From the Guidelines
Cirrhosis is primarily caused by chronic liver damage from several conditions, with alcoholic liver disease, viral hepatitis, and nonalcoholic fatty liver disease (NAFLD) being the most common causes worldwide, as supported by the most recent study 1. The causes of cirrhosis can be broken down into several key categories:
- Alcoholic liver disease: Excessive alcohol consumption over many years damages liver cells and leads to inflammation and scarring, as noted in 1.
- Viral hepatitis: Chronic infections with hepatitis B and C viruses directly attack liver cells, causing progressive damage, with hepatitis B and C affecting an estimated 400 million and 170 million people, respectively, and being the risk factors in over 80% of HCC cases globally 1.
- Nonalcoholic fatty liver disease (NAFLD): Particularly its more severe form nonalcoholic steatohepatitis (NASH), has become a leading cause of cirrhosis due to increasing obesity rates, with NAFLD-associated HCC becoming a relevant cause of HCC in developed regions 1. Other significant causes include:
- Autoimmune hepatitis: Where the immune system attacks liver cells.
- Inherited disorders: Such as hemochromatosis (iron overload), Wilson's disease (copper accumulation), and alpha-1 antitrypsin deficiency.
- Biliary diseases: That block bile ducts, such as primary biliary cholangitis and primary sclerosing cholangitis.
- Certain medications or toxins: With prolonged exposure, which can all lead to persistent inflammation and liver cell death, triggering a repair process that results in fibrosis (scarring) and eventually the nodular, dysfunctional liver architecture characteristic of cirrhosis, as discussed in 1. Additionally, dietary factors, such as a high intake of sugars, refined carbohydrates, and saturated fats, have been linked to an increased risk of cirrhosis, while a Mediterranean-style diet rich in vegetables, whole grains, fruits, seafood, and olive oil may improve liver function and reduce the risk of abnormalities, as suggested by 1. It's essential to consider these factors when assessing the risk of cirrhosis and implementing preventive measures, as the risk of HCC development is higher in patients with chronic viral hepatitis, and approximately one-third of cirrhotic patients will develop HCC during their lifetime 1.
From the Research
Primary Causes of Cirrhosis
The primary causes of cirrhosis can be classified into several categories, including:
- Alcoholic liver disease (ALD) 2
- Chronic hepatitis C virus (HCV) infection 2
- Nonalcoholic fatty liver disease (NAFLD) 3, 2, 4
- Hepatoviruses, which can cause hepatocellular necrosis and initiate the inflammatory process leading to cirrhosis 5
Risk Factors and Clinical Presentation
The risk factors and clinical presentation of cirrhosis vary depending on the underlying cause. For example:
- ALD patients tend to be younger and have worse liver function than HCV and NAFLD patients 2
- NAFLD patients often have a history of obesity, diabetes, and metabolic syndrome 3, 4
- HCV patients may have a higher risk of developing hepatocellular carcinoma (HCC) than ALD and NAFLD patients 2
Diagnosis and Management
The diagnosis and management of cirrhosis also depend on the underlying cause. For example:
- Liver biopsy is often required for definitive diagnosis of cirrhosis 5
- Non-invasive liver function testing and imaging modalities can be used to diagnose and stage hepatic fibrosis 4
- Treatment options include targeted medical therapy, surgical or endoscopic intervention, and liver transplantation 6, 4