Can Non-Alcoholic Steatohepatitis (NASH) or Non-Alcoholic Fatty Liver Disease (NAFLD) cause fibrosis or cirrhosis?

From the Guidelines

Yes, both NASH (Non-alcoholic Steatohepatitis) and NAFLD (Non-alcoholic Fatty Liver Disease) can cause fibrosis and potentially progress to cirrhosis. NAFLD represents a spectrum of liver conditions, with simple steatosis (fatty liver) being the mildest form. When inflammation and liver cell damage occur alongside fat accumulation, it becomes NASH, which is the more aggressive form of NAFLD. NASH can lead to progressive liver fibrosis, where healthy liver tissue is replaced by scar tissue. If fibrosis continues unchecked, it can eventually develop into cirrhosis, characterized by extensive scarring that impairs liver function.

Key Points

• The progression from NAFLD to NASH to fibrosis to cirrhosis typically occurs over many years.
• Risk factors that accelerate this progression include obesity, type 2 diabetes, metabolic syndrome, and genetic predisposition.
• Management focuses on lifestyle modifications including weight loss through diet and exercise, controlling diabetes and other metabolic conditions, and avoiding alcohol.
• Currently, there are no FDA-approved medications specifically for NASH, though several are in clinical trials.
• Regular monitoring with liver function tests and imaging is important for patients with NAFLD/NASH to track potential progression to more severe liver disease, as supported by recent studies 1, 2, 3.

Risk Stratification

• Patients with T2D, 2 or more metabolic risk factors, or incidental finding of hepatic steatosis or elevated aminotransferases are at higher risk for NAFLD-related fibrosis and should be screened accordingly 3.
• The NAFLD fibrosis score or Fibrosis-4 Index can be used to rule out advanced fibrosis in these high-risk patients.
• Further assessment with elastography or serum marker tests may be necessary for patients at intermediate or high risk of fibrosis.

Conclusion Not Applicable - Outcome Focus

The focus is on the outcome of Morbidity, Mortality, and Quality of Life, thus the key is to identify and manage NAFLD and NASH early to prevent progression to fibrosis and cirrhosis, as the risk of liver-related mortality increases exponentially with each increase in fibrosis stage, from an RR of 1.41 for stage 1 to an RR of 42.30 for stage 4 fibrosis 1.

From the Research

NAFLD and NASH-Related Fibrosis and Cirrhosis

• Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) can lead to liver fibrosis and cirrhosis 4, 5, 6, 7.
• NASH is a more aggressive form of NAFLD and can progress to hepatic fibrosis, cirrhosis, portal hypertension, and primary liver cancer 6.
• The disease continuum of NAFLD encompasses steatosis with or without mild inflammation, to NASH, which is characterized by necroinflammation and faster fibrosis progression than non-alcoholic fatty liver 7.

Mechanisms and Treatment of Fibrosis

• Liver fibrosis is the excessive expression and accumulation of extracellular matrix proteins in the liver, occurring as a consequence of chronic injury and inflammation 5.
• Treatment options for NAFLD and NASH are limited, but several drugs are being investigated, including pioglitazone, vitamin E, and statins 4, 6, 8.
• Lifestyle modifications, such as weight loss, exercise, and a healthy diet, are the basis for prevention and treatment of NAFLD-associated fibrosis 5, 7.

Prevention and Management

• Preventive strategies are necessary to avoid complications of fibrosis, particularly cirrhosis, portal hypertension, and liver cancer 5.
• Combination treatment is likely to be required for many patients with NAFLD due to the complex pathophysiology and substantial heterogeneity of disease phenotypes 7.
• Healthy lifestyle and weight reduction remain crucial to the prevention and treatment of NAFLD 7.