Elevated levels of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are common findings in routine blood tests. These enzymes are released into the bloodstream when liver cells are injured. While the presence of cancer can certainly lead to high AST and ALT, it is important to understand that these elevations are not specific to malignancy. Far more frequently, non-cancerous conditions are the underlying cause of abnormal liver enzyme readings.
Understanding Liver Enzymes AST and ALT
Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) are enzymes that play a role in the liver’s metabolism. ALT is concentrated predominantly within the liver, making it a specific indicator of liver cell injury. AST is found in the liver, but also in other organs, including the heart, skeletal muscles, kidneys, and brain; damage to any of these tissues can cause AST to leak into the blood. Typically, AST is expected to be between 5 to 40 units per liter (U/L) and ALT from 7 to 56 U/L. Medical professionals often look at the ratio of AST to ALT, known as the De Ritis ratio, as this relationship can offer diagnostic clues about the type of liver condition present.
How Cancer Directly Causes Elevated AST and ALT
Cancer can cause liver enzyme elevation through several distinct mechanisms. Primary liver cancers, such as hepatocellular carcinoma (HCC), originate within the liver and destroy surrounding healthy cells as the tumor grows. This cellular destruction causes the internal enzymes, including AST and ALT, to spill out into the circulation.
A more common scenario involves metastatic cancer, where a malignancy that began elsewhere in the body spreads to the liver. Cancers originating in the colon, breast, or pancreas frequently metastasize, and the growing secondary tumors physically destroy a large number of liver cells.
Another mechanism involves tumors that cause an obstruction, such as cholangiocarcinoma or pancreatic cancer near the bile ducts. This blockage can cause bile to back up into the liver, leading to damage of liver cells and the release of enzymes, although this is more commonly associated with elevations in other liver markers like alkaline phosphatase (ALP). Non-liver cancers can cause enzyme elevation through paraneoplastic syndromes, where the cancer produces substances that affect distant organs. The finding of an AST/ALT ratio greater than 1.0 in a patient without a history of alcohol abuse may raise suspicion for advanced liver fibrosis or metastatic liver disease.
Non-Cancer Factors That Elevate Liver Enzymes
The most common cause in the United States is Non-Alcoholic Fatty Liver Disease (NAFLD), which is strongly linked to obesity, diabetes, and metabolic syndrome. Fat accumulation in the liver cells causes inflammation and injury, leading to a chronic, mild to moderate elevation of liver enzymes.
Excessive alcohol consumption is another major contributor, causing alcoholic hepatitis or steatohepatitis, where the AST level often exceeds the ALT level by a ratio of two-to-one or more. Viral infections, particularly Hepatitis A, B, and C, induce inflammation that destroys liver cells and raises enzyme levels.
A variety of medications, including common over-the-counter pain relievers like acetaminophen, cholesterol-lowering statins, and certain antibiotics, can also induce liver injury. This drug-induced liver injury can range from mild, temporary elevation to severe liver failure.
Conditions outside the liver, such as muscle injury from intense exercise or muscle disorders like polymyositis, can also raise AST levels due to its presence in muscle tissue. When elevated enzymes are detected, a detailed medical history is critical, focusing on diet, alcohol use, medication, and recent viral exposure. Further diagnostic testing, such as imaging studies like ultrasound, or blood tests for viral hepatitis, are typically used to differentiate these common non-cancerous causes from the possibility of malignancy.
Monitoring Enzyme Levels During Cancer Treatment
Liver enzyme monitoring becomes a routine part of treatment to assess for drug-induced liver toxicity. Many cancer therapies, including traditional chemotherapy agents, targeted therapies, and modern immunotherapies, can cause hepatotoxicity. The liver is responsible for metabolizing many of these drugs, and the process can damage liver cells, causing AST and ALT levels to rise.
Doctors use a grading system to categorize the severity of enzyme elevation, which helps guide treatment adjustments. If transaminase levels become too high, the cancer treatment dose may need to be reduced or temporarily withheld to allow the liver time to recover.
Immune checkpoint inhibitors, a type of immunotherapy, can trigger immune-related adverse events, where the immune system mistakenly attacks the liver. This results in significant enzyme elevation that requires specific medical intervention. Persistently high or rising enzyme levels during treatment can also have prognostic value, sometimes signaling that the cancer is progressing or that the treatment is failing to control the disease in the liver.