What is the leading cause of liver failure in adults?

Leading Cause of Liver Failure in Adults

Alcohol-related liver disease is the leading cause of chronic liver failure and cirrhosis-related mortality in Western countries, while acetaminophen overdose is the most common cause of acute liver failure. 1, 2

Context Matters: Acute vs. Chronic Liver Failure

The leading cause depends critically on whether you're addressing acute or chronic liver failure:

Acute Liver Failure (ALF)

Acetaminophen (paracetamol) overdose is the most common cause of acute liver failure in Western countries, including the United States and Europe. 2, 3

• Drug-induced hepatotoxicity beyond acetaminophen—including antimicrobials, antiepileptics, and statins—represents another major contributor to ALF 2
• Viral hepatitis (particularly hepatitis A, B, and E) causes significant ALF, with hepatitis E being especially severe in pregnant women 2
• Geographic variation is substantial: in developing countries in Asia and Africa, viral hepatitis B and E predominate as ALF causes, whereas Western nations see more drug-related cases 3

Chronic Liver Failure and Cirrhosis

Alcohol use disorder is the leading cause of chronic liver failure and cirrhosis in Western countries, accounting for approximately 45% of all cirrhosis cases and representing the primary cause of liver-related mortality. 1, 2, 4

• In France specifically, alcohol is explicitly identified as the leading cause of liver diseases and liver-related mortality 1
• Alcohol-related liver disease accounts for 40-50% of all liver transplants in high-income countries 4
• In 2017, more than 2 million people in the United States had alcohol-associated cirrhosis 4

The "Big Three" Causes of Chronic Liver Disease

Beyond the leading cause, the burden of chronic liver disease reflects three major etiologies: 1

1. Alcohol-related liver disease (ARLD) - the predominant cause
2. Non-alcoholic fatty liver disease (NAFLD) - now recognized as the leading cause of chronic liver disease globally (though not necessarily of liver failure), affecting approximately 25% of adults worldwide 1
3. Viral hepatitis (hepatitis B and C) - with hepatitis C accounting for 41% of some cirrhosis cohorts 2

Critical Clinical Distinctions

The distinction between NAFLD as the most common chronic liver disease versus alcohol as the leading cause of liver failure and mortality is crucial. 1, 4

• NAFLD affects 1 in 4 adults globally, but many cases remain non-progressive 1
• Alcohol-related cirrhosis carries higher mortality risk and accounts for approximately 27% of 1.32 million cirrhosis deaths worldwide in 2017 4
• Metabolic dysfunction-associated fatty liver disease (MAFLD) is growing as a cause of cirrhosis, accounting for 26% of cases in some cohorts 2

Common Pitfalls to Avoid

Do not overlook alcohol consumption when evaluating liver disease. 1

• Failing to quantitatively assess alcohol intake leads to misclassification between NAFLD and alcohol-related disease 5
• Use validated screening tools like AUDIT scores; scores >19 indicate alcohol dependency requiring referral to alcohol services 1
• Many patients with NAFLD also have concurrent harmful alcohol use (the "MetALD" overlap), consuming 20-50g/day in women or 30-60g/day in men 5

In acute presentations, always consider acetaminophen toxicity first in Western populations, as specific antidotal therapy (N-acetylcysteine) is available and time-sensitive. 2, 3

Geographic and Demographic Variations

The etiology hierarchy shifts based on location: 3

• Western countries: Acetaminophen (ALF), alcohol (chronic failure)
• Asia/Africa: Viral hepatitis B and E predominate
• Emerging trend: NAFLD/MAFLD is projected to become an increasingly dominant cause as obesity and type 2 diabetes prevalence rises globally 1, 2