Side Effect: Elevated Liver Function Tests (LFTS, transaminases)

Liver function tests (LFTs) are a set of laboratory tests that measure the levels of certain enzymes and proteins in the blood that are produced by the liver. These tests typically include:

• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Gamma-glutamyl transferase (GGT)
• Alkaline phosphatase (ALP)

• ALT and AST are enzymes that are primarily found in liver cells.
• When liver cells are damaged or destroyed, these enzymes leak into the bloodstream, leading to elevated levels in the blood.
• GGT is an enzyme that is found primarily in the liver but is also present in other tissues such as the kidney and pancreas.
  • When GGT levels are elevated, this indicated that there may be damage to the liver.
• ALP is an enzyme that is found in the liver, bones and other tissues. Elevated ALP can be indicative of liver or bone disease.

• Elevated liver enzymes can be seen in a variety of conditions, including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease, autoimmune liver disease, liver cancer (also called hepatocellular carcinoma or HCC), or other cancers that have metastasized to the liver.
• Patients with certain medical conditions such as obesity, diabetes, and metabolic syndrome are at an increased risk of developing elevated liver enzymes as these conditions may play a role in liver damage if not controlled in time.

In patients receiving cancer treatment, there are many drugs that can damage the liver which can lead to changes in liver function tests. Examples of chemotherapy agents that can cause liver damage include:

• Doxorubicin (Adriamycin®)
• Busulfan (Busulfex®)
• Melphalan (Evomela®, Alkeran®)
• Platinums: oxaliplatin (Eloxatin®), cisplatin (Platinol®), carboplatin (Paraplatin®)
• Cyclophosphamide (Cytoxan®)
• Methotrexate (Trexall®)
• Cytarabine (Ara-C)
• Gemcitabine (Gemzar®)
• Taxanes: paclitaxel (Taxol®), docetaxel (Taxotere®)
• Vinca alkaloids: vincristine (Oncovin®), vinblastine (Velban®)
• Topoisomerase inhibitors: irinotecan (Camptosar®), etoposide (VP-16)
• HER-2 inhibitors: trastuzumab (Herceptin®, Kanjinti®, Trazimera®) , lapatinib (Tykerb®)
• Small molecular tyrosine kinase inhibitors: imatinib (Gleevec®), gefitinib (Iressa®), crizotinib (Xalkori®), sorafenib (Nexavar®), bosutinib (Bosulif®), nilotinib (Tasigna®), pazopanib (Votrient®), regorafenib (Stivarga®), sunitinib (Sutent®)
• Immunotherapy such as pembrolizumb (Keytruda®) or nivolumab (Opdivo®)

Preventing liver function changes in patients with cancer can be challenging. Ideally, patients should try to maintain a healthy lifestyle by:

• eating a balanced diet
• exercising regularly
• avoiding excessive alcohol consumption
• avoiding exposure to hepatitis viruses

Patients should be carefully screened before treatment to identify any risk factors that could increase the risk of developing elevated liver function tests. During treatment, patients should be monitoring closely for changes in liver function tests. If transaminases (LFTs) rise too high as a result of taking chemotherapy, your doctor may recommend holding the dose, decreasing the dose, or changing to an alternative treatment.

Treatment of elevated liver function tests in cancer patients depends on the underlying cause of liver dysfunction.

• In patients receiving immunotherapy who develop elevated liver function tests due to liver inflammation, treatment may consist of:
  • corticosteroids such as prednisone (Deltasone®) or methylprednisolone (Medrol®, Solu-Medrol®)
  • other immunosuppressive agents such as mycophenolate (Cellcept®).
• In some cases, therapy that may be causing the changes in liver function may need to be temporarily stopped or the dose may need to be reduced.
• In patients with cancer of the liver (hepatocellular carcinoma), or in the liver, treatment of the cancer may be required.