Alcoholic liver disease

Alcoholic liver disease (ALD) is an umbrella term for liver conditions caused by significant and chronic alcohol abuse. It initially causes liver steatosis, which progresses to alcoholic hepatitis to cirrhosis unless alcohol consumption stops.

Almost all who abuse alcohol develop liver steatosis, which is reversible, but only a few progress to hepatitis and cirrhosis. Hepatitis C is often found in chronic alcoholics and leads to acceleration of alcoholic liver disease.

Excessive ethanol consumption causes more than 60 % of chronic liver diseases in the Western countries and is the 5th leading cause of death. Alcoholic liver disease is a major cause of liver transplantation.

Etiology

Alcoholic liver disease is caused by significant alcohol consumption over long periods of time. The risk increases proportionally with the amount of alcohol consumed. There is no threshold above which ALD invariably develops, as this varies from person to person, but most people with ALD have been drinking ~10 units daily for decades.

According to the lecture (and they like to ask this), these are the “limits” for alcohol consumption:

• Females: 7 – 13 units/week = 10 – 20 g alcohol per day
• Males: 14 – 27 units/week = 20 – 30 g alcohol per day

When talking about alcohol consumption, it’s important to define how much a unit of alcohol is. In Europe in general, one unit is 10 g of alcohol, while it’s 14 g in the US. This corresponds to 250 ml beer, 100 ml of wine, or 30 ml of 40% hard liquor. In 100 ml of beer, there is 4 g of alcohol.

Some “fun facts” about alcohol drinking: women are more susceptible to alcohol-induced liver injury, and binge drinking may be as harmful as daily drinking.

Pathology

Hepatocellular steatosis results from shunting substrates away from catabolism and towards lipid synthesis, because alcohol dehydrogenase generates so much NADH from all the ethanol that lipid synthesis is favoured by the metabolism.

The causes of alcoholic hepatitis are most likely toxic products and metabolites from ethanol metabolism, like:

• Acetaldehyde
• Reactive oxygen species generated during oxidation of ethanol
• Cytokine-mediated inflammation and cell injury
• Alcohol itself

The progression of alcoholic liver disease is as follows:

• Hepatocellular steatosis
  • Macroscopically, the liver is very big (4-6 kg or more), soft, yellow and greasy.
• Steatohepatitis
  • Hepatocyte ballooning, where single or scattered foci of hepatocytes undergo swelling and necrosis.
  • Mallory-Denk bodies, which consists of damaged intermediate filaments, and can be seen as very eosinophilic inclusion bodies in degenerating hepatocytes
  • Neutrophil infiltration – neutrophils accumulate around the degenerating hepatocytes. Especially around the Mallory-Denk bodies.
• Cirrhosis

The area around the central veins are most susceptible to toxic injury because the generation of acetaldehyde and free radicals is biggest there. Pericellular and sinusoidal fibrosis develop in this area as well. Both steatosis and alcoholic hepatitis can be reversible if the patient stops drinking alcohol.

Clinical features

The symptoms depend on the pathological stage:

• Alcoholic steatosis
  • Mostly asymptomatic
  • Nontender hepatomegaly
• Alcoholic steatohepatitis
  • Non-specific symptoms like nausea, loss of appetite, weight loss
  • Tender hepatomegaly
  • Jaundice
• Alcoholic cirrhosis
  • General symptoms of cirrhosis

Some cases of alcoholic liver disease are detected incidentally in the cirrhosis stage.

It’s important to keep in mind that alcohol abuse is dangerous to all organ systems, and symptoms of e.g. cardiomyopathy, neuropathy, and encephalopathy may be present.

Diagnosis and evaluation

For diagnosis of alcoholic liver disease, it’s important to establish the diagnosis of alcohol abuse, in which case heteroanamnesis may be required. The following laboratory alterations are typical:

• AST/ALT ratio > 2 (but both are elevated)
• Macrocytic anaemia
• Elevated GGTs

Serum ethanol levels can be measured, but this only elevated in case of intake in the last hours. Phosphatidylethanol (PEth), a phospholipid which is only formed after alcohol consumption, is a marker of long-term alcohol intake. Carbohydrate-deficient transferrin (CDT) is another marker of long-term alcohol intake.

Ultrasound show characteristic findings depending on the stage. However, it cannot determine whether the cause of liver disease is alcoholic:

• Steatosis – hepatomegaly, increased liver echogenicity
• Steatohepatitis – larger hepatomegaly, periportal oedema
• Cirrhosis – nodular liver surface, atrophy, loss of structural homogeneity

CT and MRI, as well as special techniques like FibroScan, transient elastography (TE) and acoustic radiation force impulse (ARFI) may also be used.

It’s important to rule out other causes of liver disease, including viral and autoimmune.

Treatment

Abstinence is essential to reverse early stages of alcoholic liver disease and to prevent progression in later stages. Abstinence is difficult, and both non-pharmacological and pharmacological interventions should be utilised to achieve it.

In case of hepatitis, glucocorticoids may be helpful in severe cases to reduce mortality.

Other treatments which may be useful:

• Metadoxine – a drug which may increase alcohol elimination and may have a beneficial effect on ALD
• N-acetylcysteine
• Hepatoprotective antioxidants

Regular screening for cirrhosis, oesophageal varices, and hepatocellular carcinoma is indicated. If cirrhosis has developed, treatment aims at preventing complications like ascites, varices, and encephalopathy.