Alcoholic liver disease

Alcoholic liver disease (ALD) refers to a range of progressive liver conditions caused by chronic and excessive alcohol consumption. One-third of the US population consumes alcohol above the recommended levels, increasing their risk of ALD. There are three stages of ALD, which may or may not occur sequentially. The first stage is typically asymptomatic and involves the development of (potentially) reversible alcoholic fatty liver. Continued alcohol consumption will lead to alcoholic hepatitis, the second stage, which often becomes chronic. Clinical findings in this stage include jaundice, fatigue, and fever. In the third and final stage, the patient develops alcoholic cirrhosis. Patient history, transaminase levels, and imaging studies are crucial for diagnosis and show different patterns of hepatic injury. Nonalcoholic steatohepatitis is a differential diagnosis and is currently regarded as an important cause of cirrhosis. Treatment of ALD requires complete cessation of alcohol use.

The management of alcoholic hepatitis, including its diagnosis and treatment, is described in detail elsewhere.

• 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 abuse: 18%
• ∼ 10–20% of heavy drinkers develop cirrhosis.

References:^[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

• Alcoholism is a very important cause of chronic liver diseases.
• Significant alcohol consumption
  • Men: > 210 g pure alcohol per week
  • Women: > 140 g pure alcohol per week

References:^[4]

• 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

The stages of ALD may overlap and do not necessarily occur in sequence.

Alcoholic fatty liver (reversible)

• Mostly asymptomatic
• Some patients report feeling a sensation of pressure in the upper abdominal area.
• Hepatomegaly: soft in consistency
• Regresses after cessation of alcohol consumption
• Acute exacerbation with risk of hepatic failure is rare.

Alcoholic hepatitis (reversible in mild cases)

See “Alcoholic hepatitis.”

Alcohol-related cirrhosis (irreversible)

• Final stage of ALD
• See “Clinical features” in cirrhosis.

References:^[5]

A history of alcohol abuse that correlates with typical laboratory and imaging findings is diagnostic of alcoholic liver disease.

Alcoholic fatty liver

• Laboratory tests
  • AST (aspartate aminotransferase) > ALT (alanine aminotransferase) (both ↑ ALT and ↑ AST)
  • ↑ GGT
  • ↑ Serum ferritin
  • Macrocytic anemia ^[6]
  • ↑ CDT(carbohydrate-deficient transferrin)
    • Most specific biomarker of heavy alcohol use regardless of the presence of liver disease
    • Levels elevated up to 6 weeks after abuse
• Imaging
  • Ultrasound
    • Mild hepatomegaly
    • Blood vessels cannot be visualized
    • ↑ Liver echogenicity because of steatosis: may be focal or diffuse
  • CT: ↓ liver attenuation

Imaging and laboratory studies in the case of alcoholic fatty liver will show a reversal of changes within a month if the patient abstains from alcohol.

Alcoholic hepatitis

See “Alcoholic hepatitis.”

Alcohol-related cirrhosis

• See cirrhosis.
• Diagnosis confirmed by biopsy

References:^[7]

• Alcoholic fatty liver: accumulation of lipid droplets in the hepatocytes with gradual single cell necrosis within the lobules
• Alcoholic hepatitis
  • Macrovesicular steatosis with hydropic swelling and ballooning degeneration of hepatocytes within the lobules
  • Damaged hepatocytes typically contain Mallory-Denk bodies (hyaline inclusion bodies that contain keratin filaments and appear eosinophilic on HE staining).
  • Immunoreaction: neutrophilic granulocytes within hepatic tissue
  • Pericellular and sinusoidal fibrosis
    • Pronounced excess formation of fibrous collagenous connective tissue
    • Pattern of chicken wire-like network in perivenous zones
    • Mechanical obstruction of the bile ducts and biliary stasis
• Alcohol-related cirrhosis
  • Infiltration of lymphocytes
  • Massive accumulation of fat in hepatocytes
  • Formation of fibrous septa and regenerative nodules
  • Perivascular sclerosis of central veins (especially in the early stage)

Alcoholic fatty liver and mild alcoholic hepatitis may be reversible after cessation of alcohol intake. However, severe alcoholic hepatitis and cirrhosis are not reversible!

References:^[8][9][10]

• Immediate cessation of alcohol use
• In some cases, glucocorticoids (e.g., prednisolone)

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

• Acute hemolytic anemia after excessive alcohol use over the course of several years, characterized by the following triad:
  • Alcoholic hepatitis
  • Jaundice
  • Hyperlipidemia

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