What are the primary causes and management options for liver cirrhosis?

Causes of Liver Cirrhosis

Primary Etiologies

The most common causes of liver cirrhosis globally are chronic viral hepatitis (hepatitis B and C), alcohol-related liver disease, and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), with the relative prevalence varying by geographic region. 1

Viral Hepatitis

• Hepatitis B and C viruses account for approximately 78% of hepatocellular carcinoma cases and 57% of cirrhosis cases worldwide, making them the leading global causes 1
• Hepatitis C is the most common underlying liver disease among patients with cirrhosis in North America, Europe, and Japan, primarily affecting those with cirrhosis or bridging fibrosis 1
• Hepatitis B is the major cause of cirrhosis in Asia and Africa and approximately 20% of cases in Western countries 1
• HBV can cause cirrhosis even without established cirrhosis through insertional mutagenesis, though most HBV-associated cirrhosis occurs in patients with underlying cirrhosis 1
• In the UK, HBV prevalence is 0.1-0.5% and HCV affects 0.5-1% of the population 1

Alcohol-Related Liver Disease (ARLD)

• Alcohol excess causes approximately 36% of liver cancers and is a leading cause of cirrhosis in Western countries 1
• In England and Scotland, alcohol is the predominant cause, with ARLD accounting for nearly 70% of cirrhosis cases in northern England 1
• The estimated incidence of hepatocellular carcinoma in patients with alcohol-related cirrhosis is 2.9 per 100 patient-years 1
• In some European countries, alcohol accounts for 40-50% of cirrhosis cases 2

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• MASLD affects up to one in five people (approximately 19% of adults) in the United Kingdom and Western nations 1, 2
• MASLD-associated cirrhosis contributes 10-14% of cirrhosis cases in Western countries 1
• In the UK northeast region, MASLD-related cirrhosis increased 10-20 fold between 2004 and 2010 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
• Over 60% of patients with cirrhosis have features of metabolic syndrome, regardless of underlying etiology 1

Other Significant Causes

• Hemochromatosis carries a 200-fold increased relative risk of cirrhosis compared to the normal population 1
• Primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis all increase cirrhosis risk 1
• Alpha-1-antitrypsin deficiency is a well-documented genetic cause 2
• Approximately one-third of cirrhotic patients will develop liver cancer during their lifetime 1

Geographic and Demographic Variations

United States

• Alcohol use disorder accounts for approximately 45% of cirrhosis cases 3
• MASLD accounts for 26% of cases 3
• Hepatitis C accounts for 41% of cases (with overlap between etiologies) 3

United Kingdom

• ARLD and MASLD are more common than viral hepatitis 1
• Nearly 70% of cirrhosis cases in northern England are due to ARLD and MASLD combined 1

Non-Cirrhotic Liver Disease Leading to Complications

• Approximately 20% of hepatocellular carcinoma cases occur in non-cirrhotic livers 1
• This includes patients with chronic liver disease but not cirrhosis secondary to HBV and MASLD 1
• Acute hepatic porphyrias and malignant transformation of adenomas can also lead to complications without cirrhosis 1

Clinical Implications

• An estimated 78% of cirrhosis cases are caused by chronic HBV or HCV infection globally 1
• Chronic HBV infection carries a 15-25% risk of premature death from liver cancer or end-stage liver disease 1
• Approximately 600,000 people die worldwide annually from HBV-related liver disease or hepatocellular carcinoma 1
• The incidence of cirrhosis in the United States tripled from 1975 through 2005, largely due to HCV-related disease 1
• From 2010 to 2021, annual age-adjusted mortality from cirrhosis increased from 14.9 to 21.9 per 100,000 people in the US 3