What are the primary causes of cirrhosis (scarring of the liver)?

Primary Causes of Cirrhosis (Liver Scarring)

The primary causes of cirrhosis are chronic viral hepatitis (hepatitis B and C), alcohol-related liver disease, and metabolic-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease), which together account for approximately 85% of all cirrhosis cases worldwide. 1, 2

Viral Hepatitis

• Hepatitis B virus (HBV) accounts for approximately 54% of cirrhosis cases globally, with the highest prevalence in Africa and East Asia 1
• Hepatitis C virus (HCV) causes approximately 31% of cirrhosis cases worldwide and is the leading cause in North America and Western countries 1
• Risk factors for progression to cirrhosis in HBV include HBeAg seropositivity, high viral load, and genotype C 1
• HCV genotypes 1b and 3 are associated with increased risk of progression to cirrhosis and hepatocellular carcinoma 1

Alcohol-Related Liver Disease

• Chronic alcohol abuse is a major cause of cirrhosis globally, accounting for 32-53% of cases depending on geographical region 1
• In some European countries, alcohol accounts for 40-50% of cirrhosis cases 2
• In the United States, alcohol-related liver disease accounts for approximately 45% of all cirrhosis cases 3
• The risk of developing hepatocellular carcinoma in patients with alcohol-related cirrhosis is estimated at 2.9 per 100 patient-years 1

Metabolic Causes

• Metabolic-associated steatotic liver disease (MASLD) is an increasingly recognized cause of cirrhosis 1, 2
• MASLD affects approximately 19% of US adults, corresponding to an estimated 28.8 million people 2
• MASLD-associated hepatocellular carcinoma accounts for 10-14% of cases in Western countries 1
• Risk factors include obesity, diabetes, insulin resistance, hypertension, and dyslipidemia (collectively known as metabolic syndrome) 1, 2
• The risk of developing hepatocellular carcinoma in MASLD-related chronic liver disease is between 18-27%, potentially higher than in HCV-related cirrhosis 1

Other Causes

• Hereditary hemochromatosis can lead to cirrhosis in up to 45% of cases, with a relative risk of hepatocellular carcinoma 200 times that of the normal population 1, 2
• Alpha-1-antitrypsin deficiency is a well-documented genetic cause of cirrhosis 1, 2
• Autoimmune liver diseases including primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis can progress to cirrhosis 1, 2
• Acute hepatic porphyrias and porphyria cutanea tarda increase the risk of cirrhosis and hepatocellular carcinoma 1

Geographical Variations

• In Asia and Africa, HBV is the predominant cause (41% in East Asia) 1
• In Western Europe and North America, HCV and alcohol are the leading causes 1
• In the UK, alcohol-related liver disease and MASLD account for nearly 70% of hepatocellular carcinoma cases 1
• Regional variations exist even within countries; for example, in northern England where viral hepatitis is less prevalent, MASLD-related hepatocellular carcinoma increased 10-20 fold between 2004 and 2010 1

Disease Progression

• Approximately one-third of cirrhotic patients will develop hepatocellular carcinoma during their lifetime 1
• The annual incidence of hepatocellular carcinoma in cirrhotic patients ranges from 1-8%, with higher rates in HCV-related cirrhosis (3-8%) compared to HBV-related cirrhosis (2%) 1
• In approximately 20% of cases, hepatocellular carcinoma can occur in a non-cirrhotic liver, particularly in patients with HBV, MASLD, or acute hepatic porphyrias 1

Understanding the etiology of cirrhosis is crucial for implementing appropriate preventive strategies, including HBV vaccination, HCV treatment, alcohol cessation, and management of metabolic syndrome to reduce the global burden of this disease 1, 2.