Hospital admissions due to alcohol consumption have risen dramatically in Ireland, increasing by 92% from 1995-2002, with approximately 10% of all general inpatient hospital costs, 7% of GP costs and up to 30% of emergency department costs directly attributable to alcohol. 

Alcohol-related liver disease increased by 190% between 1995-2007, with a worrying trend among younger age groups (247% increase among 15-34-year-olds).¹

Alcohol consumption can be divided into:

• Moderate (less than three to four units/day for men, one to two units/day for women) 

• Harmful (causing mental or physical damage)

• Hazardous (increasing risk of harm)

• Dependence (cluster of behavioural, cognitive and physiological factors including a strong desire to drink alcohol and persist in drinking, despite harmful consequences).²

Alcohol can cause a wide variety of gastrointestinal (GI) symptoms and lead to both acute and chronic GI diseases that carry significant morbidity and mortality. 

Oesophagus and stomach

Alcohol consumption has a direct effect on the oesophagus, relaxing the lower oesophageal sphincter which increases gastro-oesophageal reflux, leading to oesophagitis. Similarly, alcohol can affect gastric emptying, with higher alcohol concentrations delaying emptying and lower concentrations inducing emptying. Following alcohol bingeing, vomiting can lead to Mallory-Weiss syndrome, which consists of tears of the mucosa in the lower part of the oesophagus.³

Alcohol can cause superficial inflammation of gastric mucosa, gastritis and, while it has not been implicated in the formation of ulcers, it can impair the healing of ulcers. The relationship between alcohol and gastric acid production appears to be related to the type of alcohol with fermented alcoholic beverages stimulating acid and gastrin production, whereas distilled beverages have no effect. 

It is postulated that distillation either removes compounds that stimulate acid, or distillation produces compounds that inhibit alcohol.⁴

Historically, red wine was viewed to have bactericidal properties, and was considered to protect against GI infections. While red wine has in vitro activity against bacteria that cause diarrhoeal illness, there is no convincing evidence that drinking red wine will prevent traveller’s diarrhoea or gastroenteritis. 

However, red wine has been shown to be protective against Helicobacter pylori infection, which is a common cause of gastric ulceration.⁵

Diarrhoea and nutrition

Diarrhoea and malabsorption are common GI symptoms reported by those with alcohol dependence. The mechanism for diarrhoea is multifactorial, with decreases in enzymes such as disaccharidases and increases in small intestine permeability, that allow more fluid to enter the intestinal lumen. 

The increased permeability can be reversed with just one to two weeks of abstinence. The small bowel of alcoholics has been found to contain more bacteria that produce endotoxins leading to higher levels of endotoxins in the bloodstream of alcoholics, which contributes to the development of chronic liver disease.⁴

Steatorrhoea is less common than diarrhoea, and is generally due to pancreatic insufficiency. Malabsorption and malnutrition in alcoholics is well described, but seems to be largely due to dietary deficiencies. 

However, certain nutrients are directly affected by alcohol. Thiamine absorption is inhibited by alcohol at a cellular level, with alcohol inhibiting the transport mechanism, the ATPase in the vasolateral membrane of the epithelial cell. 

Vitamin B12 absorption is affected by chronic alcohol consumption, with reduced levels of intrinsic factor which binds to vitamin B12 in the terminal ileum. Alcohol decreases calcium absorption in the duodenum and also causes increased excretion of zinc in the urine.⁴

Thiamine deficiency leads to Wernicke-Korsakoff syndrome, an acute syndrome of confusion, eye signs and ataxia which may lead to, or co-exist with, a chronic syndrome of retrograde and anterograde amnesia. Given the devastating consequences of Wernicke-Korsakoff, it is imperative to aggressively treat thiamine deficiency. Oral thiamine absorption is limited by an active transport process, with a single dose of 10-30mg maximising absorption. After alcohol cessation, it can take up to six weeks for this transport mechanism to return to normal.

Prophylactic thiamine should be given to any patient with excess alcohol consumption and any of these risk factors: acute alcohol withdrawal; liver disease; hospitalised for any reason; malnutrition, including weight loss; loss of appetite; nausea or vomiting. The dose of oral or parenteral thiamine (Pabrinex) should be given at the higher end of the BNF recommendations and parenteral thiamine therapy, eg. Pabrinex I+2, bd or tds, should always to followed with oral therapy, eg. thiamine 100mg tds). Patients should not receive intravenous dextrose without concomitant thiamine.²

Gastrointestinal cancer risk

Alcohol consumption has been directly linked to cancer of the oral cavity, pharynx, oesophagus, stomach and upper airways. Alcohol increases cancer risk through many mechanisms, including direct cytotoxicity, producing aberrant methylation of DNA, effects on immune surveillance, and also is metabolised to acetaldehyde, which generates free radicals promoting tumour development. Some compounds, the polyphenols, found particularly in wine, have been shown have antioxidant and anticancer properties.⁴ Moderate wine intake has been found to have no effect on upper GI cancer, while moderate beer or spirit intake increased upper GI risk substantially (RR 5.2 versus 1.7 compared to non-drinkers).⁶

Moderate alcohol intake increases the risk for both colorectal cancers and adenomas, with some studies finding reductions in the risk for wine compared with beer or spirits.⁴ Cancer risk is increased with smoking, probably through smoking’s synergistic effect on acetaldehyde. Alcohol liver disease leads to cirrhosis, which carries a significant liver cancer risk. Alcohol has also been implicated in breast cancer risk.⁸

Effects on the pancreas

Alcohol damages the pancreas, with patients either presenting with acute or chronic pancreatitis. The acinar cells of the pancreas metabolise alcohol and the pancreatic stellate cells, which cause fibrosis, are activated by alcohol and acetaldehyde. Repeated cycles of pancreatic inflammation lead to acinar atrophy and fibrosis, causing chronic pancreatitis with chronic endocrine and exocrine insufficiency, with diabetes and steatorrhoea as well as chronic abdominal pain.

Acute pancreatitis presents with abdominal pain, nausea and vomiting, sometimes leading to metabolic derangements and shock with complications such as jaundice, pseudocyst formation and diabetes common. Hospital admissions in Ireland for acute alcohol pancreatitis increased by 54% between 1997-2004.¹ Smoking increases the risk and rate of progression of chronic alcoholic pancreatitis as well as pancreatic cancer.⁸

Liver reactions

Alcohol is metabolised primarily by three pathways in the liver: the alcohol and aldehyde dehydrogenase pathways metabolise 90% of alcohol; and the microsomal ethanol-oxidizing system, through the cytochrome P450 CYP2E1.

Alcohol dehydrogenase catalyses the oxidation of ethanol to acetaldehyde and the transferring of hydrogen to the cofactor nicotinamide adenine dinucleotide (NAD), which is converted to its reduced form, NADH. The resulting increase in the NADH/NAD ratio affects gluconeogenesis and plays a major role in the initial pathogenesis of alcohol-induced fatty liver by affecting how the liver metabolises fatty acids. The activity of cytochrome CYP2E1 increases with chronic alcohol use, which explains the differences in drug metabolism in alcoholics, especially paracetamol. 

The first pathological stage of alcohol-related liver disease (ALD) is fatty liver (hepatic steatosis) which is marked by the accumulation of lipid within the hepatocyte. Abstinence can reverse steatosis to normal liver. The second pathological stage is steatohepatitis or alcoholic hepatitis, which is characterised by an inflammatory reaction with leucocytes and hepatic necrosis. This inflammatory reaction is in part from the endotoxins in the gut entering the portal circulation and stimulating cytokines within the liver, leading to oxidative stress, hepatic stellate cell activation, proliferation and collagen synthesis, which leads to fibrosis. Other mechanisms include the induction of hepatocyte apoptosis by the cytokine TNF-α and the production of acetaldehyde.

The final stage of ALD is fibrosis and then cirrhosis. The activation of hepatic stellate cells is a key stage in the development of cirrhosis. There is a definite genetic susceptibility to alcoholic liver disease, given a third of heavy drinkers will develop alcoholic hepatitis but only between one in four and one in 12 ever progress to cirrhosis. A variety of genetic polymorphisms have been implicated including genes encoding alcohol dehydrogenases, cytokine and immune responses. 

Alcohol consumption of at least 40-80g/day for males and 20-40g/day for females for 10-12 years will definitely lead to alcoholic liver disease, however, there is no definite prediction for liver disease from alcohol consumption. Certain drinking behaviours such as binge drinking, drinking outside of meal times, and drinking spirits and beer versus wine increase the risk of ALD, as does female gender, possibly due to a lower level of gastric ADH or a higher body fat proportion. 

Malnutrition, both protein calorie and micronutrient malnutrition, particularly vitamins A and E, aggravates ALD, and so does obesity, probably through increasing fatty liver. 

Continued alcohol intake once alcoholic hepatitis or cirrhosis is diagnosed has a definite impact on survival. Alcohol abuse significantly worsens outcomes in viral hepatitis or other causes of liver disease.⁹

Not all patients with fatty liver who develop cirrhosis will develop alcoholic hepatitis and, in those that do, there is a wide clinical spectrum from mild injury to severe disease, with up to 50% having concomitant cirrhosis.¹⁰

Alcohol liver disease is diagnosed clinically, with evidence of both alcohol excess and liver disease. Elevated serum aminotransferases of two to six times the upper limits of normal are common in severe alcoholic hepatitis. Levels of AST > 500IU/L or an ALT > 200IU/L are uncommonly seen with alcoholic hepatitis and should suggest another aetiology. An AST/ALT ratio of > 3 is suggestive of ALD.

Patients with alcoholic hepatitis will generally have a long history of excessive alcohol consumption  and present with jaundice and symptoms such as fever, nausea, anorexia, fatigue, pruritus, weakness, right upper quadrant pain and confusion.  A scoring system such as Maddrey’s discriminant function (DF) based on bilirubin and PT is helpful to determine who should receive treatment. A score of > 32 is associated with 30-50% mortality at one month. 

Another popular scoring system is the Glasgow Alcoholic Hepatitis Score. Patients without evidence of infection, bleeding or renal failure, and a DF of > 32 should receive steroids (40mg prednisolone per day for one month). Abstinence is key for all patients, and all should receive aggressive nutritional support. Those with contraindications to steroids, or with severe disease, should be considered for pentoxifylline (400mg tds for one month).¹⁰

Hepatocellular carcinoma develops in 5-15% of those with alcoholic cirrhosis. Decompensated alcoholic cirrhosis and its complications – variceal bleeding, encephalopathy, spontaneous bacterial peritonitis – should be treated with standard medical therapy and, generally after a period of abstinence of at least six months, can be considered for liver transplantation.¹⁰

Conclusion

Excess alcohol consumption can cause many gastrointestinal symptoms from reflux, vomiting and diarrhoea to life-threatening illnesses such as cancer, acute pancreatitis, alcoholic hepatitis and cirrhosis. As alcohol consumption continues to increase in Ireland, the treatment of the GI-related complications will prove challenging.  

References

1. Hope A. Alcohol-related harm in Ireland. Health Service Executive – Alcohol Implementation Group. 2008. Available from: http://www.yourdrinking.ie/reports/HPR00507.pdf
2. RCP (UK). Alcohol Use Disorders: Diagnosis And Clinical Management Of Alcohol-Related Physical Complications. Clinical Guideline 100. 2010. Available from: http://www.nice.org.uk/nicemedia/live/12995/48989/48989.pdf
3. Stermer E. Alcohol consumption and the gastrointestinal tract. Isr Med Assoc J 2002; 4(3): 200-202
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5. Brenner H, Rothenbacher D, Bode G, Adler G. Inverse graded relation between alcohol consumption and active infection with Helicobacter pylori. Am J Epidemiol 1999; 149(6): 571-576 
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7. Maisonneuve P, Lowenfels AB, Müllhaupt B et al. Cigarette smoking accelerates progression of alcoholic chronic pancreatitis. Gut 2005; 54(4): 510-514 
8. Pöschl G, Seitz HK. Alcohol and Cancer. Alcohol and Alcoholism 2004; 39(3): 155-165
9. Gramenzi A, Caputo F, Biselli M et al. Review article: alcoholic liver disease? pathophysiological aspects and risk factors. Alimentary Pharmacology and Therapeutics 2006; 24(8): 1151-1161 
10. O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology 2010; 51(1): 307-328