The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol.
We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), ?-glutamyl-transferase (?-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56).
In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic-IV analyses] and ?-GT [8.2% (7.8, 8.5) and 6.8% (-2.8, 16.5)]. The point estimates from the two methods were very similar and statistically the results from the two methods were consistent with each other for effects with ALT and ?-GT (both pdiff>0.3). Results from the multivariable analyses suggested a weak inverse association of alcohol with ALP [-1.5% (-1 .7, -1.3)], which differed from the strong positive effect found in genetic-IV analyses [11.6% (6.8, 16.4)] (p diff
BACKGROUND: Based on the increased consumption of alcohol in Denmark the aim of this study was to measure prevalence of abnormal liver-derived enzymes in a homogeneous Danish population and possible associations with alcohol consumption, smoking and body mass index (BMI). METHOD: In a representative population sample of 905 people (aged 30-50) from the baseline survey of the Ebeltoft Health Promotion Project in Denmark, we examined prevalence of abnormal liver-derived enzymes and its possible association with self-reported alcohol consumption, smoking and BMI, applying logistic regression analyses. RESULTS: In a significant proportion, 12% (women 8%; men 16%) of the cohort we found raised levels of liver-derived enzymes associated with moderate self-reported alcohol intake adjusted for BMI and smoking. If the intake was higher than moderate, i.e. > 28 units per week (one unit equals 12 g of alcohol), the odds ratio (OR) for raised liver enzymes increased further; S-gamma-glutamyltransferase (GGT) (OR: for women 24.4; men 18.4). S-aspartate-aminotransferase (ASAT) (24.2; 5.8) and S-alanine-aminotransferase (ALAT) (27.2; 3.0). Furthermore, daily smoking increased the risk of raised liver enzymes in women (OR: 3.4-4.2), and obesity (BMI > or = 30 kg/m2) in men showed a positive association with all three enzymes (OR: 3.0-9.0). CONCLUSIONS: The occurrence of raised liver-derived enzymes was frequent in the Danish population sample and associated with moderate self-reported alcohol consumption adjusted for BMI and smoking.
Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern.
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.
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 (
Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients with alcoholic cirrhosis vs controls in Denmark.
We collected data from nationwide health care registries to identify and follow up all citizens of Denmark diagnosed with alcoholic cirrhosis from 1977 through 2010. Each patient was matched with 5 random individuals from the population (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination).
Of the 24,679 patients diagnosed with alcoholic cirrhosis, 532 developed an autoimmune disease, yielding an overall increased adjusted incidence rate ratio (aIRR) of 1.36 (95% confidence interval [CI], 1.24-1.50). The strongest associations were with Addison's disease (aIRR, 2.47; 95% CI, 1.04-5.85), inflammatory bowel disease (aIRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate for polymyalgia rheumatica decreased in patients with alcoholic cirrhosis compared with controls (aIRR, 0.47; 95% CI, 0.33-0.67).
Based on a nationwide cohort study of patients in Denmark, alcoholic cirrhosis is a risk factor for several autoimmune diseases.
BACKGROUND: Denmark has one of the highest alcohol consumption rates in Northern Europe. The overall per capita alcohol consumption has been stable in recent decades, but surveys have indicated that consumption has decreased in the young and increased in the old. However, there is no recent information on the epidemiology of alcoholic cirrhosis. We examined time trends in incidence, prevalence, and hospitalization rates of alcoholic cirrhosis in Denmark between 1988 and 2005. METHODS: We used data from a nationwide population-based hospital registry to identify all Danish citizens with a hospital diagnosis of alcoholic cirrhosis. We computed standardized incidence rates, prevalence and hospitalization rates of alcoholic cirrhosis within the Danish population. We also computed the number of hospitalizations per alcoholic cirrhosis patient per year. RESULTS: From 1988 to 1993, incidence rates for men and women of any age showed no clear trend, and after a 32 percent increase in 1994, rates were stable throughout 2005. In 2001-2005, the incidence rates were 265 and 118 per 1,000,000 per year for men and women, respectively, and the prevalence rates were 1,326 and 701 per 1,000,000. From 1994, incidence, prevalence, and hospitalization rates decreased for men and women younger than 45 years and increased in the older population, although the latter finding might be partly explained by changes in coding practice. Men and women born around 1960 or later had progressively lower age-specific alcoholic cirrhosis incidence rates than the generations before them. From 1996 to 2005, the number of hospitalizations per alcoholic cirrhosis patient per year increased from 1.3 to 1.5 for men and from 1.1 to 1.2 for women. CONCLUSION: From 1988 to 2005, alcoholic cirrhosis put an increasing burden on the Danish healthcare system. However, the decreasing incidence rate in the population younger than 45 years from 1994 indicated that men and women born around 1960 or later had progressively lower incidence rates than the generations before them. Therefore, we expect the overall incidence and prevalence rates of alcoholic cirrhosis to decrease in the future.
Tobacco smoke exposure increases the risk of cancer in the liver, but little is known about the possible risk associated with exposure to ambient air pollution.
We evaluated the association between residential exposure to air pollution and primary liver cancer incidence.
We obtained data from four cohorts with enrolment during 1985-2005 in Denmark, Austria and Italy. Exposure to nitrogen oxides (NO2 and NOX), particulate matter (PM) with diameter of less than 10µm (PM10), less than 2.5µm (PM2.5), between 2.5 and 10µm (PM2.5-10) and PM2.5 absorbance (soot) at baseline home addresses were estimated using land-use regression models from the ESCAPE project. We also investigated traffic density on the nearest road. We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and random-effects meta-analyses to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs).
Out of 174,770 included participants, 279 liver cancer cases were diagnosed during a mean follow-up of 17 years. In each cohort, HRs above one were observed for all exposures with exception of PM2.5 absorbance and traffic density. In the meta-analysis, all exposures were associated with elevated HRs, but none of the associations reached statistical significance. The summary HR associated with a 10-µg/m(3) increase in NO2 was 1.10 (95% confidence interval (CI): 0.93, 1.30) and 1.34 (95% CI: 0.76, 2.35) for a 5-µg/m(3) increase in PM2.5.
The results provide suggestive evidence that ambient air pollution may increase the risk of liver cancer. Confidence intervals for associations with NO2 and NOX were narrower than for the other exposures.
HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc less than 0.001); B7: 33.1% vs. 15.6% (Pc less than 0.001); B14: 6.9% vs. 3.0% (Pc greater than 0.05); B38: 5% vs. 0.9% (Pc greater than 0.05); B47: 4.0% vs. 0.4% (Pc greater than 0.05). Pedigree analyses disclosed 19 different haplotypes in IH subjects, compared to 286 haplotypes in controls. The following haplotypes occurred with higher frequency in IH compared to controls: A3,B5: 10.3% vs. 0.3% (Pc less than 0.001); A3,B7: 25.6% vs. 6.6% (Pc = 0.001); A3,B14: 3.4% vs. 0.6% (Pc greater than 0.05); A3,B47: 6.9% vs. 0.2% (Pc greater than 0.05). The major IH marker HLA-A3 was found in 56% of the haplotypes. The patterns of HLA-alleles associated with IH in Denmark show similarities to those in Central Europe, Australia, USA and Canada, being A3,B7 dominated and those in Central Sweden, England and Ireland, being A3,B14 dominated.
Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early treatment strategies on the course of disease.
A population-based cohort of patients from January 1993 to September 2009 was identified prospectively, and the patient data were collected by a retrospective examination of the files.
Twenty-nine patients had type 1 AIH, 2 had type 2, and 2 could not be categorised. Among the 33 children, 16 (48.5%) were girls and 17 (51.5%) were boys. Twenty-three (69.7%) of the patients had symptoms at presentation indistinguishable from acute viral hepatitis, but in 16 (69.6%) of those the liver biopsy showed cirrhosis. Twenty (60.6%) patients were treated with prednisolone and azathioprine at the time of remission, whereas 8 (24.2%) were treated with prednisolone. One (3%) patient did not experience remission during the observation period.
The patients in our study appeared similar to previously published cohorts, although a female predominance was not observed. Our data suggest that early treatment including both prednisolone and azathioprine could be more effective than prednisolone alone, even if randomised controlled paediatric studies comparing these 2 different treatment regimens are needed.