What is the significance if Alanine Transaminase (ALT) is double Aspartate Transaminase (AST)?

From the Guidelines

When ALT is double the level of AST, it typically suggests liver damage specifically related to conditions like viral hepatitis, medication-induced liver injury, or non-alcoholic fatty liver disease. This pattern is significant because it differs from alcoholic liver disease, where AST is usually higher than ALT, with a ratio greater than 2, as noted in 1. The elevation of ALT and AST occurs because these enzymes leak into the bloodstream when liver cells are damaged. The ratio of AST to ALT, known as the De Ritis ratio, can help differentiate between various liver conditions, with a ratio less than 1 often indicating acute hepatocellular injury, as seen in 1. Some key points to consider in this scenario include:

• The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease and <1 in metabolic disease-related fatty liver, as stated in 1.
• Non-alcoholic fatty liver disease (NAFLD) is a common cause of fatty liver disease, with a prevalence of 20% to 30% in the general population, increasing to 70% with obesity and 90% with diabetes mellitus, as reported in 1.
• The elevation of ALT is directly linked to hepatocyte injury, and common causes of rising ALT include acute or chronic viral hepatitis, acute Budd-Chiari syndrome, ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins, and Wilson disease, as mentioned in 1. If you have this pattern on your liver function tests, further evaluation is recommended, including a complete medical history, physical examination, and possibly additional tests like viral hepatitis panels, ultrasound, or other imaging studies to determine the specific cause of liver damage, as suggested by the information in 1 and 1.

From the Research

Significance of ALT being double AST

• The significance of Alanine Transaminase (ALT) being double Aspartate Transaminase (AST) can be indicative of liver damage, as ALT is a more specific marker for liver damage compared to AST 2.
• A study published in 2019 found that the differential diagnosis of an increase in ALT level and/or AST level often includes ischemic hepatitis, acute viral hepatitis, and drug-induced liver injury (DILI) 3.
• In cases where ALT is double AST, it may be necessary to investigate non-hepatic causes of raised ALT and AST, such as polymyositis, acute muscle injury, acute myocardial infarction, and hypothyroidism 4.
• Mildly elevated liver transaminase levels, including ALT and AST, can be caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease, among other conditions 5.
• Vitamin E has been shown to be effective in reducing NAFLD, with improvements in ALT and AST levels, as well as NAFLD activity score (NAS) and fibrosis 6.

Possible Causes

• Liver damage or disease, such as hepatitis or cirrhosis 2, 3
• Nonalcoholic fatty liver disease (NAFLD) 5, 6
• Alcoholic liver disease 5
• Drug-induced liver injury (DILI) 3
• Ischemic hepatitis 3
• Acute viral hepatitis 3
• Non-hepatic causes, such as polymyositis, acute muscle injury, acute myocardial infarction, and hypothyroidism 4

Evaluation and Management

• Initial evaluation should include an assessment for metabolic syndrome and insulin resistance, as well as testing for common causes of elevated transaminase levels 5.
• If testing for common causes is consistent with NAFLD and is otherwise unremarkable, a trial of lifestyle modification may be appropriate 5.
• Vitamin E may be considered as a treatment option for NAFLD, with improvements in ALT and AST levels, as well as NAS and fibrosis 6.