Non-Alcoholic Steatohepatitis (NASH) is a severe form of liver disease linked to metabolic dysfunction. It is the progressive stage of Nonalcoholic Fatty Liver Disease (NAFLD), where fat accumulation escalates to include inflammation and cellular injury, risking cirrhosis and liver failure. Accurate assessment of this progressive damage is paramount for patient management. To standardize the evaluation of disease activity, clinicians and researchers use the NAFLD Activity Score, or NAS, which provides a numerical assessment of liver injury.
Defining the NASH Score
The scoring system used to assess Non-Alcoholic Steatohepatitis activity is formally known as the NAFLD Activity Score (NAS). This histological tool requires the microscopic examination of a liver tissue sample obtained through a biopsy. The NAS was developed by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) to provide a standardized, semi-quantitative measure. Its function is to quantify the severity of active liver injury and inflammation. This activity score is distinct from the assessment of fibrosis, which measures scarring and is staged separately.
The Three Key Components of the Score
The NAS is derived from the pathologist’s grading of three specific features of liver injury: steatosis, lobular inflammation, and hepatocyte ballooning. These components are graded individually before being summed. Each component’s grade reflects the extent of observable damage under the microscope.
Steatosis (Fat Accumulation)
Steatosis refers to the accumulation of fat, specifically triglycerides, within the liver cells (hepatocytes). This component is graded based on the percentage of liver tissue area involved by the fatty change, primarily macrovesicular fat. The scoring ranges from 0 to 3:
- Score 0 indicates less than 5% of cells are affected.
- Score 1 means 5-33% of cells are affected.
- Score 2 means 33-66% of cells are affected.
- Score 3 is assigned when more than 66% of the hepatocytes contain fat droplets.
Lobular Inflammation (Immune Cell Presence)
Lobular inflammation measures the presence and density of inflammatory cells, such as lymphocytes and macrophages, scattered throughout the liver lobules. These cells indicate an ongoing immune response and active injury. The scoring for this component ranges from 0 to 3, based on the number of inflammatory cell clusters (foci) visible in a standard microscopic field:
- Score 0 means no foci are present.
- Score 1 indicates less than two foci per high-power field.
- Score 2 denotes two to four foci.
- Score 3 is given for more than four foci per field.
Hepatocyte Ballooning (Cell Swelling/Injury)
Hepatocyte ballooning describes a specific type of liver cell injury where hepatocytes swell and become rounded due to cytoskeletal damage. This cellular swelling represents the most advanced stage of active cell damage. This feature is scored from 0 to 2, reflecting the severity and prevalence of the damaged cells. A score of 0 indicates no ballooned cells, 1 is given for a few scattered ballooned cells, and a score of 2 signifies many or prominent ballooned cells.
Calculating and Interpreting the Score
The total NAFLD Activity Score is calculated by summing the individual scores for the three components: Steatosis (0-3), Lobular Inflammation (0-3), and Hepatocyte Ballooning (0-2). This summation results in a total score that can range from 0 to 8. The final number provides a consolidated metric for the overall necroinflammatory activity within the liver tissue.
The resulting NAS is used to interpret the severity of the disease activity. In a clinical context, specific thresholds categorize the likelihood of Non-Alcoholic Steatohepatitis. A low score (0 to 2) suggests the case is not diagnostic of NASH, often indicating simple steatosis with minimal inflammation. An intermediate score (3 or 4) is considered borderline or possible NASH. A high score (5 to 8) strongly correlates with active, definite NASH. The ultimate diagnosis of NASH relies on the pathologist’s overall assessment of the tissue pattern.
Clinical Application and Monitoring
The NAS extends beyond the initial diagnostic assessment of a liver biopsy. It acts as a standardized, objective measure for tracking the progression or regression of liver disease activity over time. By comparing NAS values from biopsies taken at different points, clinicians can quantitatively determine if the disease activity is worsening, stable, or improving.
This scoring system has become a primary tool in drug development and clinical trials for new NASH therapeutics. Regulatory bodies often accept a significant reduction in the NAS, typically defined as an improvement of two or more points, as an endpoint for determining a drug’s efficacy. Using a standardized score allows researchers globally to compare the effects of different treatments on the disease’s active components.