What are the causes of cirrhosis?

Causes of Cirrhosis

The three main causes of cirrhosis are chronic alcohol consumption, chronic viral hepatitis (B and C), and non-alcoholic fatty liver disease (NAFLD), which together account for approximately 90% of all cases worldwide. 1

Major Etiologies

1. Viral Hepatitis

• Hepatitis B: Accounts for approximately 60% of HCC cases in Africa and East Asia, but only 20% in Western countries 2
• Hepatitis C: Major risk factor in Western countries, responsible for 31% of cases globally 2
• Risk of progression to cirrhosis:
  • HBV: 2% per year in cirrhotic patients 2
  • HCV: 3-8% per year in cirrhotic patients 2
  • Risk factors for progression: HBeAg seropositivity, high viral load, genotype C (for HBV) 2

2. Alcohol-Related Liver Disease

• Most common cause of cirrhosis in many Western countries, accounting for 40% of cirrhosis deaths in the United States 2
• Contributes to 32-53% of HCC cases depending on geographic region 2
• Progression depends on amount and duration of alcohol consumption
• Often coexists with other liver diseases, particularly hepatitis C

3. Non-Alcoholic Fatty Liver Disease (NAFLD)

• Emerging as a leading cause of cirrhosis due to increasing prevalence of obesity and metabolic syndrome 2
• Prevalence of hepatic steatosis in US population: 21.4% 2
• NAFLD can progress to non-alcoholic steatohepatitis (NASH) and eventually cirrhosis
• Risk factors: obesity, diabetes, metabolic syndrome

Less Common Causes

4. Genetic/Metabolic Disorders

• Hemochromatosis: Up to 45% of patients develop HCC, usually with underlying cirrhosis 2
• Alpha-1-antitrypsin deficiency: Well-documented complication of cirrhosis 2
• Wilson's disease: HCC develops occasionally, but only in the presence of cirrhosis 2

5. Autoimmune Liver Diseases

• Autoimmune hepatitis: Can progress to cirrhosis despite immunosuppressive therapy 2
• Primary biliary cirrhosis: Incidence of HCC similar to hepatitis C-related cirrhosis 2
• Primary sclerosing cholangitis: Can lead to cirrhosis and increased risk of cholangiocarcinoma

6. Environmental/Toxic Exposures

• Aflatoxin B1: Important co-factor for HCC development in parts of Africa and Asia 2
• Drug-induced liver injury: Various medications can cause chronic liver damage leading to cirrhosis
• Industrial toxins: Prolonged exposure to certain chemicals can cause liver fibrosis

7. Cryptogenic Cirrhosis

• Accounts for 3-30% of cirrhosis cases 2
• Often represents "burnt-out" NASH, silent autoimmune hepatitis, or occult viral infection 2
• Classification schemes based on residual histological findings (autoimmune-like inflammatory infiltrates vs. NASH-like foci) 2

Risk Factors for Disease Progression

• Age and gender: Older age and male gender correlate with HCC development 2
• Portal hypertension: Liver cancer incidence increases with portal pressure 2
• Liver stiffness: Higher degree of liver stiffness (measured by transient elastography) correlates with increased risk 2
• Comorbidities: HIV co-infection accelerates progression of viral hepatitis 2
• Obesity and diabetes: Independent risk factors for progression of liver disease 2

Clinical Implications

• Early identification of underlying cause is crucial as some etiologies (viral hepatitis, alcohol, NAFLD) may be reversible with appropriate intervention 3
• Patients with cirrhosis should undergo regular surveillance for hepatocellular carcinoma with imaging studies every 6-12 months 4
• The prognosis depends on disease stage, presence of portal hypertension, development of complications, and prognostic scores (Child-Pugh, MELD) 1

Understanding the specific etiology of cirrhosis is essential for appropriate management, as treatment directed at the underlying cause may slow or halt disease progression and potentially reverse early cirrhosis.