What are the primary causes of liver cirrhosis in adults?

Primary Causes of Liver Cirrhosis in Adults

The primary causes of liver cirrhosis vary by geographic region, but globally include chronic viral hepatitis (hepatitis B and C), alcohol-related liver disease (ARLD), and metabolic dysfunction-associated steatotic liver disease (MASLD), with viral hepatitis accounting for approximately 78% of cirrhosis cases worldwide, while in Western countries like the UK and US, ARLD and MASLD predominate. 1

Global Epidemiology

Viral hepatitis remains the leading cause worldwide:

• Hepatitis B and C viruses account for approximately 57% of cirrhosis cases globally 1
• HBV and HCV affect an estimated 400 million and 170 million people respectively, representing risk factors in over 80% of cases globally 2
• Chronic HBV infection carries a 15-25% risk of premature death from liver cancer or end-stage liver disease 1

Geographic distribution patterns:

• Chronic HCV infection is the most common underlying cause in North America, Europe, and Japan 2
• Chronic HBV infection is the major cause in Asia and Africa, and approximately 20% of cases in Western countries 2
• HBV can cause cirrhosis even without established fibrosis through insertional mutagenesis into the host genome 2, 1

Western Countries (UK, US, Europe)

ARLD and MASLD are the dominant causes in Western populations:

• In the UK, ARLD and MASLD are more common than viral hepatitis 2
• ARLD and MASLD account for nearly 70% of cirrhosis cases in northern England 2, 1
• Alcohol excess causes approximately 36% of liver cancers 2, 1

Alcohol-related liver disease specifics:

• The estimated incidence of complications in patients with alcohol-related cirrhosis is 2.9 per 100 patient-years 2
• In some European countries, alcohol accounts for 40-50% of cirrhosis cases 3
• Chronic alcohol abuse leads to direct hepatotoxicity from ethanol metabolites and increased intestinal permeability, allowing bacterial translocation that generates a strong pro-inflammatory response 4

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

MASLD is an increasingly important cause:

• MASLD affects up to one in five people (approximately 19% of adults) in the United Kingdom and Western nations 1, 3
• MASLD-associated cirrhosis contributes 10-14% of cases in Western countries 2, 1
• The risk of developing cirrhosis in MASLD-related chronic liver disease is between 18-27%, which exceeds the risk in HCV-related disease 1
• MASLD-related cirrhosis increased 10-20 fold between 2004 and 2010 in regions with lower viral hepatitis prevalence 2

Key metabolic risk factors:

• The combination of insulin resistance, hypertension, dyslipidemia, and obesity (metabolic syndrome) is recognized as a cause of cirrhosis 1
• Both obesity and type 2 diabetes mellitus independently increase risk beyond causing chronic liver disease 2
• Over 60% of patients with cirrhosis have features of metabolic syndrome, regardless of underlying etiology 2

Other Significant Causes

Autoimmune and cholestatic diseases:

• Primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis all increase cirrhosis risk 2, 1, 3
• Approximately one-third of adult patients with autoimmune hepatitis have cirrhosis at presentation 1

Genetic and hereditary conditions:

• Hemochromatosis carries a 200-fold increased relative risk of cirrhosis compared to the normal population 1
• Hereditary hemochromatosis can lead to cirrhosis in up to 45% of cases 3
• Wilson disease can progress to cirrhosis if untreated 1
• Alpha-1-antitrypsin deficiency is a well-documented cause 3

Cryptogenic cirrhosis:

• Found in 3-30% of patients with cirrhosis 1
• NASH is considered one of the leading causes of cryptogenic cirrhosis in Western countries, based on serial biopsy reports demonstrating progression of prior NASH to cirrhosis without continuing definitive evidence of NASH 1
• Other putative causes include silent or "burnt out" autoimmune hepatitis, occult viral infection, and covert alcoholism 1

Common Pitfalls in Clinical Practice

Important considerations when evaluating cirrhosis etiology:

• Pre-existing liver disease significantly increases the risk of progression, and steatosis leads to impaired hepatic microcirculation 1
• Neoadjuvant chemotherapy, particularly oxaliplatin and irinotecan, can be hepatotoxic and increase risk 1
• Cholestasis can significantly increase morbidity (50% vs 15%) and mortality (5-13% vs 0-6%) compared to patients without cholestasis 1
• Approximately 20% of cases occur in non-cirrhotic livers, including patients with chronic liver disease but not cirrhosis secondary to HBV and MASLD 2, 1

Risk stratification factors:

• More than 90% of cases occur in the context of chronic liver disease 2
• Men are between three and five times more likely to develop complications than women, regardless of underlying etiology 2
• Increasing age is an associated risk factor, with peak incidence in people over 80 years 2
• People living in more deprived areas are up to five times more likely to die of liver disease 2