Lifetime Daily Alcohol Intake Research Articles

Alcohol intake affects AD and LATE: A telltale lifestyle from two large‐scale datasets

AbstractBackgroundAD is not caused by a single factor but by a variety of factors, of which factors are considered to be important. At present, the factors affecting LATE are largely unknown; in particular, the factors that distinguish AD from LATE are yet to be identified.MethodWe leveraged an innovative integrated feature selection‐based algorithm of preprocessing, feature selection, and validation, abbreviated as PFV (Figure 1), to identify important environmental risk factors differentiating subjects with LATE and/or AD from Control with healthy cognition on significantly imbalanced data. PFV was applied on two existing large‐scale datasets, i.e., a discovery dataset (ROSMAP) and a validation dataset (NACC), which comprised subjects with LATE and AD, and Control. Independent validation across datasets was performed in NACC by using chi‐square test and logistic regression analysis.ResultWe retrospectively analyzed the data of 508 subjects in ROSMAP for discovery and 9,256 subjects in NACC for independent validation. In ROSMAP, the sets of risk factors that we identified were usually small. For example, for LATE vs. AD scenario, compared to using all variates, 2 risk factors were identified for the whole cohort with an improvement in AUROC of about 7%, 1 risk factor was identified for Male subpopulation with an improvement of about 26%, 3 risk factors were identified for Female subpopulation with an improvement of about 7%, 2 risk factors were identified for White subpopulation with an improvement of about 6%, and 3 risk factors were identified for >85 subpopulation with an improvement of about 9% (Figure 2 and Table 2). And our results suggest that alcohol intake and living activities are significant risk factors for LATE; for instance, in LATE vs. Control scenario, lifetime daily alcohol intake is the common risk factor for the whole cohort (p‐value: 3.14e‐03), Male subpopulation (p‐value: 4.00e‐02), White subpopulation (p‐value: 1.14e‐03), and >85 subpopulation (p‐value: 4.11e‐03). In NACC, statistical analyses validate the role of alcohol consumption on AD and LATE.ConclusionWe found that alcohol intake affects AD than LATE, which was first identified on the discovery dataset ROSMAP and then further validated on the across dataset NACC.

S11 * ALCOHOL AS A MODULATOR OF LIVER DISEASE PROGRESSION ESBRA & EASL JOINT SYMPOSIUM

S11 * ALCOHOL AS A MODULATOR OF LIVER DISEASE PROGRESSION ESBRA & EASL JOINT SYMPOSIUM

Medication treatment of alcohol use disorders in veterans with Hepatitis C

Hepatitis C viral infection (HCV) is the most common chronic blood borne viral infection in the world and in the United States affects approximately 1.8% of the general population. The prevalence of hepatitis C viral infection (HCV) is 3-4 times higher among veterans who use VA services than the general population rate of 1.8% and is estimated to be approximately 5 to 6%. A national VA study found that over 75% of veterans had some Substance Use Disorder. At the Portland VAMC, 57.6% (n = 783) of veterans with HCV recently seen in the hepatology clinic reported consuming alcohol in the past year and approximately 25% reported heavy alcohol use (AUDIT C score of 4 or greater). Alcohol use and HCV are thought to act synergistically to accelerate liver damage and cirrhosis. Several studies show heavy alcohol consumption increases the risk of fibrosis progression as well as the risk of end stage liver disease and cirrhosis in HCV patients. Among them Corrao and Arico (1998) found, among all patients who do not drink alcohol, HCV-infected patients are 9.2 times more likely to develop liver cirrhosis than non-HCV-infected patients. They also found that there is a dose-dependent relationship between lifetime daily alcohol intake, HCV infection, and risk of developing cirrhosis. Compared to HCV patients who do not drink, the risk of cirrhosis was three times higher in HCV patients who drank 75 to 100 grams per day, 16 times higher in HCV patients who drank ≥175 grams per day of alcohol than HCV patients who did not drink and over 140 times higher than people who did not have HCV or drink alcohol. Effective treatments for alcohol use have not been studied in patients chronically infected with HCV and current FDA-approved medications for AUD can adversely affect the liver and are generally not well tolerated. The presentation will review current FDA -approved as well as off-label use medication studies for Alcohol Use Disorders and their utility for people who have hepatitis C and co-morbid Alcohol Use Disorders. The various treatment options will be discussed.

Correlation of alcohol consumption with liver histological features in non-cirrhotic patients

The association between alcohol consumption and the risk of liver disease remains unclear. The aim of our study was to determine liver morphological features directly related to the mean lifetime daily alcohol intake (LTDAI) in non-cirrhotic patients. Medical records of all consecutive patients who reported alcohol consumption up to the time of hospital admission and who had undergone a liver biopsy in the Gastroenterology Unit of the University Hospital Centre of Tirana (Albania), were reviewed. Patients with established cirrhosis and/or with other possible causes of liver damage were excluded by the study. The histological features revealed in the biopsy samples of 51 non-cirrhotic patients were: steatosis in 46 patients (91%), six of whom (13%) showed also alcoholic foamy degeneration; alteration of hepatocytes in 40 patients (78%), diffuse mononuclear inflammation in 37 patients (73%), polymorphonuclear inflammation in 11 patients (22%) and perivenular fibrosis in 18 patients (35%). Diffuse steatosis was directly correlated with alcohol consumption (P<0.01). No association was found between alcohol consumption and the presence of degenerative alterations of hepatocytes, Mallory bodies or hepatocellular necrosis. Fibrosis was more prevalent in patients who reported a LTDAI > or = 80 g in comparison with patients who reported a LTDAI > or = 40 to <80 g (48% vs 25%; P<0.05). In non-cirrhotic patients liver steatosis and fibrosis were more common features among patients who reported a higher alcoholic consumption, but no clear-cut association between typical histological features of alcoholic liver disease and alcohol consumption was found.

Alcohol and hepatocellular carcinoma

More than 18 million adults in the United States abuse alcohol, a prevalence 5 times higher than that of hepatitis C. Chronic alcohol use of greater than 80 g/day for more than 10 years increases the risk for hepatocellular carcinoma (HCC) approximately 5-fold; alcohol use of less than 80 g/day is associated with a nonsignificant increased risk for HCC. The risk for HCC in decompensated alcohol induced cirrhosis approaches 1% per year. The risk does not decrease with abstinence, and HCC can occur in a noncirrhotic liver. Alcohol use in chronic hepatitis C doubles the risk for HCC as compared with the risk in hepatitis C alone. Furthermore, there may be synergism between alcohol and hepatitis C in the development of HCC, and in these patients HCC may occur at an earlier age and the HCC may be histologically more advanced. Studies in the United States and Italy suggest that alcohol is the most common cause of HCC (accounting for 32%-45% of HCC). The mechanisms by which alcohol causes HCC are incompletely understood, but may include chromosomal loss, oxidative stress, a decreased retinoic acid level in the liver, altered DNA methylation, and genetic susceptibility. Alcohol use is increasing in many countries, suggesting that alcohol will continue to be a common cause of HCC throughout the world.

Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis

Although alcohol intake and hepatitis C virus (HCV) infection are the major determinants of liver cirrhosis (LC) in Western countries, the joint effect of these two factors on LC risk has not yet been adequately studied. We used data from two hospital-based case-control studies performed in Italy. Cases were 285 cirrhotic patients admitted for the first time to district hospitals for liver decompensation. Controls were 417 patients admitted during the same period, and in the same hospitals as the cases, for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Serum HCV antibodies (anti-HCV) were detected using a second-generation test and recombinant immunoblotting assay. We found a dose-effect relationship between LDAI and the risk of LC in both anti-HCV-negative and -positive subjects. Considering the extreme LDAI categories (LDAI = 0 g, lifetime teetotalers, and LDAI = 175 g), the LC odds ratios increased from 1.0 (reference category) to 15.0 (95% CI, 7.1-31.7) and from 9.2 (95% CI, 2.0-43.2) to 147.2 (95% CI, 42.1-514.3) in anti-HCV-negative and -positive patients respectively. The interaction between LDAI and HCV showed an additive structure for LDAI 125 g/day. Alcohol intake and HCV infection are independent risk factors for symptomatic liver cirrhosis, each being sufficient to induce the disease. In subjects with high alcohol intake, the coexistence of HCV infection multiplies the alcohol-associated risk of cirrhosis. In subjects with low alcohol intake, other factors could be involved.

Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis.

Although alcohol intake and hepatitis C virus (HCV) infection are the major determinants of liver cirrhosis (LC) in Western countries, the joint effect of these two factors on LC risk has not yet been adequately studied. We used data from two hospital-based case-control studies performed in Italy. Cases were 285 cirrhotic patients admitted for the first time to district hospitals for liver decompensation. Controls were 417 patients admitted during the same period, and in the same hospitals as the cases, for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Serum HCV antibodies (anti-HCV) were detected using a second-generation test and recombinant immunoblotting assay. We found a dose-effect relationship between LDAI and the risk of LC in both anti-HCV-negative and -positive subjects. Considering the extreme LDAI categories (LDAI = 0 g, lifetime teetotalers, and LDAI = 175 g), the LC odds ratios increased from 1.0 (reference category) to 15.0 (95% CI, 7.1-31.7) and from 9.2 (95% CI, 2.0-43.2) to 147.2 (95% CI, 42.1-514.3) in anti-HCV-negative and -positive patients respectively. The interaction between LDAI and HCV showed an additive structure for LDAI < 50 g/day and a multiplicative structure for consumption > 125 g/day. Alcohol intake and HCV infection are independent risk factors for symptomatic liver cirrhosis, each being sufficient to induce the disease. In subjects with high alcohol intake, the coexistence of HCV infection multiplies the alcohol-associated risk of cirrhosis. In subjects with low alcohol intake, other factors could be involved.

Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis. Collaborative Groups for the Study of Liver Diseases in Italy.

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables. a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.

Is alcohol a risk factor for liver cirrhosis in HBsAg and anti-HCV negative subjects?

Background/Aims: In order to evaluate the association between alcohol intake and the risk of liver cirrhosis in the absence of B and C hepatitis viruses, we analyzed data from three hospital-based case-control studies performed in various Italian areas. Methods: From the case and control series we excluded HBsAg and/or anti-HCV positive patients. Cases were 221 cirrhotic patients admitted for the first time to hospital for liver decompensation. Controls were 614 patients admitted to the same hospitals during the same period as the cases for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Results: We found a dose-effect relationship between LDAI and the risk of liver cirrhosis (LC). Considering the extreme LDAI categories (LDAI=0 g: lifetime teetotallers and LDAI≥100 g), the LC odds ratio (OR) increased from 1.0 (reference category) to 44.7 (95% confidence interval: 95% CI: 20.0–99.9). An increased risk of LC associated with the female gender independent of alcohol consumption was also observed (OR=2.9; 95% CI: 1.8–4.6). Conclusions: Alcohol intake acts as a risk factor for symptomatic liver cirrhosis also in the absence of HBV and/or HCV infection. Besides alcohol and viruses, some unknown gender-related factors might be involved in the occurrence of the disease.

Female Sex and the Risk of Liver Cirrhosis

Corrao G, Aricò S, Zambon A, Torchio P, di Orio F, Collaborative Groups for the Study of Liver Diseases in Italy. Female sex and the risk of liver cirrhosis. Scand J Gastroenterol 1997 32:1174–1180.Background: Evidence on gender-related differences in susceptibility to alcohol-induced liver diseases is questionable with regard to both methodologic and clinical aspects. With the aim to assess the role of gender in the risk of liver cirrhosis, independently and in combination with known risk factors, data from three case-control studies performed in various Italian areas were analysed. Methods: The cases were 462 cirrhotic patients (300 men and 162 women) admitted for the first time to hospital for liver decompensation. Controls were 651 patients (355 men and 296 women) admitted to the same hospitals during the same period as the cases, for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake. Results: A significant and independent associations between alcohol intake, chronic hepatitis B and C virus infections, and the risk of liver cirrhosis was observed. The effect of alcohol intake was multiplicatively increased in women. The odds ratio (OR) increased from 1.0 (reference category: men, lifetime abstainers) to 31.4 (95% confidence interval (CI), 10.3–95.8) in men drinking more than 100 g/day of alcohol, and from 2.2 (95% CI, 1.0–7.1) in abstaining women to 44.8 (95% CI, 8.2–224.0) in women drinking more than 100 g/day of alcohol. An increased risk of liver cirrhosis associated with female gender independently of alcohol consumption and virus infection was also observed. Conclusions: A higher susceptibility to alcohol-induced liver diseases was confirmed for women, and an independent effect of female sex on the risk of cirrhosis was observed. Besides alcohol and viruses, some unknown gender-related factor might then be involved in the occurrence of the disease.

The measure of life-time alcohol consumption in patients with cirrhosis: reproducibility and clinical relevance.

Our aims were to design a reproducible method of measuring life-time alcohol consumption in patients with cirrhosis, and to assess the risk of liver decompensation associated with alcohol intake using a case-control design and a multivariate analysis. We studied 439 patients ("cases") with decompensated cirrhosis, and 233 with compensated cirrhosis ("controls"). Mean life-time daily amount and duration of alcohol intake were measured by a standardized questionnaire, whose reproducibility, assessed by interviewing 75 relatives, was 70% for daily alcohol intake and 84% for duration of intake. Better reproducibility was found by re-interviewing patients at discharge from hospital. Daily alcohol intake was significantly higher in males, younger patients and patients with liver decompensation. After stratification according to the average life-time daily alcohol intake, we found a significant increase in the risk of liver decompensation from 125 g ethanol intake per day onwards. No association was found between duration of alcohol intake and risk of liver decompensation. We conclude that alcohol intake can be reliably and reproducibly measured: in patients with cirrhosis, increased alcohol intake is associated with increased risk of liver decompensation, with a significant dose-effect above a daily intake of 125 g ethanol.

The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption

In order to assess the interaction between alcohol intake, tobacco smoking and coffee con sumption in determining the risk of liver cirrhosis we carried out a hospital-based case-control study involving 115 patients at their first diagnosis of cirrhosis and 167 control patients consecutively enrolled in the General Hospitals of the Province of L'Aquila (Central Italy). The mean life-time daily alcohol intake (as g ethanol consumed daily) was measured by direct patient interviews, whose reproducibility was >0.80 and similar for cases and controls, as checked by interviewing the relatives of a sample of 50 cases and 73 controls. During the same patient's interview we also measured the mean consumption of coffee (daily number of cups of filtered coffee) and tobacco (life-time daily number of cigarettes smoked). A dose-effect relationship on the risk of cirrhosis was present both for alcohol intake — for which the risk was significantly increased above 100 g of daily intake — and for cigarette consumption. The latter did not however improve the goodness-of-fit of a logistic regression model including alcohol intake as covariate. By contrast, coffee consumption had a protective effect on the risk of cirrhosis and significantly improved the goodness-of-fit of such a model. Abstaining from coffee consumption determined both a significantly increased risk of cirrhosis, even for daily alcohol intake below 100 g, and a multiplicative effect with alcohol intake on this risk. In patients drinking ⩾101 g ethanol daily the relative risk increased from 5.5 (95% confidence interval: 1.4–22.0) for coffee consumers to 10.8 (95% confidence interval: 1.3–58.1) for coffee abstainers. We conclude that: (1) tobacco smoking is likely to be a faint risk factor for cirrhosis, and studies on wider patients series should be performed for confirmation; (2) coffee drinking is associated with a reduced risk of cirrhosis. Whether coffee contains some hitherto unknown protective substances, or is just a marker of other life-style or dietary protective factors, deserves further clarification.

Monitoring oxidative damage in patients with liver cirrhosis and different daily alcohol intake.

This study looked at the possible association between alcohol abuse and free radical mediated oxidative injury by examining the presence of oxidative damage, as monitored by erythrocyte malonildialdehyde and plasma lipid hydroperoxides, in patients with liver cirrhosis and different lifetime daily alcohol intake. All patients with an alcohol intake above 100 g/day (ALC) showed concentrations of malonildialdehyde and lipid hydroperoxide on average four to fivefold higher than cirrhotic patients with alcohol intake below 100 g/day (NAC) or healthy controls. Further subgrouping of ALC patients showed that those with alcohol intake ranging between 100 and 200 g/day (ALC1) had malonildialdehyde and lipid hydroperoxide concentrations significantly lower than those with an intake higher than 200 g/day (ALC2). These differences were not related to the extent of liver injury or to the liver derangement as assessed by Child's classification. The increase in lipid peroxidation markers in ALC cirrhotic patients was associated with a decrease in, respectively, plasma alpha-tocopherol and erythrocyte glutathione concentrations. Significant differences were also seen between ALC1 and ALC2 groups in plasma alpha-tocopherol, but not in erythrocyte glutathione concentrations. The concentrations of alpha-tocopherol and glutathione in the blood of NAC patients were in contrast not substantially different from those of healthy controls. The close association between oxidative damage and alcohol abuse suggested that free radical intermediates produced during ethanol metabolism might be responsible for causing oxidative damage.

A strong negative association between alcohol consumption and the risk of hepatocellular carcinoma in cirrhotic patients

We carried out a hospital-based, case-control study to assess the association of both the Hepatitis B Virus (HBV) infection and the lifetime daily alcohol intake with the risk of developing hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). Cases were 62 consecutive inpatients of a Gastroenterology Division in whom a first diagnosis of HCC superimposed on LC was made. Two control groups were used: 310 patients without liver disease, matched 1:5 with cases and randomly selected from inpatients of the same hospital, and 97 consecutive asymptomatic inpatients in whom the first diagnosis of LC was made. Alcohol intake was quantified in all subjects by a standardized questionnaire. HBV infection was associated with HCC development in cirrhotics (odds ratio = 6.8; 95% confidence interval = 1.4-32.3), whereas we observed a trend towards a decreased HCC risk at increased alcohol intake values (odds ratio from 1 for lifetime abstainers to 0.2 for drinkers of 175 g/day or more). Our results suggest that alcohol intake is not a direct determinant of HCC, but its role is mediated by LC. Cirrhotics with high alcohol intake do not usually survive long enough to develop HCC.

Amount and duration of alcohol intake as risk factors of symptomatic liver cirrhosis: a case—control study

We carried out a hospital based case-control study involving 320 patients with symptomatic liver cirrhosis (LC) and 320 pair-matched control individuals, in order to estimate the dose-response relationship between both the daily amount and the duration of alcohol intake and the risk of LC. Lifetime alcohol consumption was measured by a standardized and reproducible questionnaire, and expressed as lifetime daily alcohol intake (LDAI) and duration of alcohol consumption (DAC). The odds ratio (OR) for LC was estimated by the conditional logistic regression. It increased from 1.0 for lifetime abstainers to 4.2 for LDAI of 225 g or more. Comparing durations of alcohol consumption of ⩽I 0 and ⩾ 30 years in the model, the ORs consistently decreased for all the LDAI categories: from 4.1 to 0.6 in the 25–50 g category; from 15.1 to 0.9 in the 75–100 g category; from 67.2 to 1.5 in the 125 g or more category. Our results suggest that the dose-dependent relationship between alcohol and LC may be mediated by the degree of individual susceptibility to the detrimental effect of alcohol to the liver.

Interaction between alcohol consumption and positivity for antibodies to hepatitis C virus on the risk of liver cirrhosis: a case-control study. Provincial Group for the Study of Chronic Liver Disease.

To assess the risk of developing liver cirrhosis associated with alcohol consumption, HBV and HCV infection markers, we carried out a case-control study involving 115 patients admitted to the medical departments of the general hospitals in the province of L'Aquila (Abruzzo, Italy) who received for the first time the diagnosis of liver cirrhosis, and 167 controls randomly selected among patients admitted to the same hospitals as the cases. Alcohol intake was measured in all 282 subjects using an already validated standardized questionnaire, and expressed as mean lifetime daily alcohol intake in grams. The mean lifetime daily alcohol intake showed a dose-dependent effect on the risk of cirrhosis: the relative risk significantly rose to 3.8 (95% CI: 2.0-7.3) for a mean daily intake of > or = 101 g alcohol; for HBsAg positivity the relative risk of cirrhosis was 23.0 (95% CI: 4.9-107.8) and for anti-HCV positivity it was 8.7 (95% CI: 4.3-17.6). After applying a multiple logistic regression analysis in a multivariate model including mean lifetime alcohol intake and anti-HCV status, both variables were significantly associated with the risk of cirrhosis (relative risks = 5.3-95% CI: 2.3-12.2 and 9.9-95% CI: 4.4-22.0, respectively). The combination of these two variables was found to fit an additive--but not multiplicative--model relative to the risk of cirrhosis: furthermore, the interaction of the anti-HCV status with the presence or absence of cirrhosis did not result in a significant source of variability for the mean lifetime daily alcohol intake.(ABSTRACT TRUNCATED AT 250 WORDS)