From the Guidelines
Fatty liver can cause cirrhosis through a progressive process of liver damage, as evidenced by the most recent guidelines from the EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) 1. When fat accumulates in liver cells (steatosis), it triggers inflammation and oxidative stress, leading to cell injury. Over time, this chronic inflammation causes fibrosis, where healthy liver tissue is replaced by scar tissue. As fibrosis advances, the liver's architecture becomes distorted, blood flow is impaired, and liver function deteriorates, resulting in cirrhosis. This progression is particularly common in conditions like non-alcoholic steatohepatitis (NASH) and alcoholic liver disease. The risk of developing cirrhosis increases with obesity, diabetes, excessive alcohol consumption, and genetic factors. Some key points to consider in the management of fatty liver disease include:
- The importance of lifestyle modification, including weight loss, dietary changes, physical exercise, and discouraging alcohol consumption, as advised in the EASL-EASD-EASO guidelines 1.
- The use of non-invasive tests, such as the fibrosis-4 index (FIB-4) and transient elastography, to rule out advanced fibrosis, which is predictive of liver-related outcomes 1.
- The consideration of MASH-targeted treatment with resmetirom in adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2), as recommended in the EASL-EASD-EASO guidelines 1.
- The management of MASH-related cirrhosis, including adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, and liver transplantation in decompensated cirrhosis, as outlined in the EASL-EASD-EASO guidelines 1. The process typically takes years or decades, and early stages are often reversible with lifestyle changes, including weight loss, exercise, diabetes management, and alcohol abstinence. However, once cirrhosis develops, the damage becomes irreversible, though further progression can be slowed with appropriate management of the underlying cause, as emphasized in the quality standards for the management of non-alcoholic fatty liver disease (NAFLD) 1.
From the Research
Fatty Liver and Cirrhosis
- Fatty liver disease, also known as non-alcoholic fatty liver disease (NAFLD), can lead to cirrhosis, a condition characterized by scarring of the liver tissue 2, 3.
- NAFLD encompasses a disease continuum from steatosis with or without mild inflammation to non-alcoholic steatohepatitis (NASH), which is characterized by necroinflammation and faster fibrosis progression than non-alcoholic fatty liver 3.
- The development of cirrhosis in NAFLD is a result of chronic inflammation, which leads to the activation of hepatic stellate cells and the formation of liver fibrosis 4.
Mechanisms of Cirrhosis Development
- Chronic inflammation in the liver leads to a cascade of events, including the activation of hepatic stellate cells, which undergo trans-differentiation to become myofibroblasts, the main extra-cellular matrix producing cells in the liver 4.
- Sustained chronic fibrosis can become pathogenic, culminating in cirrhosis and its associated complications, such as portal hypertension, systemic inflammation, and liver failure 2, 5.
- The progression of NAFLD to cirrhosis can be influenced by various factors, including obesity, type 2 diabetes, and metabolic syndrome 3, 6.
Diagnosis and Management
- The diagnosis of cirrhosis typically involves a combination of non-invasive tests, including laboratory tests, imaging, and scoring indices, as well as liver biopsy in some cases 5, 6.
- Management of cirrhosis is centered on the treatment of the underlying cause, such as NAFLD, and the prevention of complications, including hepatocellular carcinoma, ascites, and variceal bleeding 2, 5.
- Liver transplantation may be required in some cases, particularly for patients with advanced cirrhosis and significant liver dysfunction 2, 5.