Gro Askgaard

Alcohol drinking pattern and risk of alcoholic liver cirrhosis: A prospective cohort study

BACKGROUND & AIMS Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. RESULTS We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50-59 years) was associated with an increased risk, whereas the amount in 20-29 and 30-39 years was not. In men drinking 14-28 drinks/week, HR was 7.47 (95% CI: 1.68; 33.12), 3.12 (95% CI: 1.53; 6.39), and 1.69 (95% CI: 0.79; 3.65) in drinkers of little (<1% of weekly amount), some (1-15%), and mostly wine (50-100%), compared to drinking <14 drinks/week. In general, results were similar for women. CONCLUSIONS In men, daily drinking was associated with an increased risk of alcoholic cirrhosis. Recent alcohol consumption rather than earlier in life was associated with risk of alcoholic cirrhosis. Compared to beer and liquor, wine might be associated with a lower risk of alcoholic cirrhosis.

Predictors of Health-Related Quality of Life in Outpatients with Cirrhosis: Results from a Prospective Cohort

Background. Cirrhosis may lead to a poor health-related quality of life (HRQOL), which should be taken into consideration when addressing the cirrhotic outpatient. Methods. Prospective cohort study evaluating predictors of HRQOL in outpatients with cirrhosis. Patients with overt hepatic encephalopathy at baseline were excluded. HRQOL was evaluated at baseline using the six point Chronic Liver Disease Questionnaire. Predictors of low quality of life scores (<4 points) and mortality were analyzed using multivariable logistic regression. Results. In total, 92 patients were included (mean age 61 years, 59% male). Nineteen patients died (mean duration of follow-up 20 months). The mean Child-Pugh score was 6.9. Twenty percent had a poor HRQOL judged by the Chronic Liver Disease Questionnaire score and 45% had covert hepatic encephalopathy. The only predictors of poor HRQOL were the Child-Pugh score (β=0.45;P = 0.013), nonalcoholic etiology of cirrhosis (β=−2.34;P = 0.009), and body mass index (β=−0.20;P = 0.023). The body mass index predicted poor HRQOL independently of the presence of ascites and albumin level. Conclusions. The body mass index was associated with a low HRQOL. This suggests that malnutrition may be an important target in the management of patients with cirrhosis.

Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems: A nationwide prospective cohort study

Alcoholic liver cirrhosis is usually preceded by many years of heavy drinking, in which cessation in drinking could prevent the disease. Alcohol problems are not consistently managed in hospital patients. We followed all Danish patients with an initial hospital contact with alcohol problems (intoxication, harmful use, or dependence) during 1998‐2002 for alcoholic liver cirrhosis development (n = 36,044). In this registry‐based cohort, we identified predictors of the absolute risk for alcoholic liver cirrhosis. Incidence rate ratios (IRRs) were estimated as the incidence rate of alcoholic liver cirrhosis in these patients relative to the general population. Age and alcohol diagnosis were significant predictors of alcoholic liver cirrhosis risk in men and women, whereas civil status, education, and type of hospital care were not. In men, the 15‐year absolute risk was 0.7% (95% confidence interval [CI], 0.4, 0.8) for 20‐29 years, 5.5% (95% CI, 4.9, 6.2) for 30‐39 years, 9.8% (95% CI, 9.0, 11) for 40‐49 years, 8.9% (95% CI, 8.1, 9.8) for 50‐59 years, 6.2% (95% CI, 5.1, 7.2) for 60‐69 years, and 2.5% (95% CI, 1.7, 3.3) for 70‐84 years. According to alcohol diagnosis in men, the 15‐year absolute risk was 2.6% (95% CI, 2.3, 2.9) for intoxication, 7.7% (95% CI, 6.4, 7.9) for harmful use, and 8.8% (95% CI, 8.2, 9.4) for dependence. The IRR for alcoholic liver cirrhosis in the cohort relative to the general population was 11 (95% CI, 10, 12) in men and 18 (95% CI, 15, 21) in women. Conclusion: Hospital patients with alcohol problems had a much greater risk for alcoholic liver cirrhosis compared to the general population. The risk was particularly increased for patients 40‐59 years and for patients diagnosed with harmful use or dependence. (Hepatology 2017;65:929‐937).

Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality

BACKGROUND Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS The study was a register-based cohort study of patients admitted for alcohol withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS A total of 1063 patients treated with chlordiazepoxide and 1365 patients treated with phenobarbital were included. After one year, the outcome rates per 100 person-years in the phenobarbital versus the chlordiazepoxide cohort were 9.20 vs. 5.13 for use of benzodiazepine, 37.9 vs. 37.9 for alcohol recidivism and 29 vs. 59 for mortality. Comparing phenobarbital to chlordiazepoxide treated, the HR of subsequent use of benzodiazepines was 1.56 (95%CI 1.05-2.30). Similarly, the HR for alcohol recidivism was 0.99 (95%CI 0.84-1.16). Lastly, the HR for 30-days and 1 year mortality was 0.25 (95%CI 0.08-0.78) and 0.51 (95%CI 0.31-0.86). CONCLUSION There was no decreased risk of subsequent benzodiazepine use or alcohol recidivism in patients treated with phenobarbital compared to chlordiazepoxide. Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide.

Use of disulfiram and risk of cancer: a population-based case-control study.

Experimental studies have indicated that disulfiram (Antabuse) has antineoplastic effects against melanoma, breast, and prostate cancer. To explore this hypothesis, we examined the association between disulfiram use and these cancers in a nationwide register-based case–control study nested within ever-users (≥one prescription) of disulfiram. Cases were all Danish individuals with a histologically verified first-time diagnosis of malignant melanoma, breast, or prostate cancer during 2000–2009. For each case, we selected four cancer-free controls matched for age, sex, and year of first disulfiram prescription using risk set sampling. Similarly, for secondary analyses, we selected case–control populations for selected tobacco-related and alcohol-related cancer types, that is, cancers of the buccal cavity, liver, lung, and colorectal cancer. Disulfiram use 1 year before cancer diagnosis and the corresponding date for controls were disregarded. We estimated crude and adjusted odds ratios and 95% confidence intervals (CI) for cancer associated with long-term (≥500 daily defined doses) versus one-time (one prescription) use of disulfiram. Among 53 856 disulfiram users, we identified 166, 644, and 464 cases, respectively, of melanoma, breast, or prostate cancer. Adjusted odds ratios for melanoma, breast, or prostate cancer associated with long-term disulfiram use were 1.04 (95% CI: 0.60–1.78), 0.92 (95% CI: 0.70–1.22), and 0.77 (95% CI: 0.56–1.06), respectively. For prostate cancer, dose–response analyses showed a further risk reduction with the highest cumulative dose level of disulfiram; however, the test for trend did not reach statistical significance. Our study provides some epidemiological support for a protective effect of disulfiram against prostate and breast cancer.

Predictors of heavy drinking after liver transplantation for alcoholic liver disease in Denmark (1990–2013): a nationwide study with competing risks analyses

Abstract Objective. Heavy drinking following liver transplantation decreases survival. Little is known of predictors of heavy drinking, which should guide clinicians identifying patients at high risk of return to heavy drinking after transplantation. Material and methods. We calculated the cumulative incidence of heavy drinking among patients transplanted for alcoholic liver disease in Denmark 1990–2013. We then analyzed pre-transplant demographic and psychiatric characteristics as predictors of post-transplant heavy drinking. Information was obtained from medical records, from nationwide registries and by interview. Results. Among 156 liver-transplanted patients, the cumulative incidence of heavy drinking was 18%, 24% and 27% after 5, 10 and 15 years post-transplant. In univariate analyses of pre-transplant predictors of heavy drinking after transplantation, younger age (p < 0.001), being retired (p = 0.007), anxiety (p = 0.04), personality disorder (p = 0.05) and no lifetime diagnosis of alcohol dependence (p = 0.03) were associated with heavy drinking after transplantation. Smoking (p = 0.06) tended to be associated, whereas depression (p = 0.7) or being married was not (p = 0.7). In the multivariate analysis, only younger age (p = 0.03), being retired (p = 0.007) and no lifetime diagnosis of alcohol dependence (p = 0.003) remained significant predictors. Heavy drinking after transplantation decreased survival beyond 5 years post-transplant (p = 0.004). Conclusions.There is a high incidence of heavy drinking after liver transplantation for alcoholic cirrhosis in Denmark. Younger age, being retired and no lifetime diagnosis of alcohol dependence were predictors of heavy drinking after transplantation.

Hospital contacts with alcohol problems prior to liver cirrhosis or pancreatitis diagnosis

AIM To evaluate prior hospital contacts with alcohol problems in patients with alcoholic liver cirrhosis and pancreatitis. METHODS This was a register-based study of all patients diagnosed with alcoholic liver cirrhosis or pancreatitis during 2008-2012 in Denmark. Hospital contacts with alcohol problems (intoxication, harmful use, or dependence) in the 10-year period preceding the diagnosis of alcoholic liver cirrhosis and pancreatitis were identified. RESULTS In the 10 years prior to diagnosis, 40% of the 7719 alcoholic liver cirrhosis patients and 40% of the 1811 alcoholic pancreatitis patients had at least one prior hospital contact with alcohol problems. Every sixth patient (15%-16%) had more than five contacts. A similar pattern of prior hospital contacts was observed for alcoholic liver cirrhosis and pancreatitis. Around 30% were diagnosed with alcohol dependence and 10% with less severe alcohol diagnoses. For the majority, admission to somatic wards was the most common type of hospital care with alcohol problems. Most had their first contact with alcohol problems more than five years prior to diagnosis. CONCLUSION There may be opportunities to reach some of the patients who later develop alcoholic liver cirrhosis or pancreatitis with preventive interventions in the hospital setting.

Opportunities to Prevent Alcoholic Liver Cirrhosis in High-risk Populations: A Systematic Review With Meta-analysis

BACKGROUND: Alcoholic liver cirrhosis is preventable and caused by heavy drinking. Few in the general population may be at risk and interventions targeting individuals at high risk may be a more feasible opportunity for prevention than interventions targeting the whole population. METHODS: We conducted a systematic review to identify opportunities to prevent alcoholic liver cirrhosis in high-risk populations. Following MOOSE guidelines, we included observational studies published between 1980 and 2017. Prospective studies of alcohol-problem cohorts were included to investigate whether alcohol-problem cohorts qualify as high-risk populations for alcoholic liver cirrhosis. Studies on the alcohol amount consumed by alcoholic liver cirrhosis patients were included to compare with the amount consumed by the general population. Moreover, studies on alcohol-related healthcare contacts prior to alcoholic liver cirrhosis diagnosis were included to identify opportunities to offer prevention interventions. Of 7198 screened references, 38 studies (N = 120,928) were included. RESULTS: Alcohol-problem cohorts qualified as high-risk populations with an incidence of alcoholic liver cirrhosis ranging from 7 to 16% after 8–12 years. The alcohol amount consumed by alcoholic liver cirrhosis patients was high compared to the general population. For example, 45% (95%CI 34, 56) of alcoholic liver cirrhosis patients were drinking >110 g alcohol/day. Finally, there were opportunities to reach alcoholic liver cirrhosis patients prior to diagnosis; 40–61% of alcoholic liver cirrhosis patients had a previous alcohol-related healthcare contact. CONCLUSIONS: We conclude that alcohol-problem cohorts are high-risk populations for alcoholic liver cirrhosis and there seems to be opportunities to reach later alcoholic liver cirrhosis cases with preventive interventions in healthcare settings.Alcoholic liver cirrhosis is preventable and caused by heavy drinking. Few in the general population may be at risk and interventions targeting individuals at high risk may be a more feasible opportunity for prevention than interventions targeting the whole population. We conducted a systematic review to identify opportunities to prevent alcoholic liver cirrhosis in high-risk populations. Following MOOSE guidelines, we included observational studies published between 1980 and 2017. Prospective studies of alcohol-problem cohorts were included to investigate whether alcohol-problem cohorts qualify as high-risk populations for alcoholic liver cirrhosis. Studies on the alcohol amount consumed by alcoholic liver cirrhosis patients were included to compare with the amount consumed by the general population. Moreover, studies on alcohol-related healthcare contacts prior to alcoholic liver cirrhosis diagnosis were included to identify opportunities to offer prevention interventions. Of 7198 screened references, 38 studies (N = 120,928) were included. Alcohol-problem cohorts qualified as high-risk populations with an incidence of alcoholic liver cirrhosis ranging from 7 to 16% after 8–12 years. The alcohol amount consumed by alcoholic liver cirrhosis patients was high compared to the general population. For example, 45% (95%CI 34, 56) of alcoholic liver cirrhosis patients were drinking >110 g alcohol/day. Finally, there were opportunities to reach alcoholic liver cirrhosis patients prior to diagnosis; 40–61% of alcoholic liver cirrhosis patients had a previous alcohol-related healthcare contact. We conclude that alcohol-problem cohorts are high-risk populations for alcoholic liver cirrhosis and there seems to be opportunities to reach later alcoholic liver cirrhosis cases with preventive interventions in healthcare settings.

Number of hospital contacts with alcohol problems predicts later risk of alcoholic liver cirrhosis.

Aims: Alcoholic liver cirrhosis is usually preceded by years of heavy drinking. We investigated whether the risk of alcoholic liver cirrhosis increases as the number of hospital contacts with alcohol problems goes up. Methods: This was a supplementary analysis on a nationwide register-based cohort study. All patients in Denmark with an initial hospital contact with alcohol problems (alcohol intoxication, harmful alcohol use or alcohol dependence) 1998–2002, free of liver disease, were followed for diagnosis of alcoholic liver cirrhosis. The number of subsequent hospital contacts with alcohol problems was estimated as a time-dependent variable for each patient. Results: In all, 36,044 hospital patients with an initial hospital contact with alcohol problems were included. These patients had 301,525 subsequent hospital contacts with alcohol problems. Risk of alcoholic liver cirrhosis increased (p < 0.0001) with number of alcohol hospital contacts in both men and women for up to nine contacts. Conclusions: The number of prior hospital contacts with alcohol problems might provide clinicians with a helpful metric in deciding whether to offer preventive interventions for alcoholic liver cirrhosis.