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Most disease processes cause ALT to rise higher than AST; AST levels double or triple that of ALT are consistent with alcoholic liver disease. [citation needed] When the AST is higher than ALT, a muscle source of these enzymes should be considered. For example, muscle inflammation due to dermatomyositis may cause AST>ALT.
The proportion of AST to ALT in hepatocytes is about 2.5:1, but because AST is removed from serum by the liver sinusoidal cells twice as quickly (serum half-life t 1/2 = 18 hr) compared to ALT (t 1/2 = 36 hr), so the resulting serum levels of AST and ALT are about equal in healthy individuals, resulting in a normal AST/ALT ratio around 1.
When ALT rises to more than 500 IU/L, causes are usually from the liver. It can be due to hepatitis, ischemic liver injury, and toxins that causes liver damage. The ALT levels in hepatitis C rises more than in hepatitis A and B. Persistent ALT elevation more than 6 months is known as chronic hepatitis.
AST and ALT blood levels are both elevated, but at less than 300 IU/liter, with an AST:ALT ratio > 2.0, a value rarely seen in other liver diseases. [52] In the United States, 40% of cirrhosis-related deaths are due to alcohol. [33] In non-alcoholic fatty liver disease (NAFLD), fat builds up in the liver and eventually causes scar tissue. [53]
In people with alcoholic hepatitis, the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is greater than 2:1. AST and ALT levels are almost always less than 500. The elevated AST to ALT ratio is due to deficiency of pyridoxal phosphate, which is required in the ALT
Septerna’s decision follows the observation of two unanticipated severe (Grade 3) events of elevated unconjugated bilirubin in the MAD portion of the Phase 1 trial, both of which were without elevations in ALT, AST, and GGT liver enzyme levels. Dosing was discontinued for both study participants, and the bilirubin elevations were reversible.
[71] [72] Generally, AST and ALT are elevated in most cases of hepatitis regardless of whether the person shows any symptoms. [33] The degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis. [33]
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