History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include prolonged heavy alcohol consumption, presence of hepatitis C, and female sex.

abdominal pain

Right upper abdominal discomfort is most common in patients with acute alcohol-related hepatitis.

hepatomegaly

May be present in patients with alcohol-related steatosis or alcohol-related hepatitis. Hepatomegaly may be an ominous sign in patients with cirrhosis, suggesting the presence of hepatocellular carcinoma.

uncommon

haematemesis and melaena

Signs of gastrointestinal bleeding, possibly related to oesophageal or gastric varices, gastric irritation, and coagulopathy.

venous collaterals

Engorged para-umbilical veins (caput medusae), present in advanced ARLD.

splenomegaly

May be present in advanced liver disease patients with portal hypertension.

hepatic mass

Ominous sign; may portend presence of hepatocellular carcinoma.

jaundice

Common in severe alcohol-related hepatitis and in decompensated severe alcohol-related cirrhosis. Uncommon in compensated alcohol-related cirrhosis or alcohol-related steatosis. However, co-existent intra- or extrahepatic cholestasis should also be considered.

palmar erythema

Affects the thenar and hypothenar eminences while sparing the central portions of the palm. It may be present in patients with ARLD.

cutaneous telangiectasia

Vascular spiders with central arteriole flanked by smaller vessels. Usually seen on the trunk, face, and upper limbs. It may be present in patients with advanced ARLD.

asterixis

Flapping motions of outstretched, dorsiflexed hands; quick test for encephalopathic state. It is one of the manifestations of hepatic encephalopathy present in advanced ARLD.

Other diagnostic factors

common

ascites

Very common clinical complication of cirrhosis. It can be evaluated by the presence of shifting dullness or fluid wave examination.

weight loss

High tumour necrosis factor (TNF)-alpha and inflammatory response is associated with ARLD and can lead to loss of appetite and weight loss.[64]

weight gain

Ascites and/or oedema can cause gradual unintentional weight gain in patients with ARLD with portal hypertension.

malnutrition and wasting

May manifest as loss of weight and muscle mass, or as vitamin deficiency.

anorexia

High tumour necrosis factor (TNF)-alpha and inflammatory response is associated with ARLD and can lead to loss of appetite.[64][65]

fatigue

Common in patients with co-existing chronic hepatitis. May be caused by the activation of peripheral pathways between the brain and liver, which leads to changes in brain neurotransmission.[66]

uncommon

confusion

Hepatic encephalopathy in advanced cirrhosis may manifest as impaired mentation.[67]

Agitation, loss of concentration, and impaired judgement may be part of mental confusion.

Thiamine deficiency associated with ARLD can lead to mental confusion and neurological complications, such as Wernicke-Korsakoff syndrome.

pruritus

Present in association with jaundice due to accumulation of bile salts in the skin layers. It may be significant enough to cause sleep disturbances.

fever

Low-grade fever can be present in patients with alcohol-related hepatitis in the absence of infection.[41]

nausea and vomiting

May be due to gastric irritation from alcohol- or cirrhosis-associated gastroparesis.

finger clubbing

Distal portion of digit takes on drumstick appearance.

Dupuytren's contracture

Characteristic palmar fascia contracture and thickening associated with severe liver disease.

leg swelling

Peripheral oedema commonplace in both renal and liver disease from salt retention, hypoalbuminaemia, osmotic changes.

parotid gland enlargement

Fatty infiltration of the gland with fibrosis and oedema, probably due to the extrahepatic toxicity of alcohol.

gynaecomastia

Present in nearly two-thirds of patients. Common symptom of chronic liver disease, manifestation of altered sex hormone metabolism.[68]

hypogonadism

Multifactorial in nature, and a common finding in advanced ARLD.

dementia

Warrants careful evaluation for thiamine deficiency.

peripheral neuropathy

Focal defects, including altered reflexes, may be present.

Peripheral neuropathy might be associated with the direct toxic effect of alcohol on nerve tissue but is more likely to be associated with nutritional deficiencies.

Risk factors

strong

prolonged and heavy alcohol consumption

The quantity of alcohol ingested and the duration are the most important risk factors for ARLD development.[1]

Although alcohol-induced liver injury is somewhat dose dependent, there is no set alcohol consumption threshold that reliably predicts the development of ARLD.​[1][13]​​ One meta-analysis reported increased risk for ARLD with alcohol consumption ≥280 g/week.[29]

Most heavy alcohol drinkers will never develop clinical liver disease. Only about 10% to 20% of chronic heavy drinkers develop severe forms of ARLD, such as alcohol-related hepatitis or cirrhosis.[1][14][15]​​

hepatitis C

Patients with ARLD with hepatitis C infection have more severe histological features, decreased survival, disease development at a younger age, and a higher incidence of hepatocellular carcinoma.[30][31]

female sex

ARLD develops more rapidly and occurs at lower drinking levels in women than in men.[13][15][32][33]​​​​​

However, most patients with ARLD are male.[29]

weak

cigarette smoking

Fibrosis progresses more rapidly in patients with ARLD who smoke.[20][29]

obesity

The risk of ARLD is at least 2 times higher in patients with obesity than in patients with a normal body mass index.[1][18][19]​​​​​ Even if abstinent, people with obesity are at an increased risk of steatotic liver disease. Obesity seems to be an independent risk factor for both alcohol-related hepatitis and alcohol-related cirrhosis.[18]

age >65 years

Alcohol metabolism and distribution change with age. An older person's liver is more susceptible to alcohol-related toxicity. However, within the spectrum of ARLD, the symptoms and signs are similar in patients of all ages. Prognosis for ARLD in older people (age >65 years) is poor.[34]

Hispanic ethnicity

Associated with a higher prevalence of ARLD.[35][36]

genetic predisposition

A number of cytokine and alcohol-metabolising enzyme gene polymorphisms (tumour necrosis factor-alpha 238G>A polymorphism, interleukin-6 gene polymorphisms, patatin-like phospholipase domain protein 3 gene polymorphism rs738409 C>G) may be associated with increased risk for ARLD.[22][23][24][15]

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