Andriy V. Samokhvalov

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

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 versus morbidity where possible; and to 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 epidemiological 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 and fetal 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 linked causally to IHD, fetal 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+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. CONCLUSIONS Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol-disease relationships.

Global burden of alcoholic liver diseases

Liver diseases contribute markedly to the global burden of mortality and disease. This paper provides an overview from a global perspective of the contribution of alcohol to liver diseases. The Global Burden of Disease study methodology was used to estimate the burden of alcohol-attributable liver cirrhosis and alcohol-attributable liver cancer in 2010 as measured by deaths and disability adjusted life years (DALYs). This methodology estimates attributable fractions based on alcohol exposure distribution and relative risks associated with different levels of drinking. Globally, in 2010, alcohol-attributable liver cirrhosis was responsible for 493,300 deaths (156,900 female deaths and 336,400 male deaths) and 14,544,000 DALYs (4,112,000 DALYs for women and 10,432,000 DALYs for men), representing 0.9% (0.7% for women and 1.2% for men) of all global deaths and 0.6% (0.4% for women and 0.8% for men) of all global DALYs, and 47.9% of all liver cirrhosis deaths (46.5% for women and 48.5% for men) and 46.9% of all liver cirrhosis DALYs (44.5% for women and 47.9% for men). Alcohol-attributable liver cancer was responsible for 80,600 deaths (14,800 female deaths and 65,900 male deaths) and 2,142,000 DALYs (335,000 DALYs for women and 1,807,000 DALYs for men). The burden of alcohol-attributable liver cirrhosis and liver cancer is high and entirely preventable. Interventions to reduce alcohol consumption are recommended as a population health priority and may range from taxation increases for alcoholic beverages to increases in screening and treatment rates for alcohol use disorders.

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review.

BackgroundIn 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship.MethodsA systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken.ResultsThere is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol.ConclusionThe epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.

Alcohol Consumption as a Risk Factor for Atrial Fibrillation: a Systematic Review and Meta-Analysis

Background Alcohol exposure is one of the major risk factors for global burden of disease, but atrial fibrillation (AF) had not yet been included in these estimates. The purpose of this contribution was to examine the dose-response relationship between alcohol consumption and AF and to explore potential causal pathways. Design and methods Systematic literature review and meta-analyses. Results Overall, a consistent dose-response relationship between the amount of alcohol consumed daily and the probability of the onset of AF was found. Women consuming 24, 60 and 120 g of alcohol daily had relative risks of 1.07 [95% confidence interval (CI): 1.04–1.10], 1.42 (95% CI: 1.23–1.64) and 2.02 (95% CI: 1.60–2.97), respectively, relative to nondrinkers. Among men, the corresponding relative risks were 1.08 (95% CI: 1.04–1.11), 1.44 (95% CI: 1.23–1.69) and 2.09 (95% CI: 1.52–2.86). Based on the categorical analyses, we could not exclude the existence of a threshold (three drinks a day for men and two drinks a day for women). Several pathogenic mechanisms for the development of AF in alcohol users were identified. Conclusion Epidemiological criteria for causality were met to conclude a causal impact of alcohol consumption on the onset of AF with a monotonic dose-response relationship. However, the impact of light drinking is not clear.

A systematic review of the epidemiology of unrecorded alcohol consumption and the chemical composition of unrecorded alcohol

BACKGROUND AND AIMS Unrecorded alcohol constitutes about 30% of all alcohol consumed globally. The aims of this systematic review were to determine the epidemiology (occurrence, types, prevalence) of unrecorded alcohol consumption in different countries/regions, analyse the chemical composition of unrecorded alcohol and examine health outcomes caused by the consumption of unrecorded alcohol, based on either epidemiology or toxicology. METHODS A systematic search for, and qualitative analysis of, papers with empirical results on the different categories of unrecorded alcohol, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS Unrecorded alcohol was widespread in all regions of the world. Artisanal fermented beverages and spirits were the most common categories of unrecorded alcohol globally, and were available on all continents. In India, industrially produced spirits (country spirits) were most prevalent. In Russia and countries of the former Soviet Union, surrogate alcohols complemented artisanal spirits. Cross-border shopping was the most prevalent method of obtaining unrecorded alcohol in parts of Europe. Ethanol was the most harmful ingredient of unrecorded alcohol, and health consequences due to other ingredients found in unrecorded alcohol were scarce. However, as unrecorded alcohol is usually the least expensive form of alcohol available in many countries, it may contribute to higher rates of chronic and irregular heavy drinking. CONCLUSIONS Very large amounts of alcohol are produced globally that go unrecorded. The primary harm from this kind of alcohol arises from the fact that it is typically much cheaper than licit alcohol.

Alcohol consumption, unprovoked seizures, and epilepsy: a systematic review and meta-analysis.

Purpose:  The purpose of this research was to analyze and quantify the association between alcohol consumption and epilepsy as an independent disease, in part operationalized by the occurrence of unprovoked seizures, as well as to examine causality.

The relationship between different dimensions of alcohol use and the burden of disease-an update.

Abstract Background and aims Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs). Methods Systematic review of reviews and meta‐analyses on alcohol consumption and health outcomes attributable to alcohol use. For dimensions of exposure: volume of alcohol use, blood alcohol concentration and patterns of drinking, in particular heavy drinking occasions were studied. For liver cirrhosis, quality of alcohol was additionally considered. For all outcomes (mortality and/or morbidity): cause of death and disease/injury categories based on International Classification of Diseases (ICD) codes used in global CRAs; harm to others. Results In total, 255 reviews and meta‐analyses were identified. Alcohol use was found to be linked causally to many disease and injury categories, with more than 40 ICD‐10 three‐digit categories being fully attributable to alcohol. Most partially attributable disease categories showed monotonic relationships with volume of alcohol use: the more alcohol consumed, the higher the risk of disease or death. Exceptions were ischaemic diseases and diabetes, with curvilinear relationships, and with beneficial effects of light to moderate drinking in people without heavy irregular drinking occasions. Biological pathways suggest an impact of heavy drinking occasions on additional diseases; however, the lack of medical epidemiological studies measuring this dimension of alcohol use precluded an in‐depth analysis. For injuries, except suicide, blood alcohol concentration was the most important dimension of alcohol use. Alcohol use caused marked harm to others, which has not yet been researched sufficiently. Conclusions Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered. Epidemiological studies should include measurement of heavy drinking occasions in line with biological knowledge.

Alcohol consumption as a risk factor for pneumonia: a systematic review and meta-analysis.

The aim of this study was to quantify the association between alcohol consumption and incidence of pneumonia and to examine possible pathways. This was done by a systematic review and meta-analyses on the dose-response relationship between alcohol consumption or alcohol-use disorders and the incidence of community-acquired pneumonia (CAP). The relative risk (RR) of CAP increased monotonically with increasing alcohol consumption. Individuals consuming 24, 60, and 120 g of pure alcohol daily demonstrated RRs for incident CAP of 1·12 (95% CI 1·02-1·23), 1·33 (95% CI 1·06-1·67) and 1·76 (95% CI 1·13-2·77), respectively, relative to non-drinkers. Clinically defined alcohol-use disorders were associated with an eightfold increased risk of CAP (RR 8·22, 95% CI 4·85-13·95). In conclusion, alcohol was found to be a risk factor for pneumonia with a clear statistical association, and a monotonic dose-response relationship.

Unrecorded alcohol consumption in Russia: toxic denaturants and disinfectants pose additional risks

Unrecorded alcohol consumption in Russia: toxic denaturants and disinfectants pose additional risks In 2005, 30% of all alcohol consumption in Russia was unrecorded. This paper describes the chemical composition of unrecorded and low cost alcohol, including a toxicological evaluation. Alcohol products (n=22) from both recorded and unrecorded sources were obtained from three Russian cities (Saratov, Lipetsk and Irkutsk) and were chemically analyzed. Unrecorded alcohols included homemade samogons, medicinal alcohols and surrogate alcohols. Analysis included alcoholic strength, levels of volatile compounds (methanol, acetaldehyde, higher alcohols), ethyl carbamate, diethyl phthalate (DEP) and polyhexamethyleneguanidine hydrochloride (PHMG). Single samples showed contamination with DEP (275-1269 mg/l) and PHMG (515 mg/l) above levels of toxicological concern. Our detailed chemical analysis of Russian alcohols showed that the composition of vodka, samogon and medicinal alcohols generally did not raise major public health concerns other than for ethanol. It was shown, however, that concentration levels of DEP and PHMG in some surrogate alcohols make these samples unfit for human consumption as even moderate drinking would exceed acceptable daily intakes.

Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses.

Background Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. Methods We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose–response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. Findings Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose–response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60–0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69–1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04–13.02). Interpretation The dose–response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. Funding The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author.