and low platelet count. The HCC annual incidence rate was significantly higher in patients with IHC compared with patients without (8.14% vs 3.12%, Gray's test, P = .003). The aberrant expression of biliary K by hepatocytes in patients with hepatitis C virus-related cirrhosis is related independently to HCC occurrence. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Meta-Analysis of the Association of Alcohol-Related Social Media Use with Alcohol Consumption and Alcohol-Related Problems in Adolescents and Young Adults.

PubMed

Curtis, Brenda L; Lookatch, Samantha J; Ramo, Danielle E; McKay, James R; Feinn, Richard S; Kranzler, Henry R

2018-06-01

Despite the pervasive use of social media by young adults, there is comparatively little known about whether, and how, engagement in social media influences this group's drinking patterns and risk of alcohol-related problems. We examined the relations between young adults' alcohol-related social media engagement (defined as the posting, liking, commenting, and viewing of alcohol-related social media content) and their drinking behavior and problems. We conducted a systematic review and meta-analysis of studies evaluating the association of alcohol consumption and alcohol-related problems with alcohol-related social media engagement. Summary baseline variables regarding the social media platform used (e.g., Facebook and Twitter), social media measures assessed (e.g., number of alcohol photographs posted), alcohol measures (e.g., Alcohol Use Disorders Identification Test and Timeline Follow back Interview), and the number of time points at which data were collected were extracted from each published study. We used the Q statistic to examine heterogeneity in the correlations between alcohol-related social media engagement and both drinking behavior and alcohol-related problems. Because there was significant heterogeneity, we used a random-effects model to evaluate the difference from zero of the weighted aggregate correlations. We used metaregression with study characteristics as moderators to test for moderators of the observed heterogeneity. Following screening, 19 articles met inclusion criteria for the meta-analysis. The primary findings indicated a statistically significant relationship and moderate effect sizes between alcohol-related social media engagement and both alcohol consumption (r = 0.36, 95% CI: 0.29 to 0.44, p < 0.001) and alcohol-related problems (r = 0.37, 95% CI: 0.21 to 0.51, p < 0.001). There was significant heterogeneity among studies. Two significant predictors of heterogeneity were (i) whether there was joint measurement of alcohol-related

Temporal Trends of Non-alcoholic Fatty Liver Disease-related Hepatocellular Carcinoma in the Veteran Affairs Population

PubMed Central

Mittal, Sahil; Sada, Yvonne H.; El-Serag, Hashem B.; Kanwal, Fasiha; Duan, Zhigang; Temple, Sarah; May, Sarah B.; Kramer, Jennifer R.; Richardson, Peter A.; Davila, Jessica A.

2014-01-01

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. Methods We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients’ full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, HCV), as well HCC surveillance and outcomes, among HCC patients. Results NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%–12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%–68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%–80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%–3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared to patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P<.05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared to patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than of patients with HCV-related HCC (77.5%; P<.01). However, 1-year survival did not differ among patients with HCC related to different risk factors

Association of HFE gene C282Y and H63D mutations with liver cirrhosis in the Lithuanian population.

PubMed

Juzėnas, Simonas; Kupčinskas, Juozas; Valantienė, Irena; Šumskienė, Jolanta; Petrenkienė, Vitalija; Kondrackienė, Jūrate; Kučinskas, Laimutis; Kiudelis, Gediminas; Skiecevičienė, Jurgita; Kupčinskas, Limas

2016-01-01

Liver cirrhosis is the end-stage disease of chronic liver injury. Due to differences in the natural course of chronic liver diseases, identification of genetic factors that influence individual outcomes is warranted. HFE-linked hereditary hemochromatosis (HH) predisposes disease progression to cirrhosis; however, the role of heterozygous C282Y or H63D mutations in the development of cirrhosis in the presence of other etiological factors is still debated. The aim of this study was to determine the association between heterozygous C282Y and H63D mutations and non-HH liver cirrhosis in Lithuanian population. The patient cohort consisted of 209 individuals. Diagnosis of cirrhosis was confirmed by clinical, laboratory parameters, liver biopsy, and radiological imaging. Control samples were obtained from 1005 randomly selected unrelated healthy individuals. HFE gene mutations were determined using the PCR-RFLP method. The most common causes of cirrhosis were hepatitis C (33.9%), hepatitis B (13.6%), and alcohol (25.8%). C282Y allele was associated with the presence of cirrhosis (OR=2.07; P=0.005); this was also observed under recessive model for C282Y (OR=2.06, P=0.008). The prevalence of C282Y allele was higher in cirrhotic men than in controls (7.0% vs. 2.8%, P=0.002). The carriage of H63D risk allele (OR=1.54; P=0.02), heterozygous C282Y/wt and homozygous H63D/H63D genotypes were associated with liver cirrhosis in males (OR=2.48, P=0.008, and OR=4.13, P=0.005, respectively). Heterozygous C282Y mutation of the HFE gene was associated with liver cirrhosis in the Lithuanian population. In gender-related analysis, heterozygous C282Y and homozygous H63D mutations were linked to liver cirrhosis in men, not in women. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Mediation of Family Alcoholism Risk by Religious Affiliation Types*

PubMed Central

Haber, Jon Randolph; Jacob, Theodore

2009-01-01

Objective: Religious affiliation is inversely associated with alcohol dependence (AD). Our previous findings indicated that when a religious affiliation differentiated itself from cultural norms, then high-risk adolescents (those having parents with alcoholism history) raised with these affiliations exhibited fewer AD symptoms compared with adolescents of other religious affiliations and nonreligious adolescents. The first of two studies reported here provides a needed replication of our previous findings for childhood religious affiliation using a different sample, and the second study extends examination to current religious affiliation. Method: A national sample of male and female adolescents/young adults (N = 1,329; mean age = 19.6 years) was selected who were the offspring of members of the Vietnam Era Twin Registry. Parental alcoholism, religious affiliation types, and their interactions were examined as predictors of offspring AD symptoms. Results: (1) Offspring reared with a differentiating religious affiliation during childhood exhibited significantly fewer AD symptoms as young adults; (2) offspring with current differentiating religious affiliation also exhibited fewer AD symptoms; this main effect was not weakened by adding other measures of religiousness to the model; (3) differentiating religious affiliation was correlated with both family alcoholism risk and offspring outcome, and removed the association between family alcoholism risk and offspring outcome, thus indicating that differentiating religious affiliation was at least a partial mediator of the association between family AD history risk and offspring AD outcome. Conclusions: Current results indicate that religious differentiation is an inverse mediator of alcoholism risk for offspring with or without parental AD history and regardless of the influence of other religion variables. Results replicated our previous report on religious upbringing between ages 6 and 13 years and indicated an even

Role of Oxygen Free Radicals, Nitric Oxide and Mitochondria in Mediating Cardiac Alterations During Liver Cirrhosis Induced by Thioacetamide.

PubMed

Amirtharaj, G Jayakumar; Natarajan, Sathish Kumar; Pulimood, Anna; Balasubramanian, K A; Venkatraman, Aparna; Ramachandran, Anup

2017-04-01

Thioacetamide (TAA) administration is widely used for induction of liver cirrhosis in rats, where reactive oxygen radicals (ROS) and nitric oxide (NO) participate in development of liver damage. Cardiac dysfunction is an important complication of liver cirrhosis, but the role of ROS or NO in cardiac abnormalities during liver cirrhosis is not well understood. This was investigated in animals after TAA-induced liver cirrhosis and temporal changes in oxidative stress, NO and mitochondrial function in the heart evaluated. TAA induced elevation in cardiac levels of nitrate before development of frank liver cirrhosis, without gross histological alterations. This was accompanied by an early induction of P38 MAP kinase, which is influenced by ROS and plays an important signaling role for induction of iNOS. Increased nitrotyrosine, protein oxidation and lipid peroxidation in the heart and cardiac mitochondria, suggestive of oxidative stress, also preceded frank liver cirrhosis. However, compromised cardiac mitochondrial function with a decrease in respiratory control ratio and increased mitochondrial swelling was seen later, when cirrhosis was evident. In conclusion, TAA induces elevations in ROS and NO in the heart in parallel to early liver damage. This leads to later development of functional deficits in cardiac mitochondria after development of liver cirrhosis.

Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease

PubMed Central

Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina

2015-01-01

Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770

Alcoholism: a systemic proinflammatory condition.

PubMed

González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

2014-10-28

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

Difficulties in emotion regulation mediate negative and positive affects and craving in alcoholic patients.

PubMed

Khosravani, Vahid; Sharifi Bastan, Farangis; Ghorbani, Fatemeh; Kamali, Zoleikha

2017-08-01

The aim of this study was to assess the mediating effects of difficulties in emotion regulation (DER) on the relations of negative and positive affects to craving in alcoholic patients. 205 treatment-seeking alcoholic outpatients were included. DER, positive and negative affects as well as craving were evaluated by the Difficulties in Emotion Regulation Scale (DERS), the Positive/Negative Affect Scales, and the Obsessive Compulsive Drinking Scale (OCDS) respectively. Clinical factors including depression and severity of alcohol dependence were investigated by the Alcohol Use Disorders Identification Test (AUDIT) and the Beck Depression Inventory-II (BDI-II) respectively. Results revealed that both increased negative affect and decreased positive affect indirectly influenced craving through limited access to emotion regulation strategies. It was concluded that limited access to emotion regulation strategies may be important in predicting craving for alcoholics who experience both increased negative affect and decreased positive affect. This suggests that treatment and prevention efforts focused on increasing positive affect, decreasing negative affect and teaching effective regulation strategies may be critical in reducing craving in alcoholic patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal Associations from Neurobehavioral Disinhibition to Adolescent Risky Sexual Behavior in Boys: Direct and Mediated Effects through Moderate Alcohol Consumption

PubMed Central

Riggs, Nathaniel R.; Tate, Eleanor B.; Ridenour, Ty A.; Reynolds, Maureen D.; Zhai, Zu W.; Vanyukov, Michael M.; Tarter, Ralph E.

2013-01-01

Purpose This longitudinal study tested the hypothesis that neurobehavioral disinhibition (ND) in childhood, mediated by alcohol use, portends risky sexual behavior (number of sexual partners) in mid-adolescence. Methods Participants were 410 adolescent boys. Neurobehavioral disinhibition was assessed at 11.3 years of age. Frequency and quantity of alcohol use on a typical drinking occasion were assessed at 13.4 years of age at first follow-up and sexual behavior at 16.0 years at second follow-up. Results Quantity of alcohol consumed on a typical drinking occasion, but not frequency of alcohol use, mediated the relation between ND and number of sexual partners. Conclusions These findings indicate that number of sexual partners in mid-adolescence is predicted by individual differences in boys’ psychological self-regulation during childhood and moderate alcohol consumption in early adolescence, and that ND may be a potential target for multi-outcome public health interventions. PMID:23876782

Alcohol-Related Problems and Risk of Suicide among College Students: The Mediating Roles of Belongingness and Burdensomeness

ERIC Educational Resources Information Center

Lamis, Dorian A.; Malone, Patrick S.

2011-01-01

The relationship among alcohol-related problems, perceived burdensomeness, thwarted belongingness, and suicide proneness in undergraduate college students (N = 996) was examined. As hypothesized, alcohol-related problems, perceived burdensomeness, and thwarted belongingness were all significantly and positively correlated with suicide proneness.…

Interactive and Indirect Effects of Anxiety and Negative Urgency on Alcohol-Related Problems

PubMed Central

Menary, Kyle R.; Corbin, William R.; Leeman, Robert F.; Fucito, Lisa M.; Toll, Benjamin A.; DeMartini, Kelly; O’Malley, Stephanie S.

2015-01-01

Background Although drinking for tension reduction has long been posited as a risk factor for alcohol-related problems, studies investigating anxiety in relation to risk for alcohol problems have returned inconsistent results, leading researchers to search for potential moderators. Negative urgency (the tendency to become behaviorally dysregulated when experiencing negative affect) is a potential moderator of theoretical interest because it may increase risk for alcohol problems among those high in negative affect. The present study tested a cross-sectional mediated moderation hypothesis whereby an interactive effect of anxiety and negative urgency on alcohol problems is mediated through coping-related drinking motives. Method The study utilized baseline data from a hazardously drinking sample of young adults (N = 193) evaluated for participation in a randomized controlled trial of naltrexone and motivational interviewing for drinking reduction. Results The direct effect of anxiety on physiological dependence symptoms was moderated by negative urgency such that the positive association between anxiety and physiological dependence symptoms became stronger as negative urgency increased. Indirect effects of anxiety and negative urgency on alcohol problems (operating through coping motives) were also observed. Conclusions Although results of the current cross-sectional study require replication using longitudinal data, the findings suggest that the simultaneous presence of anxiety and negative urgency may be an important indicator of risk for AUDs via both direct interactive effects and indirect additive effects operating through coping motives. These findings have potentially important implications for prevention/intervention efforts for individuals who become disinhibited in the context of negative emotional states. PMID:26031346

Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?

PubMed

Lotti, Marcello

2017-05-01

Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure-response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta-analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross-sectional study. However, a meta-analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Non alcoholic steatohepatitis].

PubMed

Manero, E; Findor, J A; Avagnina, A; de Elizalde, S; Elsner, B

1994-01-01

A prospective study of 21 patients with the diagnosis of non-alcoholic steatohepatitis (NASH) was carried out. All patients had hepatomegaly and in 10 (48%) image studies were consistent with steatosis and/or fibrosis. Biochemically, there was increase of AST, ALT and cholesterol in 48%, of GGT in 52% and of alkaline phosphatase in 38%. 18 patients were obese, 2 of them diabetic, 2 others had a history of exposure to drugs (amiodarone and isopropilic alcohol) and the last one presented hypothyroidism. Liver biopsies were studied using a semiquantitative scale to evaluate the degree of steatosis, inflammation and fibrosis in a scale from 1 to 3. Results showed a medium score of 2.6 for steatosis, 1.5 for inflammation and 1.8 for fibrosis. Four patients had cirrhosis and Mallory bodies were found in 11 cases (52%). NASH is an oligosymptomatic disease that can be found in different clinical conditions, mainly obesity, and is more frequent in women. It is histologically indistinguishable from alcoholic steatohepatitis. It is frequently underdiagnosed clinically and must be taken into account as a possible cause of cryptogenetic cirrhosis.

Do community characteristics predict alcohol-related crime?

PubMed

Breen, Courtney; Shakeshaft, Anthony; Slade, Tim; Love, Stephanie; D'Este, Catherine; Mattick, Richard P

2011-01-01

Alcohol-related crime is a substantial community problem. There is evidence to suggest that certain geographic areas experience higher rates of alcohol-related crime and that both individual and community factors are associated with alcohol-related crime. There is limited research at the community level despite communities being the target of interventions designed to reduce alcohol-related harm. This study aims to determine whether there are differences in alcohol-related crime at the community level and examines whether certain community characteristics are associated with increased alcohol-related crime. Routinely collected police data from 20 rural communities in New South Wales, Australia were analysed. The ratio of alcohol to non-alcohol-related criminal incidents was used as a proxy for alcohol-related crime. Predictor variables were population-adjusted community characteristics, including demographic and resource variables. Regression analyses suggest that there are differences between communities in alcohol-related crime. Less socioeconomic disadvantage and more GPs and licensed premises (pubs and clubs) are associated with greater alcohol-related crime at the community level. Decreasing the socioeconomic well-being of a community is not appropriate; however, introducing additional taxes to increase the cost of alcohol may decrease consumption and therefore alcohol-related crime. Reducing or capping the number of licensed premises, specifically the number of pubs and clubs, may be an appropriate strategy to reduce alcohol-related crime in rural communities.

Childhood maltreatment severity and alcohol use in adult psychiatric inpatients: The mediating role of emotion regulation difficulties.

PubMed

Dutcher, Christina D; Vujanovic, Anka A; Paulus, Daniel J; Bartlett, Brooke A

2017-09-01

Emotion regulation difficulties are a potentially key mechanism underlying the association between childhood maltreatment and alcohol use in adulthood. The current study examined the mediating role of emotion regulation difficulties in the association between childhood maltreatment severity (i.e., Childhood Trauma Questionnaire total score) and past-month alcohol use severity, including alcohol consumption frequency and alcohol-related problems (i.e., number of days of alcohol problems, ratings of "bother" caused by alcohol problems, ratings of treatment importance for alcohol problems). Participants included 111 acute-care psychiatric inpatients (45.0% female; Mage=33.5, SD=10.6), who reported at least one DSM-5 posttraumatic stress disorder Criterion A traumatic event, indexed via the Life Events Checklist for DSM-5. Participants completed questionnaires regarding childhood maltreatment, emotion regulation difficulties, and alcohol use. A significant indirect effect of childhood maltreatment severity via emotion regulation difficulties in relation to alcohol use severity (β=0.07, SE=0.04, 99% CI [0.01, 0.21]) was documented. Specifically, significant indirect effects were found for childhood maltreatment severity via emotion regulation difficulties in relation to alcohol problems (β's between 0.05 and 0.12; all 99% bootstrapped CIs with 10,000 resamples did not include 0) but not alcohol consumption. Emotion regulation difficulties may play a significant role in the association between childhood maltreatment severity and alcohol outcomes. Clinical implications are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-communicable diseases at a regional hospital in Nepal: Findings of a high burden of alcohol-related disease.

PubMed

Amundsen, M S; Kirkeby, T M G; Giri, S; Koju, R; Krishna, S S; Ystgaard, B; Solligård, E; Risnes, K

2016-12-01

Recent global burden of disease reports find that a major proportion of global deaths and disability worldwide can be attributed to alcohol use. Thus, it may be surprising that very few studies have reported on the burden of alcohol-related disease in low income settings. The evidence of non-communicable disease (NCD) burden in Nepal was recently reviewed and concluded that data is still lacking, particularly to describe the burden of alcohol-related diseases (ARDs). Therefore, here we report on NCD burden and specifically ARDs, in hospitalized patients at a regional hospital in Nepal. We conducted a retrospective chart-review that included detailed information on all discharged patients during a four month period. A local database that included sociodemographic information and diagnoses at discharge was established. All doctor-assigned discharge diagnoses were retrospectively assigned ICD-10 codes. A total of 1,139 hospitalized adult patients were included in the study and one third of these were NCDs (n = 332). The main NCDs were chronic obstructive pulmonary disease (COPD) (n = 148, 45%) and ARDs (n = 57, 17%). Patients with ARD often presented with signs of liver cirrhosis and were typically younger men, with a median age at 43 years, from specific ethnic groups. These data demonstrate that severe alcohol-related organ failure in relatively young men contributed to a high proportion of NCDs in a regional hospital in Nepal. These findings are novel and alarming and warrant further studies that can establish the burden of ARDs and alcohol use in Nepal and other similar low-income countries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Alcohol use, alcohol-related aggression and intimate partner abuse: A cross-sectional survey of convicted versus general population men in Scotland.

PubMed

Gilchrist, Elizabeth Allison; Ireland, Lana; Forsyth, Alasdair; Godwin, Jon; Laxton, Tim

2017-01-01

Scotland has a particular problem with alcohol, and the links between intimate partner abuse (IPA) and alcohol appear stronger here than elsewhere across Europe. This study explored differences in alcohol use, related aggression and relationship conflict across a number of groups: men convicted for intimate partner abuse, men convicted of general offences and men recruited from community sports teams. Participants (n = 64) completed three questionnaires exploring their experiences of alcohol use (Alcohol Use Disorders Identification Test, AUDIT); alcohol and aggression (Alcohol Related Aggression Questionnaire, ARAQ-28), and relationship conflict (Revised Conflict Tactics Scale, CTS-2). There were significant differences across the groups in terms of AUDIT and ARAQ-28 scores, IPA and general offenders scored higher than the community sample. CTS-2 scores showed significant differences: both offender groups reported more use of negotiation and psychological abuse, than the community men, and IPA offenders reported causing more physical harm than either general offenders or the community sample. ARAQ-28 scores correlated with psychological abuse for general offenders. Alcohol use was very high across all groups, but the community group did not endorse an aggression-precipitating view of alcohol and did not report high IPA. Discussed is the need for cross-cultural research to explore putative mediators and moderators in the relationship between alcohol, aggressiveness and IPA. [Gilchrist EA, Ireland L, Forsyth A, Godwin J, Laxton T. Alcohol use, alcohol-related aggression and intimate partner abuse: A cross-sectional survey of convicted versus general population men in Scotland. Drug Alcohol Rev 2017;36:20-23]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Emotion dysregulation and peer drinking norms uniquely predict alcohol-related problems via motives.

PubMed

Simons, Raluca M; Hahn, Austin M; Simons, Jeffrey S; Murase, Hanako

2017-08-01

This study examined the relationships between emotion dysregulation, peer drinking norms, drinking motives, and alcohol-related outcomes among 435 college students. We examined the mediating roles of drinking motives when predicting alcohol consumption and related problems from the subscales of the Difficulties in Emotion Regulation Scale (DERS; Gratz and Roemer, 2004) via negative and positive reinforcement models. First, we hypothesized that individuals who lack in emotion regulation strategies or have difficulties in accepting negative emotions are more likely to drink to cope. Additionally, we hypothesized that individuals who act impulsively or become distracted when upset as well as those with higher peer drinking norms are more likely to drink for social and enhancement motives. The results of the path model indicated that limited access to emotion regulation strategies significantly predicted alcohol-related problems via both depression and anxiety coping motives, but did not predict alcohol consumption. Nonacceptance of emotional responses was not significantly associated with coping motives. Impulsivity had a significant direct relationship with alcohol problems. Difficulty in engaging in goal-directed behaviors predicted both enhancement and social motives, but only enhancement motives in turn predicted consumption. Norms indirectly predicted problems via enhancement motives and consumption. The results indicated that using alcohol to reduce negative or to increase positive emotions increases alcohol consumption and alcohol-related problems. Overall, results advance our understanding of the mechanisms of increased alcohol use and problems among college students. Copyright © 2017 Elsevier B.V. All rights reserved.

Parental Mediation in the Digital Era: Increasing Children's Critical Thinking May Help Decrease Positive Attitudes toward Alcohol.

PubMed

Radanielina Hita, Marie Louise; Kareklas, Ioannis; Pinkleton, Bruce

2018-01-01

We demonstrate in our research that discussion-based parental mediation may successfully decrease the negative effects that youth's engagement with alcohol brands on social media may have on attitudes toward alcohol through its effects on critical thinking. A clear pattern was found with positive mediation leading to unhealthy outcomes and negative mediation predicting healthier behaviors. Youth whose parents critiqued media messages reported more critical thinking skills, which predicted less interaction with alcohol brands on social media and fewer expectancies toward alcohol. On the other hand, youth whose parents endorsed media portrayals of drinking reported fewer critical thinking skills and were thus more likely to interact with alcohol brands on social media. Including a media literacy component in alcohol education that target parental strategies and that are conducive to discussion may lead to beneficial health outcomes in the digital era.

[Severe anemia caused by haemorrhoids: the casae of a young man with toxic cirrhosis].

PubMed

Kovács, Erzsébet; Palatka, Károly; Németh, Attila; Pásztor, Éva; Pfliegler, György

2013-03-10

A 38-year-old alcoholic man with severe iron deficient anaemia, and bloody-mucous stool was found to have haemorrhoidal bleeding. In spite of intravenous iron supplements haemoglobin levels were falling. He was admitted because of deteriorating condition, jaundice, severe anaemia (haemoglobin, 38 g/l) and iron deficiency. Except of toxic (alcohol) agent all other causes of liver disease could be excluded. Sclero-, and medical therapy, and abstinence resulted in a rapid improvement in his condition and subsequently rectal bleeding also disappeared. Bleeding from the upper gastrointestinal tract is a well known and serious complication in liver cirrhosis, however, a voluminous blood loss resulting in a life-threatening anaemia from lower gastrointestinal tract or haemorrhoids, as it was detected in this patient, is quite rare. Sclerotherapy seems to be an effective method with only minor complications when compared with other invasive techniques. However, the patient's compliance even in liver cirrhosis with haemorrhoidal nodes is essential for long-term success.

Transient elastography using Fibroscan is the most reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in alcoholic liver disease.

PubMed

Fernandez, Michael; Trépo, Eric; Degré, Delphine; Gustot, Thierry; Verset, Laurine; Demetter, Pieter; Devière, Jacques; Adler, Michael; Moreno, Christophe

2015-09-01

Fibroscan (FS) is a reliable noninvasive method for the diagnosis of advanced fibrosis and cirrhosis in chronic liver disease. However, there is no clear consensus with respect to the best FS cut-off values for use in alcoholic liver disease (ALD). The aims of this study were as follows: (a) to compare the performance of FS and different biochemical markers in ALD patients; (b) to assess the best FS cut-off values for the prediction of fibrosis stage in our ALD population; and (c) to assess the influence of aspartate aminotransferase (AST) values on FS. This retrospective study included 135 consecutive and compensated ALD patients who underwent liver biopsy between November 2006 and March 2012 at Erasme Hospital. FS, Fibrotest, FIB-4, aspartate aminotransferase to platelet ratio index (APRI), and Forns' scores were tested in all patients. The diagnostic accuracy of FS was 0.89 (95% confidence interval: 0.83-0.95) for the diagnosis of advanced fibrosis and 0.93 (95% confidence interval 0.90-0.97) for the diagnosis of cirrhosis. FS performed better than Fibrotest (0.81 and 0.88), APRI (0.65 and 0.75), Forns' (0.64 and 0.78), and FIB-4 (0.70 and 0.73). The optimal cut-off values of liver stiffness (LS) for predicting METAVIR fibrosis stage F≥3 and F4 disease were 10.3 and 18.0 kPa, respectively. AST showed a significant positive correlation with LS (r=0.24, P=0.001). However, exclusion of patients with AST more than 50 IU/l only lowered the LS cut-off for the diagnosis of F4 (14 vs. 18.0 kPa). FS is currently the most reliable noninvasive method for the diagnosis of advanced liver fibrosis and cirrhosis in ALD.

Primary biliary cirrhosis: an epidemiological study.

PubMed Central

Triger, D R

1980-01-01

A three-year study (1977-9) of primary biliary cirrhosis in the city of Sheffield disclosed 34 cases, a point prevalence of 54 per million population. Closer inspection showed an apparent clustering of cases, and the prevalence in relation to one water reservoir appeared to be more than ten times that of the other reservoirs. Nevertheless, analyses of the water showed no significant relevant differences between the reservoir serving areas with a high prevalence of cirrhosis and other reservoirs. Despite the inconclusive results of the water analyses, these findings do suggest that an environmental agent may be a cause of primary biliary cirrhosis and that further epidemiological studies may help to elucidate the cause. PMID:7427444

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

PubMed Central

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-01-01

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

PubMed

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-10-21

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Longitudinal associations from neurobehavioral disinhibition to adolescent risky sexual behavior in boys: direct and mediated effects through moderate alcohol consumption.

PubMed

Riggs, Nathaniel R; Tate, Eleanor B; Ridenour, Ty A; Reynolds, Maureen D; Zhai, Zu W; Vanyukov, Michael M; Tarter, Ralph E

2013-10-01

This longitudinal study tested the hypothesis that neurobehavioral disinhibition (ND) in childhood, mediated by alcohol use, portends risky sexual behavior (number of sexual partners) in midadolescence. Participants were 410 adolescent boys. Neurobehavioral disinhibition was assessed at 11.3 years of age. Frequency and quantity of alcohol use on a typical drinking occasion were assessed at 13.4 years of age at first follow-up, and sexual behavior at 16.0 years at second follow-up. Quantity of alcohol consumed on a typical drinking occasion, but not frequency of alcohol use, mediated the relation between ND and number of sexual partners. These findings indicate that number of sexual partners in midadolescence is predicted by individual differences in boys' psychological self-regulation during childhood and moderate alcohol consumption in early adolescence, and that ND may be a potential target for multi-outcome public health interventions. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Health-Related Behavior Mediates the Association Between Personality and Memory Performance in Older Adults.

PubMed

Allen, Mark S; Laborde, Sylvain; Walter, Emma E

2017-03-01

This prospective study explored the potential mediating role of health-related behavior (alcohol involvement, diet, television viewing, and physical activity) in the association between personality and change in memory performance over 2 years. A nationally representative sample of 8,376 U.K. participants aged 55 years and older (4,572 women, 3,804 men) completed self-report measures of personality and health-related behavior in 2010, and completed a memory performance task in 2010 and 2012. After removing variance associated with potential confounding variables, neuroticism and agreeableness had negative associations, and openness and conscientiousness positive associations with change in memory performance. There were no moderation effects by age, sex, education level, or ethnicity. Multiple mediator models demonstrated that physical activity, television viewing, and alcohol intake mediated associations between personality and change in memory performance. These findings provide evidence that the association between personality and memory performance in older adults can be explained, in part, through health-related behavior.

Alcohol advertising bans and alcohol abuse.

PubMed

Young, D J

1993-07-01

Henry Saffer [Saffer (1991) Journal of Health Economics 10, 65-79] concludes that bans on broadcast advertising for alcoholic beverages reduce total alcohol consumption, motor vehicle fatalities, and cirrhosis deaths. A reexamination of his data and procedures reveals a number of flaws. First, there is evidence of reverse causation: countries with low consumption/death rates tend to adopt advertising bans, creating a (spurious) negative correlation between bans and consumption/death rates. Second, even this correlation largely disappears when the estimates are corrected for serial correlation. Third, estimates based on the components of consumption--spirits, beer and wine--mostly indicate that bans are associated with increased consumption.

Glutamate Receptors within the Mesolimbic Dopamine System Mediate Alcohol Relapse Behavior.

PubMed

Eisenhardt, Manuela; Leixner, Sarah; Luján, Rafael; Spanagel, Rainer; Bilbao, Ainhoa

2015-11-25

Glutamatergic input within the mesolimbic dopamine (DA) pathway plays a critical role in the development of addictive behavior. Although this is well established for some drugs of abuse, it is not known whether glutamate receptors within the mesolimbic system are involved in mediating the addictive properties of chronic alcohol use. Here we evaluated the contribution of mesolimbic NMDARs and AMPARs in mediating alcohol-seeking responses induced by environmental stimuli and relapse behavior using four inducible mutant mouse lines lacking the glutamate receptor genes Grin1 or Gria1 in either DA transporter (DAT) or D1R-expressing neurons. We first demonstrate the lack of GluN1 or GluA1 in either DAT- or D1R-expressing neurons in our mutant mouse lines by colocalization studies. We then show that GluN1 and GluA1 receptor subunits within these neuronal subpopulations mediate the alcohol deprivation effect, while having no impact on context- plus cue-induced reinstatement of alcohol-seeking behavior. We further validated these results pharmacologically by demonstrating similar reductions in the alcohol deprivation effect after infusion of the NMDAR antagonist memantine into the nucleus accumbens and ventral tegmental area of control mice, and a rescue of the mutant phenotype via pharmacological potentiation of AMPAR activity using aniracetam. In conclusion, dopamine neurons as well as D1R-expressing medium spiny neurons and their glutamatergic inputs via NMDARs and AMPARs act in concert to influence relapse responses. These results provide a neuroanatomical and molecular substrate for relapse behavior and emphasize the importance of glutamatergic drugs in modulating relapse behavior. Here we provide genetic and pharmacological evidence that glutamate receptors within the mesolimbic dopamine system play an essential role in alcohol relapse. Using various inducible and site-specific transgenic mouse models and pharmacological validation experiments, we show that critical

Cirrhosis related chylous ascites successfully treated with TIPS.

PubMed

de Vries, G J; Ryan, B M; de Bièvre, M; Driessen, A; Stockbrugger, R W; Koek, G H

2005-04-01

We describe a patient with chylous ascites, who was extensively investigated for the cause. No malignant or lymphatic disease could be found, but a liver biopsy revealed liver cirrhosis. The chylous ascites was unsuccessfully treated with a sodium restriction diet, diuretics and a medium chain triglyceride diet. After the placement of a transjugular intrahepatic portosystemic shunt the ascites disappeared.

Minimum prices for alcohol and educational disparities in alcohol-related mortality.

PubMed

Herttua, Kimmo; Mäkelä, Pia; Martikainen, Pekka

2015-05-01

Minimum price of alcohol is one of the proposed set of alcohol policies in many high-income countries. However, the extent to which alcohol-related harm is associated with minimum prices across socioeconomic groups is not known. Using Finnish national registers in 1988-2007, we investigated, by means of time-series analysis, the association between minimum prices for alcohol overall, as well as for various types of alcoholic beverages, and alcohol-related mortality, among men and women ages 30-79 years across three educational groups. We defined quarterly aggregations of alcohol-related deaths, based on a sample including 80% of all deaths, in accordance with information on both underlying and contributory causes of death. About 62,500 persons died from alcohol-related causes during the 20-year follow-up. The alcohol-related mortality rate was more than threefold higher among those with a basic education than among those with a tertiary education. Among men with a basic education, an increase of 1% in the minimum price of alcohol was associated with a decrease of 0.03% (95% confidence interval = 0.01, 0.04%) in deaths per 100,000 person-years. Changes in the minimum prices of distilled spirits, intermediate products, and strong beer were also associated with changes in the opposite direction among men with a basic education and among women with a secondary education, whereas among the most highly educated there were no associations between the minimum prices of any beverages and mortality. Moreover, we found no evidence of an association between lower minimum prices for wine and higher rates of alcohol-related mortality in any of the population sub-groups. The results reveal associations between higher minimum prices and lower alcohol-related mortality among men with a basic education and women with a secondary education for all beverage types except wine.

The Effects of Prices on Alcohol Use and its Consequences

PubMed Central

Xu, Xin; Chaloupka, Frank J.

2011-01-01

Over the past three decades, economists and others have devoted considerable effort to assessing the impact of alcoholic-beverage taxes and prices on alcohol consumption and its related adverse consequences. Federal and State excise taxes have increased only rarely and, when adjusted for inflation, have declined significantly over the years, as have overall prices for alcoholic beverages. Yet studies examining the effects of increases of monetary prices (e.g., through raising taxes) on alcohol consumption and a wide range of related behavioral and health problems have demonstrated that price increases for alcoholic beverages lead to reduced alcohol consumption, both in the general population and in certain high-risk populations, such as heavier drinkers or adolescents and young adults. These effects seem to be more pronounced in the long run than in the short run. Likewise, price increases can help reduce the risk for adverse consequences of alcohol consumption and abuse, including drinking and driving, alcohol-involved crimes, liver cirrhosis and other alcohol-related mortality, risky sexual behavior and its consequences, and poor school performance among youth. All of these findings indicate that increases in alcoholic-beverage taxes could be a highly effective option for reducing alcohol abuse and its consequences. PMID:22330223

Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma

PubMed Central

Derambure, Céline; Coulouarn, Cédric; Caillot, Frédérique; Daveau, Romain; Hiron, Martine; Scotte, Michel; François, Arnaud; Duclos, Celia; Goria, Odile; Gueudin, Marie; Cavard, Catherine; Terris, Benoit; Daveau, Maryvonne; Salier, Jean-Philippe

2008-01-01

AIM: To look at a comprehensive picture of etiology-dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS: With a liver-oriented microarray, transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism, 12; hepatitis C, 10) and 5 controls. Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set (12 + 10) and a test set (6 + 7). RESULTS: A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism) or -2 (hepatitis C) and ontology indicated a predominant inflammatory response (alcoholism) or changes in cell cycle regulation, transcription factors and interferon responsiveness (hepatitis C). A stringent selection of 23 transcripts whose differences between etiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis. These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION: Etiology-specific abnormalities (chromosome preference; differences in transcriptomes and related functions) have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C. This may open novel avenues for differential therapies in this disease. PMID:18350606

Gastrointestinal symptoms in patients with liver cirrhosis: associations with nutritional status and health-related quality of life.

PubMed

Kalaitzakis, Evangelos; Simrén, Magnus; Olsson, Rolf; Henfridsson, Pia; Hugosson, Irene; Bengtsson, Maria; Björnsson, Einar

2006-12-01

Gastrointestinal symptoms can lead to decreased food intake and thereby increased morbidity. There is a general lack of data on the prevalence of gastrointestinal symptoms and their potential association with malnutrition and health-related quality of life (QoL) in cirrhosis. Our aim was to prospectively evaluate gastrointestinal symptoms, malnutrition, and QoL in patients with cirrhosis. Two validated questionnaires were used to measure gastrointestinal symptoms (gastrointestinal symptom rating scale (GSRS)) and health-related QoL (SF-36) in 128 consecutive cirrhotics (mean age 57 years, Child-Pugh score 8.6, MELD score 13.2) at a tertiary referral center. The results were compared with those of controls from the general population. Nutritional status was assessed by anthropometry and estimation of recent weight change. Compared to controls, cirrhotic patients showed higher gastrointestinal symptom severity (total GSRS score: 1.53, 95% CI 1.50-1.55 versus 2.21, 95% CI 2.04-2.38) and profound reductions in the SF-36 physical (47.0 95% CI 45.0-49.0 versus 37.9, 95% CI 35.7-40.1) and mental component summary scores (51.0 95% CI 49.0-53.0 versus 39.2 95% CI 36.7-41.6). There were no significant differences in any GSRS domain between patients with and those without malnutrition. Multivariate analysis showed that gastrointestinal symptom severity was associated with the Child-Pugh score (beta = 0.10, r<0.05), daily lactulose use (beta = 0.65, p<0.005), and the presence of gastrointestinal comorbidities (beta = 0.51, p<0.05). Negative weight change (beta = -0.72, p<0.05) and the SF-36 physical (beta = -4.26, p<0.005) and mental (beta = -4.53, p<0.005) summaries were independently related to gastrointestinal symptom severity. Patients with cirrhosis show increased severity of gastrointestinal symptoms, which are associated with recent weight loss and impaired health-related QoL. The severity of gastrointestinal symptoms seems to be related to the severity of cirrhosis.

The relationship of parental reinforcement of media messages to college students' alcohol-related behaviors.

PubMed

Weintraub Austin, Erica; Chen, Yin Ju

2003-01-01

Although alcohol consumption is a problem on the college campus, beliefs and behaviors predictive of alcohol use are in development in children as young as third grade. Because they develop partially in response to interpretations of media messages, for which parents can have an influence, this study examined how college students' (N=300) recollections of parental reinforcement of media messages associated with alcohol-related beliefs and behaviors. Structural equation modeling showed that recalled positive mediation negatively predicted skepticism, and positively predicted desirability and expectancies. Desirability of media messages predicted more positive norms perceptions, and a lack of skepticism predicted more positive expectancies. With age of first experimentation controlled, expectancies predicted heavier current drinking behavior. Norms did not predict behavior, and positive mediation did not predict norms. The study concludes that to the extent parental communication leads adolescents to interpret media messages less skeptically, they encourage adolescents to find alcohol portrayals appealing. This in turn appears to lead toward more risky behaviors. The results suggest that college-based anti-alcohol campaigns can benefit by acknowledging the appeal of competing messages and by including parents as a campaign target.

Liver cirrhosis in England-an observational study: are we measuring its burden occurrence correctly?

PubMed

Ratib, Sonia; West, Joe; Fleming, Kate M

2017-07-13

Mortality due to liver disease (of which cirrhosis is the end stage) is increasing more than any other chronic condition in the UK. This study aims to demonstrate that (1) exclusive reliance on mortality rates may not reveal the true burden of liver cirrhosis, and (2) diverse use of diagnostic coding may produce misleading estimates. Observational study. The Office for National Statistics death registry was interrogated to investigate liver cirrhosis mortality trends in England and Wales from 1968 to 2011. Standardised mortality trends according to three different definitions of liver cirrhosis based on the specificity of diagnostic codes were calculated: 1 (chronic liver diseases), 2 (alcoholic and unspecified cirrhosis only) and 3 (cirrhosis as end-stage liver disease). The mortality trends were compared with incidence rates established in a previous population-based study (based on definition 3), from 1998 to 2009, to investigate discrepancies between these two measures. Over the study period, the overall standardised liver cirrhosis mortality rates were 8.8, 5,1 and 5.4 per 100 000 person-years for definitions 1, 2 and 3, respectively. The mortality rates for definition 3 in 1998 and 2009 were 6.2 and 5.9 per 100 000 person-years, respectively; while the equivalent incidence rates were at least threefold and sixfold higher: 23.4 and 35.9 per 100 000 person-years, respectively. This discrepancy between incidence and mortality rates was also at least threefold in men and women separately and across age groups. Mortality rates underestimated the incidence of liver cirrhosis by at least threefold between 1998 and 2009 and varied with differing definitions of disease. Mortality data should not be used exclusively as an indicator for the occurrence of liver cirrhosis in the population. Routinely collected healthcare data are available to measure occurrence of this disease. Careful consideration should be taken when selecting diagnostic codes for cirrhosis. �

PTSD symptoms and pain in Canadian military veterans: the mediating roles of anxiety, depression, and alcohol use.

PubMed

Irwin, Kara C; Konnert, Candace; Wong, May; O'Neill, Thomas A

2014-04-01

Symptoms of posttraumatic stress disorder (PTSD) and pain are often comorbid among veterans. The purpose of this study was to investigate to what extent symptoms of anxiety, depression, and alcohol use mediated the relationship between PTSD symptoms and pain among 113 treated male Canadian veterans. Measures of PTSD, pain, anxiety symptoms, depression symptoms, and alcohol use were collected as part of the initial assessment. The bootstrapped resampling analyses were consistent with the hypothesis of mediation for anxiety and depression, but not alcohol use. The confidence intervals did not include zero and the indirect effect of PTSD on pain through anxiety was .04, CI [.03, .07]. The indirect effect of PTSD on pain through depression was .04, CI [.02, .07]. These findings suggest that PTSD and pain symptoms among veterans may be related through the underlying symptoms of anxiety and depression, thus emphasizing the importance of targeting anxiety and depression symptoms when treating comorbid PTSD and pain patients. © 2014 International Society for Traumatic Stress Studies.

[Clinical features of liver cirrhosis complicated by portal vein thrombosis and related risk factors].

PubMed

Lin, G S; Xu, Q; Zhao, S Y; Zhang, Y X

2016-07-20

Objective: To investigate the clinical features of patients with liver cirrhosis complicated by portal vein thrombosis (PVT) and related risk factors. Methods: A total of 65 patients with liver cirrhosis complicated by PVT who were diagnosed and treated from June 2013 to June 2015 were enrolled as PVT group, and 70 cirrhotic patients without PVT were enrolled as controls (non-PVT group). The data collected included general information, results of laboratory examination, imaging findings, clinical manifestations, and complications. The clinical features were compared between the two groups, and related risk factors were screened out. Results: There were no significant differences between the PVT group and non-PVT group in age, sex, nation, etiology, white blood cell count, platelet count, international normalized ratio, activated partial thromboplastin time, fibrinogen, serum creatinine, total bilirubin, and the diameter of the splenic vein (all P > 0.05), while between these two groups, there were significant differences in D-dimer (1.87±1.45 mg/ml vs 0.55±0.58 mg/ml, P < 0.05), fibrinogen degradation product (FDP) level (18.57±19.46 μg/ml vs 5.45±6.00 μg/ml, P < 0.05), hemoglobin (99.32±26.73 g/L vs 112.64±25.03 g/L, P < 0.05), albumin (28.51±5.19 g/L vs 33.07±7.94 g/L, P < 0.05), the diameter of the portal vein (12.53±2.70 mm vs 11.17±1.79 mm, P < 0.05), spleen thickness (5.12±0.95 cm vs 4.56±0.83 cm, P < 0.05), spleen length (15.35±3.21 cm vs 13.86±2.82 cm, P < 0.05), and Child-Pugh score (7.66±2.06 vs 6.93±1.87, P < 0.05). The two groups showed no significant differences in diarrhea, ileus, hepatorenal syndrome, and hepatic encephalopathy ( P > 0.05), but showed significant differences in abdominal pain (18 vs 7 cases, P < 0.05), fever (17 vs 4 cases, P < 0.05), esophageal variceal bleeding (22 vs 9 cases, P < 0.05), and spontaneous peritonitis (24 vs 12 cases, P < 0.05). D-dimer (OR = 4.290, P < 0.000) and mean platelet volume (OR = 1.294, P

Non-Alcoholic Fatty Liver Disease in HIV Infection.

PubMed

Macías, Juan; Pineda, Juan A; Real, Luis M

2017-01-01

Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

Negative urgency mediates the relationship between childhood maltreatment and problems with alcohol and cannabis in late adolescence

PubMed Central

Wardell, Jeffrey D.; Strang, Nicole M.; Hendershot, Christian S.

2017-01-01

Background Childhood maltreatment is an important risk factor for problems with alcohol and other drugs such as cannabis. Although this link has been well established, the mechanisms in this association require further study. High levels of impulsivity and difficulties with emotion regulation are often associated with childhood maltreatment. Negative urgency – an emotion-based facet of impulsivity – is a strong predictor of substance use problems and may be a particularly relevant facet of impulsivity in the link between childhood maltreatment and alcohol and cannabis outcomes. However, few studies have examined the specific mediational pathway from childhood maltreatment to alcohol and cannabis problems through negative urgency. Objectives We tested the hypothesis that the associations between history of childhood maltreatment and current alcohol and cannabis problems would be mediated by negative urgency, but not other facets of impulsivity. Methods Participants (N=232), who were in late adolescence (mean age=19.75), completed self-report measures of different facets of impulsivity, past childhood maltreatment, and current alcohol and cannabis use and problems. Results In analyses including several facets of impulsivity as simultaneous mediators, negative urgency was the only facet to mediate the associations of childhood maltreatment severity with alcohol and cannabis problems. Conclusions These findings provide support for negative urgency as a unique mediator of the association between childhood maltreatment and both alcohol and cannabis problems, suggesting that future work on mechanisms in this association should focus on mood-based impulsivity. PMID:26774820

Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis.

PubMed

Caussy, Cyrielle; Soni, Meera; Cui, Jeffrey; Bettencourt, Ricki; Schork, Nicholas; Chen, Chi-Hua; Ikhwan, Mahdi Al; Bassirian, Shirin; Cepin, Sandra; Gonzalez, Monica P; Mendler, Michel; Kono, Yuko; Vodkin, Irine; Mekeel, Kristin; Haldorson, Jeffrey; Hemming, Alan; Andrews, Barbara; Salotti, Joanie; Richards, Lisa; Brenner, David A; Sirlin, Claude B; Loomba, Rohit

2017-06-30

The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis. This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE). The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438). Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients. 140084. National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

Alcohol and alcohol-related harm in China: policy changes needed

PubMed Central

Tang, Yi-lang; Xiang, Xiao-jun; Wang, Xu-yi; Cubells, Joseph F; Babor, Thomas F

2013-01-01

Abstract In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China’s policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China’s current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization’s global strategy to reduce the harmful use of alcohol. PMID:23599550

Association between diabetes mellitus and cirrhosis mortality: the Singapore Chinese Health Study.

PubMed

Goh, George Boon-Bee; Pan, An; Chow, Wan-Cheng; Yuan, Jian-Min; Koh, Woon-Puay

2017-02-01

Diabetes mellitus has been linked to cirrhosis-related mortality in Western populations, but less is known about this relationship in Asian populations. We studied the impact of diabetes on the risk of cirrhosis mortality in a population-based cohort among Chinese in Singapore. We used data collected and analysed from the Singapore Chinese Health Study, a prospective community-based cohort of 63 275 subjects aged 45-74 years during enrolment between 1993 and 1998. Information on diet, lifestyle and medical history was collected via structured questionnaire. Mortality cases from cirrhosis in the cohort were identified via linkage with nationwide death registry up to 31 December 2014. Cox proportional regression models were used to estimate the associations with adjustment for risk factors of cirrhosis. After a mean follow-up of 16.9 years, there were 133 deaths from cirrhosis. Diabetes was associated with an increased risk of cirrhosis mortality (hazard ratio [HR]: 2.80; 95% confidence interval [CI]: 2.04-3.83), and for both viral (HR: 2.20; 95% CI: 1.18-4.11) and non-viral hepatitis-related cirrhosis mortality (HR: 3.06; 95% CI: 2.13-4.41). The association between diabetes and non-viral hepatitis-related cirrhosis mortality was stronger among participants of body mass index (BMI) less than 23 kg/m 2 (HR: 7.11; 95% CI: 3.42-14.79) compared to heavier individuals (HR: 2.28; 95% CI: 1.20-4.35) (P interaction =0.02). Diabetes is a risk factor for cirrhosis mortality, especially for non-viral hepatitis-related cirrhosis in population with BMI considered low or normal in Asia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.

PubMed

Privitera, Graziella; Spadaro, Luisa; Marchisello, Simona; Fede, Giuseppe; Purrello, Francesco

2018-01-01

Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver cirrhosis and to address the need of a better prognostic stratification of patients, including lipoprotein profile assessment. Low levels of lipoproteins are usual in cirrhosis. Much evidence supports the prognostic role of hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia represents an independent predictor of survival in cirrhosis. In cirrhotic patients, lipoprotein impairment is associated with several complications: infections, malnutrition, adrenal function, and spur cell anemia. Alterations of liver function are associated with modifications of circulating lipids. Decreased levels of lipoproteins significantly impact the survival of cirrhotic patients and play an important role in the pathogenesis of some cirrhosis-related complications.

Mediation-moderation analysis of problematic alcohol use: the roles of urgency, drinking motives, and risk/benefit perception.

PubMed

Coskunpinar, Ayca; Cyders, Melissa A

2012-07-01

The goal of the current study is to examine how urgency, drinking motives, and risk/benefit perception concurrently influence problematic alcohol consumption in young adults. Participants were 281 young adults enrolled in large, public US mid-western university. The mean age of the sample was 19.81 (SD=1.82) and 79.7% of the sample was female and 84.7% of the sample was Caucasian. A series of moderated-mediation analyses indicated the following: The relationship between negative urgency and alcohol use was mediated through coping motives, and this relationship between coping motives and alcohol use was moderated by benefit perception. The relationship between positive urgency and alcohol use was mediated through enhancement motives, and this relationship between enhancement motives and alcohol use was moderated by benefit perception. This study suggests that modifying perceptions about the benefits of alcohol and drinking motives could be viable prevention and/or treatment strategy in this population, especially among those who exhibit urgent behaviors. Published by Elsevier Ltd.

Is Readiness to Change Drinking Related to Reductions in Alcohol Use and Consequences? A Week-to-Week Analysis

PubMed Central

Merrill, Jennifer E.; Wardell, Jeffrey D.; Read, Jennifer P.

2015-01-01

Objective: The literature on whether readiness to change (RTC) alcohol use translates into actual change among college students is both limited and mixed, despite the importance of understanding naturalistic change processes. Few studies have used fine-grained, prospective data to examine the link between RTC and subsequent drinking behavior, and alcohol consequences in particular. The present study involves tests of whether (a) intraindividual changes in RTC are negatively associated with alcohol use and alcohol-related consequences from week to week, (b) the effect of RTC on use and consequences is direct versus mediated by change in alcohol use, and (c) the association between RTC and drinking behavior is moderated by gender. Method: Participants were 96 college student drinkers who completed a baselinesurvey and 10 weekly web-based assessments of RTC, alcohol use, and consequences. Results: Hierarchical linear models indicated that, as hypothesized, reporting greater RTC on a given week (relative to one’s average level of RTC) was negatively associated with alcohol use (measured by either drinks per week or frequency of heavy episodic drinking) and alcohol consequences the following week. Changes in use fully mediated the relationship between RTC and consequences. The prospective association between RTC and both alcohol use and consequences did not differ by gender. Conclusions: Findings suggest that higher RTC translates into short-term reductions in alcohol use and in turn alcohol consequences, and highlight important avenues for future research. PMID:26402360

Mediation by peer violence victimization of sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors: pooled youth risk behavior surveys.

PubMed

Rosario, Margaret; Corliss, Heather L; Everett, Bethany G; Russell, Stephen T; Buchting, Francisco O; Birkett, Michelle A

2014-06-01

We examined the role of adolescent peer violence victimization (PVV) in sexual orientation disparities in cancer-related tobacco, alcohol, and sexual risk behaviors. We pooled data from the 2005 and 2007 Youth Risk Behavior Surveys. We classified youths with any same-sex sexual attraction, partners, or identity as sexual minority and the remainder as heterosexual. We had 4 indicators of tobacco and alcohol use and 4 of sexual risk and 2 PVV factors: victimization at school and carrying weapons. We stratified associations by gender and race/ethnicity. PVV was related to disparities in cancer-related risk behaviors of substance use and sexual risk, with odds ratios (ORs) of 1.3 (95% confidence interval [CI] = 1.03, 1.6) to 11.3 (95% CI = 6.2, 20.8), and to being a sexual minority, with ORs of 1.4 (95% CI = 1.1, 1.9) to 5.6 (95% CI = 3.5, 8.9). PVV mediated sexual orientation disparities in substance use and sexual risk behaviors. Findings were pronounced for adolescent girls and Asian/Pacific Islanders. Interventions are needed to reduce PVV in schools as a way to reduce sexual orientation disparities in cancer risk across the life span.

Cirrhosis Diagnosis and Liver Fibrosis Staging: Transient Elastometry Versus Cirrhosis Blood Test.

PubMed

Calès, Paul; Boursier, Jérôme; Oberti, Frédéric; Bardou, Derek; Zarski, Jean-Pierre; de Lédinghen, Victor

2015-07-01

Elastometry is more accurate than blood tests for cirrhosis diagnosis. However, blood tests were developed for significant fibrosis, with the exception of CirrhoMeter developed for cirrhosis. We compared the performance of Fibroscan and CirrhoMeter, and classic binary cirrhosis diagnosis versus new fibrosis staging for cirrhosis diagnosis. The diagnostic population included 679 patients with hepatitis C and liver biopsy (Metavir staging and morphometry), Fibroscan, and CirrhoMeter. The prognostic population included 1110 patients with chronic liver disease and both tests. Binary diagnosis: AUROCs for cirrhosis were: Fibroscan: 0.905; CirrhoMeter: 0.857; and P=0.041. Accuracy (Youden cutoff) was: Fibroscan: 85.4%; CirrhoMeter: 79.2%; and P<0.001. Fibrosis classification provided 6 classes (F0/1, F1/2, F2±1, F3±1, F3/4, and F4). Accuracy was: Fibroscan: 88.2%; CirrhoMeter: 88.8%; and P=0.77. A simplified fibrosis classification comprised 3 categories: discrete (F1±1), moderate (F2±1), and severe (F3/4) fibrosis. Using this simplified classification, CirrhoMeter predicted survival better than Fibroscan (respectively, χ=37.9 and 19.7 by log-rank test), but both predicted it well (P<0.001 by log-rank test). Comparison: binary diagnosis versus fibrosis classification, respectively, overall accuracy: CirrhoMeter: 79.2% versus 88.8% (P<0.001); Fibroscan: 85.4% versus 88.2% (P=0.127); positive predictive value for cirrhosis by Fibroscan: Youden cutoff (11.1 kPa): 49.1% versus cutoffs of F3/4 (17.6 kPa): 67.6% and F4 classes (25.7 kPa): 82.4%. Fibroscan's usual binary cutoffs for cirrhosis diagnosis are not sufficiently accurate. Fibrosis classification should be preferred over binary diagnosis. A cirrhosis-specific blood test markedly attenuates the accuracy deficit for cirrhosis diagnosis of usual blood tests versus transient elastometry, and may offer better prognostication.

Renal water handling in rats with decompensated liver cirrhosis.

PubMed

Jonassen, T E; Christensen, S; Kwon, T H; Langhoff, S; Salling, N; Nielsen, S

2000-12-01

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg. kg(-1). h(-1)) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (delta V/GFR; +24%) and fractional distal water excretion (delta V/C(Li); +46%) were significantly increased in the cirrhotic rats, where V is flow rate and delta is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

Moderating Effects of a Craving Intervention on the Relation between Negative Mood and Heavy Drinking Following Treatment for Alcohol Dependence

ERIC Educational Resources Information Center

Witkiewitz, Katie; Bowen, Sarah; Donovan, Dennis M.

2011-01-01

Objective: Negative affect is a significant predictor of alcohol relapse, and the relation between negative affect and drinking has been shown to be strongly mediated by alcohol craving. Thus, targeting craving during treatment could potentially attenuate the relation between negative affect and drinking. Method: The current study is a secondary…

Motives to drink or not to drink: longitudinal relations among personality, motives, and alcohol use across adolescence and early adulthood.

PubMed

Anderson, Kristen G; Briggs, Kristen E L; White, Helene R

2013-05-01

Adolescent selective intervention programs for alcohol have focused on the identification of youth at risk as a function of personality and associated alcohol-related cognitions. Research into the role of personality, drinking motivations, and alcohol-related outcomes has generally focused exclusively on motives to drink. We expand on this literature by focusing on both motives to drink and motives not to drink across time from adolescence to early adulthood in a community sample. Using 3 waves of data from 3 cohorts from the Rutgers Health and Human Development Project (n = 1,380; 49.4% women), we modeled the influence of baseline alcohol consumption, disinhibition (DIS), and harm avoidance (ages 15, 18, and 21 years) on drinking motives and motives not to drink 3 years later (ages 18, 21, and 24 years) and alcohol use and drinking-related problems 7 years subsequently (ages 25, 28, and 31 years). Path analytic models were relatively invariant across cohort. Across cohorts, DIS and baseline alcohol consumption related to later positive reinforcement drinking motives, but less consistency was found for the prediction of negative reinforcement motives to drink. While positive reinforcement motives were associated with greater alcohol consumption and problems 7 years later, negative reinforcement motives were generally associated with problems alone. Positive reinforcement motives for drinking mediated relations between baseline consumption and later consumption. However, results were mixed when considering DIS as a predictor and drinking problems as an outcome. Similarly, personality and baseline consumption related to later motives not to drink and such motives predicted subsequent alcohol-related problems. However, mediation was not generally supported for pathways through motives to abstain. The results of this study replicate and extend previous longitudinal findings with youth and add to the growing literature on motivations not to engage in alcohol use

Alcoholism: A systemic proinflammatory condition

PubMed Central

González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

2014-01-01

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver. PMID:25356029

Alcohol prevention strategies on college campuses and student alcohol abuse and related problems.

PubMed

Ringwalt, Christopher L; Paschall, Mallie J; Gitelman, Amy M

2011-01-01

This study examined the relationship between colleges' alcohol abuse prevention strategies and students' alcohol abuse and related problems. Alcohol prevention coordinators and first year students in 22 colleges reported whether their schools were implementing 48 strategies in six domains, and students (N = 2041) completed another survey concerning their use of alcohol and related consequences. Colleges were most likely to prevent alcohol use in public places on campus and the delivery and use of kegs. Four alcohol prevention domains were inversely associated with at least one of five outcomes related to student alcohol abuse or related consequences, and the alcohol policy and enforcement domain was inversely associated with all outcomes. Colleges should pay particular attention to strategies related to policy and enforcement.