What is NASH?
NASH (non-alcoholic steatohepatitis) is a progressive inflammatory form of fatty liver disease defined by the presence of ≥5% hepatic steatosis plus inflammation with hepatocyte injury (ballooning), with or without fibrosis, occurring in the absence of significant alcohol consumption. 1
Key Defining Features
NASH represents the more severe end of the NAFLD spectrum and is distinguished from simple fatty liver (NAFL) by three critical histologic components:
- ≥5% hepatic steatosis (fat accumulation in liver cells)
- Hepatocyte ballooning (enlargement and injury of liver cells)
- Lobular inflammation (inflammatory cell infiltration)
- Variable fibrosis (may or may not be present) 1
Clinical Significance and Prognosis
NASH can progress to cirrhosis, liver failure, and hepatocellular carcinoma, making it fundamentally different from simple steatosis which carries minimal risk of progression. 1 Approximately 20% of patients with NASH will develop cirrhosis 2, and NASH is predicted to become the leading indication for liver transplantation in the United States.
The mortality implications are substantial:
- All-cause mortality rate: 25.56 per 1,000 person-years
- Liver-specific mortality rate: 11.77 per 1,000 person-years 2
These rates are substantially higher than the general population or patients with simple steatosis.
Metabolic Context
NASH occurs within the broader context of metabolic dysfunction and is strongly associated with:
The disease affects an estimated 3-6% of the US population 2, though within the broader NAFLD population (affecting ~25% globally), NASH prevalence among those undergoing liver biopsy ranges from 6.67% to 29.8% 1.
Diagnostic Requirements
Liver biopsy remains the only accepted method for definitive diagnosis of NASH 2, as it is the only way to distinguish NASH from simple steatosis and accurately assess the degree of inflammation, ballooning, and fibrosis. While various non-invasive tests exist to characterize NAFLD, they cannot definitively diagnose NASH.
Important Clinical Pitfall
The term "NASH" should not be used interchangeably with "NAFLD." NAFLD encompasses the entire spectrum from simple steatosis to NASH to cirrhosis 1, while NASH specifically refers to the inflammatory subtype with hepatocyte injury. This distinction is critical because only NASH carries significant risk of progression to cirrhosis and liver-related mortality, making accurate identification essential for risk stratification and management decisions.