Question: Which of the following biomarkers makes you most worried that your patient with metabolic syndrome and NASH has advanced to cirrhosis?
A. ALT > 400
B. alkaline phosphatase > 250
C. INR 1.2
D. AST:ALT > 1
Answer: We are only beginning to understand the natural history of non-alcoholic steatohepatitis. Also, we are a long way from being able to predict the natural history of disease in its earliest stages.
Routine labs are sometimes helpful in predicting the stage of disease. Usually in NASH, the ALT is greater than AST (compared to alcoholic liver disease, where the AST:ALT ratio is around 2:1). However, when the liver becomes cirrhotic, this ratio can reverse, so AST:ALT will be > 1. This is the most correct answer.
Having a high ALT, or a high alkaline phosphatase does not help stage the disease. In fact, the meaning of an elevated alkaline phosphatase in NASH is unknown; is it related to a primary biliary process, or perhaps a problem with the arterial supply of the biliary tree?
A slightly elevated INR, while sometimes indicative of synthetic dysfunction of the liver, is too non-specific to draw any firm conclusions. A value of 1.2 could easily be 1.0 or 1.1 if redrawn the following week, so I wouldn’t put too much stock in that.
We still don’t know if the non-invasive serologic markers of fibrosis are valid in NASH; they may underestimate the degree of fibrosis. Ultimately, a liver biopsy is needed these days for proper staging. For more about the natural history of NASH in its advanced stages, please refer to this Hepatology article, October 2011 issue. In it, a cohort of NASH patients with advanced fibrosis is compared to a cohort of HCV patients with advanced fibrosis.