Alcoholic liver disease (ALD) | causes and management

Alcoholic liver disease is often silent until complications develop; therefore clinicians need a high index of suspicion to detect individuals with heavy alcohol consumption and evolving liver disease. At a population level, strategies to reduce per capita alcohol consumption can be expected to reduce mortality from alcohol related disease. At an individual level, early diagnosis, abstinence and effective treatment of complications are pivotal to reducing mortality.
Alcoholic liver disease is often silent until complications develop



Levels of alcohol intake

Recording of alcohol intake is standardized at units of 10 g per day, roughly the content of a standard drink from a glass of beer to a wine glass or a nip of spirits. Based on epidemiological data and modelling of lifetime risks from alcohol consumption the most recent National Health and Medical 




Research Council guidelines recommend: ‘For healthy men and women, drinking no more than two standard drinks on any day reduces your risk of harm from alcohol-related disease or injury over a lifetime’. Cirrhosis will occur earlier in the presence of cofactors for cirrhosis such as viral hepatitis, obesity or iron overload. Paradoxically, there is evidence that the mortality curve relating to alcohol intake is a J curve. In males, mortality is lowest at an intake of two units per day after which it rises steeply.

What is Alcoholic Liver Disease?


As the name implies, alcoholic liver disease is liver injury attributed to alcohol abuse. The majority of Americans manage to drink alcohol without serious consequences. Research suggests, however, that liver disease may begin to develop after a "threshold" dose of alcohol has been consumed generally assumed to be four drinks a day (four 12 ounces beers, four glasses of wine, or four ounces of hard liquor) for men, and one half that quantity for women. Nearly everyone who consumes this amount or more will have some evidence of liver injury, although less than 50% will develop serious liver disease.

Types of alcoholic liver disease


Fatty liver due to alcohol
Fatty liver due to alcohol is usually asymptomatic but may be associated with mild nonspecific symptoms such as nausea. Its major feature is liver enlargement due to the accumulation of fat globules within hepatocytes, which can occur after a single occasion, or ‘binge’, of alcohol excess and usually regress with abstinence. Other causes of fatty liver include obesity, viral hepatitis and medications. It is therefore a diagnosis of exclusion.

Alcoholic hepatitis
Alcoholic hepatitis is characterised by acute inflammatory changes in the liver and symptoms varying from mild abdominal pain and fever to deep jaundice and coma. It is usually a consequence of binge drinking. Acute changes may reverse if alcohol is avoided. If heavy alcohol consumption continues it leads to cirrhosis. It is more commonly seen in those with concomitant advanced liver disease.

Alcoholic cirrhosis
Alcoholic cirrhosis is characterised by replacement of hepatocytes by fibrosis and the progressive destruction of the normal architecture and loss of liver function. It is generally the consequence of years of consistently heavy drinking and most often occurs in middle aged men. Cirrhosis is often silent until it presents with complications such as jaundice, bleeding from varices, ascites, infection or neuropsychiatric changes.

Causes

Genetics
Polymorphisms exist in the enzymes ADH, CYP2E1, and ALDH. Differences in ADH and ALDH certainly contribute to the negative association with ethanol dependence in some Asian populations. HLA phenotypes, a genetic predisposition toward alcoholism and female gender may also contribute to overall risk.

Viral Liver Disease
Concurrent viral hepatitis increases the incidence of liver injury in alcoholics. Studies have shown that alcoholics co-infected with hepatitis C virus (HCV), (but not necessarily hepatitis B virus), develop liver injury at a younger age and with a lower cumulative dose of alcohol than those not infected with HCV. These patients also have a much higher chance of developing cirrhosis and hepatocellular cancer compared to alcoholics without hepatitis C

Nutrition
Initial hypotheses suggested that alcoholic liver disease was a result of alcohol intake in the face of poor nutrition. Today, however, it is understood that while malnutrition may worsen the severity of disease and obesity may increase the risk of developing disease, alcoholic liver disease does indeed occur in well-nourished individuals. Nutrition probably plays a role in hepatotoxicity. 

Current research suggests that patients with diets deficient in essential nutrients are more susceptible to the development of liver damage. Alcohol ingestion promotes the absorption of iron from the intestine, increasing hepatic iron stores. Iron acts as an electron donor, accelerating the generation of unstable free oxygen radicals. In addition to contributing to membrane injury, this may also exacerbate inflammatory response.

Hepatotoxin Exposure
In general, two insults are worse than one. Just as viral hepatitis increases the risk to develop alcohol related liver injury, other hepatotoxins may act synergistically or additively with alcohol. This is especially true with acetaminophen and vitamin A overdose.

Examination
Alcohol excess can present as hypertension; this may be the only clue on examination (other than the smell of stale alcohol) that the patient is drinking at excessive levels. An enlarged and possibly tender liver may be another early sign of alcoholic liver disease.

Late signs of alcoholic liver disease include:
• Peripheral stigmata of chronic liver disease, including bruising, leukonychia (from hypoalbuminaemia), clubbing, palmar erythema, bruising, spider naevi gynaecomastia and testicular atrophy
• Signs specific to chronic alcoholism, including Dupuytren contracture, parotidomegaly and proximal myopathy
• Liver enlargement (unless cirrhosis is advanced)
• Signs of portal hypertension, including splenomegaly collateral veins and ascites
• Signs of cardiomyopathy
• The effects of exocrine pancreatic failure from alcohol induced chronic pancreatitis which result in pale, fatty motions which are difficult to flush away.

Management


Abstinence
If abstinence from alcohol can be achieved, the outlook, except in the presence of advanced cirrhosis, can be surprisingly good. Even in the presence of advanced disease, patients who become abstinent do better than those who continue to drink, with 5 year survival rates of over 50%. It is particularly important to counsel hepatitis C positive individuals about avoiding alcohol because of its synergistic effect.

Fatty liver due to alcohol and all but severe cases of alcoholic hepatitis will resolve with abstinence. Referral to a local drug and alcohol service for treatment (inpatient or outpatient) and/or medications may be needed to help achieve abstinence.

Nutrition
Malnutrition is frequent among individuals with advanced liver disease due to a combination of poor intake and increased requirements. Management should focus on correcting any vitamin deficiencies and ensuring that patients consume a high energy, high protein diet of 1.0–1.5 g of protein per kg of lean body weight, either by adjusting the content and frequency of meals and/or by the addition of high energy supplements. A snack before bed helps prevent the breakdown of muscle stores overnight. Patients who continue to drink should also receive thiamine supplementation to prevent Wernicke-Korsakoff syndrome.

Prescribing issues
An important prescribing issue is the extent of impaired liver function. In particular, people with cirrhosis are sensitive to sedatives and anticoagulants are contraindicated in those with decompensation. For the unrecognised cirrhotic, surgery and its postoperative course is dangerous. Many other medications can be hepatotoxic. It is important to educate the patient to check with their doctor before starting any new medications.




Reference
https://www.medicalnewstoday.com/articles/215638
https://medlineplus.gov/ency/article/000281.htm
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/alcoholic-liver-disease/
https://www.healthline.com/health/alcoholism/liver-disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513682/
https://www.nhs.uk/conditions/alcohol-related-liver-disease-arld/
https://www.mayoclinic.org/diseases-conditions/alcoholic-hepatitis/symptoms-causes/syc-20351388
https://www.addictioncampuses.com/alcohol/early-signs-liver-damage/
Alcoholic liver disease (ALD) | causes and management Alcoholic liver disease (ALD) | causes and management Reviewed by gafacom on July 10, 2020 Rating: 5

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