Alcohol-associated liver disease

This article is part of an accredited activity. For full CME information and disclosures, please click on the link in this reference: ^[1]

Alcohol-associated liver disease (ALD) refers to a spectrum of progressive liver conditions caused by chronic harmful alcohol use. One-third of the US population exceed moderate alcohol consumption, increasing their risk of ALD. Early ALD is typically asymptomatic and manifests with potentially reversible alcohol-associated steatosis or steatohepatitis. Continued alcohol consumption may lead to alcohol-associated hepatitis, which is characterized by acute jaundice, malaise, and fever. Patients with advanced ALD may develop alcohol-associated cirrhosis. Patient history, transaminase levels, and imaging are used to determine the stage of ALD. Management of ALD requires complete cessation of alcohol consumption.

The management of alcohol-associated hepatitis, including its diagnosis and treatment, is described in detail in “Alcohol-associated hepatitis.” The management of alcohol-related cirrhosis is described in “Cirrhosis.”

Alcohol-associated steatosis and mild alcohol-associated hepatitis may be reversible after cessation of alcohol consumption. However, severe alcohol-associated hepatitis and cirrhosis are irreversible.

• Second most common cause of liver cirrhosis in the United States
• 28% of the US population exceeds the recommended limits of alcohol consumption.
• Lifetime prevalence of alcohol use disorder: 18%
• ∼ 10–20% of heavy drinkers develop cirrhosis.

References:^[6][7][8]

Epidemiological data refers to the US, unless otherwise specified.

Alcohol-related risk factors ^[2][3]

• Alcohol use disorder
• Harmful alcohol use, especially if consumed from a young age and for individuals in their 40s or 50s
  • Men: ≥ 3 drinks per day or ≥ 21 per week
  • Women: ≥ 2 drinks per day or ≥ 14 per week
• Binge drinking
• Drinking outside of meal times
• Drinking daily
• See “Classifications of alcohol use” for definitions and types of alcohol consumption.

Non-alcohol-related risk factors ^[2][3]

• Obesity
• MASLD
• Hepatitis B
• Hepatitis C
• Tobacco use
• Female sex
• Hispanic or Native American descent
• Low socioeconomic status
• Certain genetic variants

Coffee consumption may reduce the risk of ALD in individuals with heavy alcohol use. ^[3]

• Hepatic degradation of ethanol to acetyl-CoA by alcohol dehydrogenase results in NADH excess (see breakdown of ethanol for more details) → ↑ NADH drives the formation of glycerol 3-phosphate (G3P) from dihydroxyacetone phosphate (DHAP) → ↑ in both G3P and fatty acids causes increased triglyceride synthesis in the liver and accompanying inflammation → steatohepatitis → chronic inflammation leads to hepatic fibrosis and sclerosis → portal hypertension and eventually cirrhosis

See “Diagnostics for cirrhosis” and “Diagnosis of alcohol-associated hepatitis” for more detailed approaches to those manifestations of ALD.

Approach ^[2][3]

• Screen individuals with harmful alcohol use for ALD using laboratory studies and liver ultrasound.
• ALD diagnosis requires:
  • ≥ 12 months of harmful alcohol use
  • Typical clinical, laboratory, and/or imaging findings of liver disease
  • Exclusion of alternative causes of liver disease (e.g., viral hepatitis, autoimmune hepatitis, hemochromatosis)
• In individuals with asymptomatic ALD, evaluate the severity of liver fibrosis using noninvasive tests.

Laboratory studies ^[2][3]

• Early ALD
  • Elevated transaminases
    • ↑ ALT and ↑ AST (typically < 400 U/L) ^[3]
    • AST > ALT
  • ↑ Alkaline phosphatase
  • Macrocytic anemia ^[9]
  • ↑ Serum ferritin ^[10]
• Advanced ALD
  • ↑ Bilirubin
  • ↑ PT and INR
  • ↓ Albumin
  • Thrombocytopenia
• Direct alcohol biomarkers ^[2]
  • Blood alcohol concentration
  • Urine and/or hair ethyl glucuronide
  • Urine ethyl sulfate
  • Blood phosphatidylethanol
• Indirect alcohol biomarkers
  • ↑ GGT
    • Indicates alcohol-induced tissue damage
    • Highly variable and low sensitivity ^[2]
  • ↑ Carbohydrate-deficient transferrin: low sensitivity and may be falsely positive in individuals with severe liver disease but no alcohol use

Imaging ^[11]

• Ultrasound: first line
  • Mild hepatomegaly
  • Blood vessels cannot be visualized.
  • ↑ Liver echogenicity due to steatosis; may be focal or diffuse
• CT: ↓ liver attenuation

Imaging findings and laboratory study results will return to normal within weeks of cessation of alcohol consumption in patients with alcohol-associated steatosis. ^[12]

Screening for fibrosis ^[2][3]

Screen individuals with asymptomatic ALD and consider screening individuals with heavy alcohol use.

• Noninvasive tests: preferred screening method
  • FIB-4 score
  • Transient elastography
• Liver biopsy: if there is diagnostic uncertainty after noninvasive tests

• Immediate cessation of alcohol consumption
• Multidisciplinary management of AUD
• Hepatology referral for individuals with advanced liver fibrosis or cirrhosis
• Treatment of alcohol-associated hepatitis and treatment of cirrhosis as indicated
• Liver transplant evaluation for patients with severe disease

Decompensated cirrhosis

Mainly characterized by a constellation of clinical features resulting from decreased hepatic function:

• Portal hypertension
• Ascites
• Hepatic encephalopathy
• Coagulopathy
• Hepatorenal syndrome
• Hyperestrogenism
• End-stage liver disease

Other organ damage following chronic alcohol use

• Gastritis
• Malabsorption
• Chronic pancreatitis
• Wernicke-Korsakoff syndrome
• See “Alcohol use disorder.”

Zieve syndrome ^[13]

• A rare condition that can occur in individuals with ALD
• Characterized by the following triad:
  • Hemolytic anemia
  • Jaundice
  • Hyperlipidemia

We list the most important complications. The selection is not exhaustive.