Alcohol Consumption: Medical Implications, the Liver and Beyond

Abstract

Alcohol consumption represents a major factor of morbidity and mortality, with a wide range of adverse medical implications that practically affect every organ system. It is the fifth major cause of deaths in men and women and causes up to 139 million disability-adjusted life years. Solid evidence places the risk as undoubtedly correlated to the length of time and amount of alcohol consumption. While alcohol-related liver disease represents one of the most studied and well-known consequences of alcohol use, the term itself embodies a wide spectrum of progressive disease stages that are responsible for almost half of the liver-related mortality worldwide. We discuss the staged alcohol-related fatty liver, alcohol-related steatohepatitis and, finally, fibrosis and cirrhosis, which ultimately may end up in a hepatocellular carcinoma. Other comorbidities such as acute and chronic pancreatitis; central nervous system; cardiovascular, respiratory and endocrine system; renal disease; urological pathologies; type 2 diabetes mellitus and even infectious diseases are reviewed in their relation to alcohol consumption. This article reviews the impact of alcohol use on different systems and organs, summarizing available evidence regarding its medical implications. It examines current basic and clinical data regarding mechanisms to highlight factors and processes that may be targetable to improve patient outcomes. Although alcohol use is a part of many cultural and social practices, as healthcare providers we must identify populations at high risk of alcohol abuse, educate patients about the potential alcohol-related harm and provide appropriate treatment.

INTRODUCTION

Alcohol use represents one of the five major morbimortality factors worldwide and accounts for 5.1% of the total global disease burden. It causes 7.6% of deaths in men and 4.0% among women, and 139 million disability-adjusted life years (DALYs) are attributable to its intake. Nearly 43% of adults globally have consumed alcohol in 2019, and it has been estimated that the average drinking quantity of individuals above 15 years surpasses the 6.4 l mark (Arab et al., 2019; World Health Organization, 2019). The consumption of alcohol is associated with a wide range of adverse medical implications that practically affect every system of the body. In addition, alcohol consumption has been associated with multiple cancers (Table 1), which may be explained by acetaldehyde’s genotoxic effect, production of reactive oxygen and nitrogen species, changes in folate metabolism and DNA methylation, nutritional deficiencies, impaired immune surveillance and increased estrogen concentrations (Boffetta and Hashibe, 2006). Furthermore, alcohol may act as a solvent for tobacco carcinogens, which may partially explain their synergistic effects on certain types of cancers (Table 1).

Given that most of these effects appear to be dose-related (Table 2), efforts in the past few years have focused on standardizing types and patterns of use, so studies and conclusions about its consequences can be made. According to the National Center for Health Statistics, light alcohol use represents an intake of ≤3 drinks per week; moderate use a consumption of 4–7 drinks per week for women or 4–14 drinks per week for men; and heavy use an ingestion of >7 drinks per week for women or >14 drinks per week for men, on average over the past year. Nevertheless, conflicting information about the global definition of a standard drink (SD) still remains. The American Dietary Guidelines have established it as 14 g of pure alcohol, a quantity equivalent to 45–50 ml of liquor and 150 ml of wine or 350 ml of beer. However, in the UK and Japan, it represents different quantities, respectively, including 8 and 19 g of pure alcohol.

Alcohol use disorder (AUD), as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is a highly disabling and often overlooked condition. In the USA, an AUD lifetime prevalence of 29.1% has been estimated, leading to adverse health and social repercussions for both the individual and society (Grant et al., 2015). Binge drinking (BD), as defined by the National Institute on Alcohol Abuse and Alcoholism, is a pattern of alcohol consumption that brings blood alcohol concentration to ≥0.08 g/dl, which typically occurs following the intake of ≥5 SD by men and ≥4 SD by women over a period of approximately 2 h. BD roughly affects 24% of Americans aged 12 or older (Llerena et al., 2015) and increases the risk of many diseases by itself (Table 3).

This article reviews the impact of alcohol use on different systems and organs, summarizing available evidence regarding its medical implications.

GASTROINTESTINAL DISORDERS

The use of alcohol leads to multiple diseases of the gastrointestinal tract. Alcohol-related liver disease (ALD) represents one of the most studied and well-known consequences of alcohol use, and the term embodies a wide spectrum of progressive disease stages that are responsible for almost half of the liver-related mortality worldwide (Rehm et al., 2013). The first of these stages is known as alcohol-associated fatty liver (AFL), a phase characterized by steatosis. Although most chronic heavy drinkers (90–100%) develop AFL, only 10–20% of them progress to an ulterior ALD stage, with additional risk factors such as genetics, sex and increased consumption being involved. When the disease continues its natural course, hepatic inflammation, hepatocyte injury and ballooning appear, reaching the stage recognized as alcoholic steatohepatitis. Finally, it leads to fibrosis and cirrhosis, which ultimately may end up in hepatocellular carcinoma (HCC).

Chronic alcohol use may also prompt the appearance of alcoholic foamy degeneration (AFD), a condition characterized by diffuse microvesicular steatosis. AFD appears to be caused by alcohol-induced mitochondrial DNA damage, and it may present with jaundice, hepatomegaly or hepatic decompensation, mimicking the presentation of alcoholic hepatitis.

Alcohol-associated cirrhosis (AC) represents up to 50% of the overall cirrhosis burden worldwide (Arab et al., 2019), and in 2010 was responsible for 493,300 deaths and 14,544,000 DALYs, which accounts for 0.9% of all global deaths and 0.6% of all global DALYs (Rehm et al., 2013). In the USA, alcohol consumption and AC prevalence have increased, an element of importance given that this type of cirrhosis duplicates the healthcare costs, causes more readmissions and tends to be associated with a worse presentation than any other non-alcohol-related cirrhosis (Mellinger et al., 2018).

Several studies have correlated heavy alcohol consumption with an increased risk of liver cirrhosis, and its risk is undoubtedly correlated to the length of time of alcohol consumption, as chronic use triggers sequential mechanisms such as lipid droplet accumulation within hepatocytes, inflammatory injury, fibrogenesis and ultimately carcinogenesis (Arab et al., 2019). A meta-analysis showed that a one drink/day consumption increased the risk of cirrhosis in women, but not in men, whereas intakes of 5–6 drinks/day heightened the risk by 12-fold in women and by almost 4-fold in men, with a dose–response relationship (Roerecke et al., 2019). Therefore, consistent evidence supports the aforementioned association. However, it must be noted that when the abstinence is achieved frequently there is an improvement in liver function, as studies have shown that alcohol abstinence may reduce portal hypertensive complications and mortality even in advanced stages of AC (Xie et al., 2014).

HCC represents more than 80% of primary liver cancers, is estimated to be the sixth most frequent cancer worldwide, and the fourth most common cause of neoplasm-related death (Burden et al., 2017). In both North America and Europe, alcohol use remains one of the biggest risk factors for its development alongside hepatitis C virus infection. In 2014, a meta-analysis by the World Cancer Research Fund found that the risk of developing HCC tended to increase by 4% per each 10 g of alcohol use in a day (World Cancer Research Fund, AIfCR, 2018).

The association between alcohol intake and pancreatic diseases is clearly documented. Alcohol use is the most common cause of chronic pancreatitis and is the second-most common etiology of acute pancreatitis, after gallstones. It is believed that the damage exerted by the alcohol on the pancreas is caused by direct toxicity to the pancreatic cells and oxidative stress induced by ethanol metabolites, all acting synergically. Recent studies have shown an exponential dose–response relationship between the average volume of alcohol intake and pancreatitis, with a proposed threshold of 4 drinks daily (Irving et al., 2009).

On the other hand, the relationship between gastroesophageal reflux disease (GERD) and alcohol has been inconsistent in the last few decades. In 2019, a meta-analysis found a solid association between alcohol drinking and the risk of developing GERD, with a pooled odds ratio (OR) of 1.48 (95% confidence interval (CI): 1.31–1.67; I₂ = 88.8%) when comparing drinkers with occasional/non-drinkers. At the same time, a linear dose–response association was described (Pan et al., 2019). This is thought to be caused by the ability of alcohol to reduce the lower esophageal sphincter pressure, impair esophageal motility and simultaneously cause a direct toxic and inflammatory effect to its mucosa. Additionally, alcohol may contribute to the development of a ‘hypercontractile esophagus’ (an abnormality of esophageal motility) and acutely inhibit gastric emptying (Grad et al., 2016), increasing the overall risk of GERD. In the same sense, the association with peptic ulcers is weak. Only one study has reported a significant relationship between chronic alcohol intake and duodenal ulcers incidence, showing a 3.3-fold increased risk with a consumption of 60 g of ethanol daily (Piper et al., 1984).

Alcohol use seems to decrease the overall risk of gallstones by increasing high-density lipoprotein (HDL)-cholesterol levels and reducing bile cholesterol saturation. In 2017, a meta-analysis showed a linear 12% risk reduction with each 10 g/day increment of alcohol use (relative risk (RR) = 0.88; 95% CI: 0.84–0.92) (Wang et al., 2017), and in 2019 another dose–response meta-analysis demonstrated a non-linear 16% risk reduction (RR = 0.84; 95% CI: 0.79–0.89; P = 0.02) (Cha et al., 2019). However, although evidence suggests a protective role, the increased prevalence of gallstones in patients with AC may be associated with an increased risk in heavy drinkers, a relation that should be further investigated (Fig. 1).

There is conflicting evidence on the relation between alcohol use and both irritable bowel syndrome (IBS) and inflammatory bowel disease. Nonetheless, alcohol use appears to worsen gastrointestinal symptoms in both conditions, which may be explained by the increase in intestinal permeability and antigen exposure, the high sugar content of alcoholic beverages that may prompt osmotic diarrhea and the development of intestinal dysbiosis (Swanson et al., 2010; Reding et al., 2013). Regarding diverticulosis and diverticular bleeding, studies have shown inconsistent findings. However, it has been suggested that alcohol may increase intracolonic pressure by impairing its motility and irritating its mucosa. Thus, a physiopathological link may still exist between these conditions (Jaruvongvanich et al., 2017). As for colorectal polyps, alcohol intake only appears to increase the risk of serrated polyps (Wang et al., 2015a).

CENTRAL NERVOUS DISORDERS

Chronic alcohol use is associated with both structural and functional brain abnormalities, which are thought to be caused by alcohol neurotoxicity, thiamine deficiency and metabolic disruption and may only be partially reversible with abstinence. A systematic review using neuroimaging techniques demonstrated that alcohol consumption may reduce the volume of gray (GM) and white matter (WM), alter WM tracts and create an imbalance of neurotransmitter systems. At the same time, studies with functional magnetic resonance imaging have shown an increased reactivity of the mesocorticolimbic system to alcohol-associated stimuli in drinkers, which may predispose them to alcohol addiction (Buhler and Mann, 2011). Similarly, a 2015 meta-analysis of nine voxel-based morphometry studies found consistent regional GM atrophy in alcohol dependence-associated areas such as the prefrontal cortex (including the anterior cingulate cortex), the dorsal striatum/insula and the posterior cingulate cortex. Comparable findings have been seen in adolescents, a group with an increased risk of damage given the high rates of alcohol consumption and the still-developing brain, which may lead to cognitive and functional consequences during adulthood (Xiao et al., 2015).

In adults with chronic alcohol intake, another neurological manifestation is alcohol-related seizures. It may be caused by different mechanisms, such as alcohol-induced stroke, trauma, vascular lesions and metabolic derangements (hypoglycemia, hyponatremia), as well as alcohol-withdrawal seizures. Alcohol use may also reduce the effectiveness of antiepileptic drugs through liver enzyme induction, which could aggravate an already diagnosed epilepsy. Data suggest that 20–40% of the patients that present to the emergency department because of a seizure have an alcohol-related one and that there is a 3-fold increase in epilepsy prevalence among alcohol-dependent patients when compared to the general population (Hillbom et al., 2003). In 2010, a meta-analysis found a solid association between alcohol consumption and epilepsy/unprovoked seizures, with an overall RR of 2.19 (95% CI: 1.83–2.63), and a dose–response relationship (Samokhvalov et al., 2010).

CARDIOVASCULAR DISORDERS

A 2018 meta-analysis demonstrated that in men, any amount of alcohol consumption was associated with an increased risk for hypertension (Roerecke et al., 2018), indicating a previously unexplored sex-specific association between its intake and the disease incidence. At the same time, studies have suggested that Asian men may be even more prone to develop hypertension with low alcohol consumption when compared to Western men (Jung et al., 2020). A well-documented positive relationship also exists between heavy alcohol use (≥2 drinks/day) and hypertension in both sexes. Recently, a meta-analysis showed that a reduction in intake in those who drank heavily led to a significant decrease in their blood pressure; thus, a 50% intake reduction in patients who drank six or more drinks/day caused a decrease of 5.50 mmHg in systolic blood pressure and 3.97 mmHg in diastolic blood pressure (Roerecke et al., 2017). Moreover, alcohol use has also been associated with a higher risk of fatal hypertensive disease (HR 1.24, 1.15–1.33) (Wood et al., 2018).

Observational studies tend to show inconsistent findings between alcohol intake and the risk of stroke; recent meta-analyses have acknowledged that its use increases the incidence and mortality of stroke for both sexes in a dose–response manner, with a J-shaped relationship. However, the beginning of its detrimental influence appears to differ between men and women, with deleterious outcomes starting at moderate drinking in men, but only developing with heavy use in women, compared to non-drinkers. In a combined analysis of 599.912 current drinkers, Wood et al. found a roughly linear association between alcohol use and the risk of stroke, with an HR of 1.14 per 100 g/week higher use (95% CI: 1.1–1.17) (Wood et al., 2018). A 2016 meta-analysis found that light to moderate alcohol consumption (up to 2 drinks/day) was associated with a reduced risk only in ischemic stroke, whereas heavy alcohol use was associated with an increased risk of all stroke types, but with a stronger association for the hemorrhagic group (Larsson et al., 2016).

Most evidence over the years has suggested that alcohol use may play a cardioprotective role against coronary heart disease (CHD), with data supporting a 24–35% risk reduction with low to moderate consumption (Ronksley et al., 2011), and a 10–40% lower risk for those who consume 1–3 drinks/day (Rimm et al., 1999). Moreover, a 2015 meta-analysis found a significantly decreased risk of CHD with alcohol intake (OR = 0.68; 95% CI: 0.59–0.78; P < 0.00001) (Zhang et al., 2015). However, in the Wood et al. study alcohol use was found to be associated with an increased risk of CHD, when excluding myocardial infarction (HR 1.06, 1.00–1.11). Similar to what had been reported before, a lower risk for myocardial infarction was found (HR 0.94, 0.91–0.97) (Wood et al., 2018). Simultaneously, a 2017 fully adjusted meta-analysis of 45 studies found significantly reduced CHD mortality for current low-volume drinkers (RR = 0.80, 95% CI: 0.69–0.93) and all current drinkers (RR = 0.88, 95% CI: 0.78–0.99). Nonetheless, in stratified analyses, this consumption was not significantly protective for cohorts aged 55 years or younger at baseline (RR = 0.95, 95% CI: 0.75–1.21), nor for studies controlling for heart health (RR = 0.87, 95% CI: 0.71–1.06) (Zhao et al., 2017), findings that may mirror systematic selection biases acquired over the life span. Concerning drinking patterns, a 2018 meta-analysis found that inconsistently moderate drinkers had a significantly greater risk of incident CHD (HR = 1.18, 95% CI:  1.02–1.37) when compared to consistently moderate drinkers (O’Neill et al., 2018).

The effects of alcohol on induction of arrhythmias, especially those supraventricular, appear to be dose-dependent and independent of preexisting cardiovascular diseases. According to a 2017 systematic review and meta-analysis regarding atrial fibrillation (AF), high levels of alcohol intake seem to be associated with an increased AF risk in both sexes (HR 1.34, 95% CI: 1.20–1.49, P < 0.001), whereas moderate levels of alcohol intake are associated with an increased AF risk only in males (HR 1.26, 95% CI: 1.04–1.54, P = 0.02). Low intake does not appear to be associated with AF development (HR 0.95, 95% CI: 0.85–1.06, P = 0.37) (Gallagher et al., 2017). Daily alcohol consumption has also been linked to atrial remodeling and heavy use to less successful outcomes when ablation therapy is needed. Chronic alcohol use may also prolong the QT interval, creating a potential substrate for fatal ventricular arrhythmias (Qiao et al., 2015).

Long-term heavy alcohol consumption (5–15 years) is associated with alcohol-related cardiomyopathy (ACM), a condition in which ethanol and its first metabolite, acetaldehyde, act as direct toxins to the heart muscle, creating myocyte loss and dysfunction. It is characterized by changes in the left ventricle (dilation, increased mass and reduced or normal wall thickness) that impair myocardial contractility. In 2017, a systematic review confirmed this relationship and found that asymptomatic ACM was associated with chronic alcohol intakes of 80 g/day or more in men, proposing that quantity as a threshold (Rehm et al., 2017).

RESPIRATORY DISORDERS

Alcohol use appears to act as a risk factor for community-acquired pneumonia (CAP), as it may increase the risk of microbes aspiration by reducing oropharyngeal tone, modifying zinc bioavailability within the alveolar space and impairing macrophage function. A 2018 systematic review of 14 studies found a 1.8-fold increased risk in acquiring CAP among people who consume alcohol compared to those who do not, with an 8% incremental risk for each 10–20 g of daily alcohol intake (Simou et al., 2018a).

Some evidence has found an association between alcohol consumption and the risk of acute respiratory distress syndrome (ARDS). In 2018, Simou et al. conducted a systematic review and meta-analysis founding that patients with high alcohol consumption (defined as either alcohol abuse or high vs. low/none intake) had an increased risk of developing ARDS (OR, 1.89; 95% CI: 1.45–2.48) (Simou et al., 2018b). It has also been hypothesized that alcohol use may be involved in the pathogenic cause of more than 50% of ARDS’ cases. Although the mechanisms by which alcohol use may increase the aforementioned risk are still not fully understood, several different explanations have been proposed, such as an impairment of macrophage function, excessive oxidative stress, increased activity of the enzyme xanthine oxidoreductase, glutathione depletion, changes in lung epithelial barrier and toll-like receptor up-regulation, among others (Fini et al., 2017).

The use of alcohol also has a clinical impact on patients with Obstructive Sleep Apnoea (OSA). Alcohol reduces genioglossus muscle tone predisposing to upper airway collapse. It may also prompt an elevated dietary energy intake and a subsequent higher body mass index (BMI), two known risk factors for OSA. In 2018, a meta-analysis of 31 studies found that the overall risk of OSA was increased by 25% with alcohol consumption (Simou et al., 2018c), whereas another meta-analysis published that the same year showed a 33% risk increase among alcohol users when compared to abstainers (Taveira et al., 2018). Furthermore, studies have found that higher alcohol intakes may increase the chance of a more severe OSA and negatively impact breathing parameters such as the mean oxyhemoglobin saturation (SpO₂) during sleep (Kolla et al., 2018).

RENAL AND UROLOGICAL DISORDERS

Alcohol use does not appear to constitute a risk factor for chronic kidney disease (CKD). Furthermore, it has been found that alcohol drinking is associated with a 12–24% decreased risk of CKD, even with high levels of consumption (2 or more drinks/day) (Li et al., 2019). As stated before, alcohol consumption may increase HDL and plasma endogenous tissue-type plasminogen activator levels, as well as decrease platelet aggregation, mechanisms that are thought to be involved in the risk reduction. As for kidney cancer, meta- have also shown an inverse association between alcohol use and renal cell carcinoma (RCC) (OR 0.67, 95% CI: 0.62–0.73), with the greatest reduction at moderate drinking levels (Cheng and Xie, 2011). Moreover, Xu et al. found that each 5 g/day increment of alcohol intake was related to a 5% decrease in risk of RCC for males and 9% for females, which may imply a gender-specific relation (Xu et al., 2015).

The little existing data on the effect of alcohol use and the risk of urinary incontinence (UI) remain inconsistent. On the one hand, a Japanese study of 300 women aged 40–75 years found a statistically non-significant 30% UI increased risk for alcohol drinking and a 70% risk increase for ethanol intakes above 32 g/day when compared to non-drinkers (Lee and Hirayama, 2012), and, on the other hand, another Japanese study (in men) found an inverse association between UI and alcohol intakes of up to 32 g/day, showing almost a 60% risk reduction with that type of consumption (Lee and Hirayama, 2011).

Alcohol use appears to be inversely related to urolithiasis risk, which may be partially explained by its capacity to dilute metabolites and its diuretic effect. In a 2015 meta-analysis, Wang et al. demonstrated a 10% decrease in the risk of urolithiasis with each 10 g/day increase in alcohol consumption (Wang et al., 2015b), similar to what was found in an 8-year prospective cohort study conducted in American women, that showed a 59% decrease in kidney stone risk with every 240 ml intake of red wine (Curhan et al., 1988).

Although the association between alcohol consumption and erectile dysfunction (ED) has been discussed for a long time, there is no clear evidence to document this association. Even a meta-analysis concluded that light to moderate alcohol consumption (<21 drinks/week) was correlated with a decreased risk of ED (OR = 0.71; 95% CI: 0.59–0.86; P = 0.000), whereas high alcohol consumption (>21 drinks/week) was not (Wang et al., 2018).

ENDOCRINE SYSTEM

Studies have established that low to moderate alcohol consumption has a protective factor against type 2 diabetes mellitus (T2DM), reducing by 33–56% its incidence, by 34–55% the appearance of diabetes-related CHD, and lowering the risk of total mortality in patients already diagnosed with T2DM (Koppes et al., 2006). However, a 2015 meta-analysis of 38 observational studies found that the reduction in risk among moderate alcohol drinkers may be restricted to women and non-Asian populations only (Knott et al., 2015), results that agree with those found by Seike et al., who identified alcohol intake as an established risk factor for T2DM in lean Japanese men (with a BMI of ≤22.0 kg/m²) (Seike et al., 2008). At the same time, drinking patterns should also be taken into consideration, as it has been found that BD may increase the incidence of T2DM, as opposed to what allegedly happens with steadier consumption. Finally, acute intake of alcohol may increase the risk of hypoglycemia in patients already diagnosed with T2DM and treated with sulphonylureas, so special attention should be paid to this group (Pietraszek et al., 2010).

Chronic alcohol consumption is an important risk factor for low bone density, as it provokes both direct and indirect deleterious effects upon its structure. In 2019, a meta-analysis demonstrated a positive relationship between alcohol intake and osteoporosis, showing that those who consumed 1–2 drinks per day had 1.34 times the risk of developing this disease (95% CI: 1.11–1.62), while those who drank two drinks or more per day had 1.63 times the risk (95% CI: 1.01–2.65) (Cheraghi et al., 2019). Also, alcohol use is an important risk factor for developing gout, especially if the chosen beverage is beer. Both Li and Wang (Wang et al., 2013; Li et al., 2018) conducted meta-analyses examining the relationship between alcohol use and the incidence of gout, finding a 2- to 2.5-fold risk increase. Simultaneously, all types of alcoholic beverages have been associated with an increased risk of recurring gout flares in patients with already diagnosed gout, with a dose–response relationship and an effect likely to occur within 24 h of its consumption (Wang et al., 2013).

SKELETAL MUSCLE DYSFUNCTION

The association between excessive alcohol consumption and skeletal muscle dysfunction appears to be related by both direct and indirect mechanisms to impaired skeletal muscle protein metabolism.

Alcohol intake causes gut microbiota dysbiosis, reducing bacteroidetes and lactobacillus and increasing proteobacteria, fusobacteria and bacilli species. This dysbiosis subsequently increases intestinal permeability and circulating endotoxins, having the potential to cause or progress liver diseases and further disruptions in liver metabolism (Prokopidis and Witard, 2021).

It has been proposed that some catabolic mechanisms are impaired in alcohol abuse, such as ureagenesis and hepatocyte injury, causing hyperammonemia, which leads to up-regulated autophagy and impairs muscle protein synthesis. In some murine models, it has been demonstrated that alcohol consumption impairs muscle protein synthesis via decreased activation of mTORC1, ribosomal protein S6 kinase 1 and eukaryotic translation initiation factor 4E binding protein 1; nevertheless, this has to be proven in human trials (Prokopidis and Witard, 2021).

Finally, increased endotoxins and pro-inflammatory cytokine secretion induce muscle atrophy and mitochondrial dysfunction, which is prevalent in muscle wasting conditions (Prokopidis and Witard, 2021).

HEMATOLOGICAL DISORDERS

Alcohol use may cause multiple hematological disturbances that may even appear after acute drinking episodes in non-cirrhotics patients (Myrhed et al., 1977). Megaloblastic macrocytic anemia is frequently seen, and it is thought to be mainly caused by folate deficiency. Vitamin B12 deficiency, gastrointestinal bleeding, extracorpuscular hemolysis due to hypersplenism and direct toxicity on erythropoiesis have also been listed as contributing factors. Leukopenia and thrombocytopenia may also be identified, an element of importance given that this combination has been associated with an increase in both morbidity and mortality in compensated cirrhotics (Qamar et al., 2009). Furthermore, an increase in reticulocytes, erythrocyte sedimentation rate, prothrombin time and percentage of saturation of serum iron-binding protein have also been described. In patients with chronic alcohol use, the presence of Zieve’s syndrome should be considered when the triad of hemolytic anemia, cholestatic jaundice and hyperlipidemia is present. Zieve’s syndrome represents an underdiagnosed condition, and its early recognition is essential, as it may prevent unnecessary interventions and prompt alcohol cessation, its most effective treatment (Abughanimeh et al., 2019). Regarding myelodysplastic syndromes, some studies have found an increased risk associated with its intake. However, evidence still remains inconclusive (Sweeney et al., 2019).

INFECTIOUS DISEASES

Alcohol intake is strongly associated with risky sexual behavior, which may favor the appearance of human immunodeficiency virus (HIV)/AIDS. Furthermore, its use may decrease the adherence to antiretroviral medication, leading to viral load increases and a decrease in CD4 count (Vagenas et al., 2015). It has also been proposed that alcohol consumption itself may enhance viral replication and impair immunity, creating a pro-inflammatory state that may prompt HIV disease progression. Thus, a 2010 meta-analysis found a 77% higher risk of HIV (RR = 1.77, 95% CI: 1.43–2.19) for alcohol consumers as well as an 87% increased risk (RR = 1.87, 95% CI: 1.39–2.50) for those consuming alcohol prior to, or at the time of, sexual relations. BD appeared to be another important factor, doubling the risk by itself (RR = 2.20, 95% CI: 1.29–3.74) (Baliunas et al., 2010).

Another infectious disease that has been associated with alcohol consumption is tuberculosis (TB). Around 10% of the world’s TB cases may be attributable to alcohol, as its consumption seems to increase susceptibility to both primary infection and reactivation of disease (Rehm et al., 2009). A 2018 meta-analysis demonstrated 90% higher odds of TB risk in relation to alcohol use, as well as a 12% risk increase for every 10–20 g of daily alcohol intake (Simou et al., 2018d). These results contrast with those found by Imtiaz et al., who evidenced a 35% increase in risk among consumers (Rajendran et al., 2020). In 2014, Patra et al. reported that any drinking was associated with a 50% increased risk of TB symptoms in women and a 26% increased risk in men (Patra et al., 2014). Furthermore, alcohol use has been associated with a 2.54 times higher probability of having multidrug-resistant TB and with 1.5- to 2-fold increased odds of poor treatment outcomes; it may also represent a risk factor for TB infectiousness and increase the risk of death from TB (Ragan et al., 2020).

ALCOHOL CONSUMPTION BIOMARKERS

In the follow-up of patients who have started treatment against AUD, BD or ALD, it is of great importance to corroborate the maintenance of abstinence from alcohol consumption. The first and main form of research is through the clinical interview in the presence of a family member, caregiver or companion of the patient. However, this can underestimate or minimize the actual consumption of alcohol, especially because of the social stigma that this entails. In this sense, there are indirect markers of alcohol consumption with low specificity but high availability for use in routine clinical practice, such as elevated serum levels of y-glutamyl transpeptidase, aspartate aminotransferases or carbohydrate-deficient transferrin. On the other hand, direct biomarkers include acetaldehyde, acetic acid, fatty acid ethyl ester, serum phosphatidylethanol (PEth), ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine; they present a specificity of over 90% with variable yields depending on the timing of sampling and consumption. In the case of urine EtS and EtG, they may be detectable in urine up to 90 h after alcohol ingestion. Conversely, PEth presents a sensitivity of over 90% with a specificity of 100% for the presence of alcohol consumption in the last 28 days (Lucey, 2014; Arab et al., 2021). Given their potential aid in diagnosis and treatment, caregivers should be further familiarized with their existence.

CONCLUSION

Alcohol use is a part of many cultural and social practices, providing perceived pleasure to many users. Nevertheless, alcohol abuse can impact population health on many levels, not only in chronic liver disease, but also in cardiovascular diseases, cancer and neuropsychiatric disorders. As healthcare providers, we must identify populations at high risk of alcohol abuse, educate patients about the potential alcohol-related harm and provide appropriate treatment.

CONFLICT OF INTEREST STATEMENT

None declared.

References

Author notes