Mr. Li, 35, is a terminal lung cancer patient, and although it is unfortunate to have advanced lung cancer, he is fortunate than other patients, and his genetic tests have revealed a mutation in the ALK fusion gene, which belongs to the "diamond mutation". So began oral aletinib, ate less than two months, re-examined blood routine and biochemistry, found that the liver function in the transaminases has been as high as more than 300, bilirubin slightly elevated, at this time he was shocked to feel tired recently, it turned out that the liver function is not good. The transaminases are so high that the drug must be temporarily stopped, and the liver-protecting enzyme-lowering enzyme treatment must be started.
Targeted drugs have always been known for their "low toxicity and high efficiency", but the toxicity of targeted drugs is not small, such as rashes and diarrhea, and the incidence is relatively high. Secondly, damage to liver function is also present in many targeted drugs. As we all know, there are currently three generations of 5 targeted drugs for the ALK gene, all of which have different degrees of liver toxicity.
It can be said that drug-related liver injury (DILI) is a relatively common adverse reaction of ALK targeted drugs, and the main judgment is based on the increase of laboratory indicators such as serum alanine transaminases (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and total bilirubin (TBiL).
Targeted agent-related liver function impairment may be asymptomatic, or there may be some nonspecific symptoms such as fatigue, loss of appetite, anorexia, liver swelling pain, and gastrointestinal symptoms such as epigastric discomfort. Patients with elevated bilirubin may have yellowing of the sclera, lighter stool color, and itchy skin. A small number of patients may have allergic manifestations such as fever, rash, eosinophilia, and even arthralgia, and may also be accompanied by other extrahepatic organ damage.
The overall incidence of elevated liver enzymes of grades 3 to 4 is below 30%, and the actual progression to severe jaundice is relatively rare, and in most cases, elevated liver enzymes is not an indication of immediate discontinuation. However, when the total bilirubin TBIL is elevated, it needs to be taken seriously, and if the drug is continued, it may induce the risk of liver failure.
Dose adjustment of adverse reactions to liver injury of different ALK targeted drugs can also be recommended by reference to drug instructions, such as ceritinib recommended: when ALT or AST>5× ULLN, total bilirubin < 2 times normal value, the drug should be stopped until the ALT/AST returns to baseline or < 3 times normal value, and the dose of 150 mg slowly returns to normal. The drug should be discontinued when ALT or AST>3× ULLN, total bilirubin >2× ULN (no cholestasis or hemolysis) should be discontinued.
Since the off-target effect of targeted agents has the potential to lead to activation of hepatitis B virus, HBV DNA levels should be tested before initiating TKIs in HBsAg-positive anti-HBS Ag-negative/anti-HBBC-positive patients receiving targeted therapy. For patients with high levels of HBVDNA, prophylactic antiviral therapy may be considered. In patients with known HBV infection, regular liver function tests (including AST, ALT) are recommended every 4 weeks and monitoring of HBV viral load levels before and after treatment with TKIs, or when liver function abnormalities occur, and antiviral therapy should be considered once HBV DNA levels are elevated.