There are several types of drug-induced liver injury (DILI) that may be observed in patients treated for cancer even years after publicity, and diagnosing it may be difficult to detect, according to a speaker on the 2021 virtual annual meeting of the Hematology/Oncology Pharmacy Association. That’s why “DILIgence” is required on the part of clinicians.
“While DILI by itself is difficult to diagnose and manage, cancer patients and their therapies have characteristics that make it a uniquely difficult activity,” said E. Dan Nichols, PharmD, BCOP, a clinical pharmacy specialist with The University of Texas MD Anderson Cancer Center, in Houston.
The impact of multiple medications is something to watch for, commented Mario Strazzabosco, MD, Ph.D., the director and scientific program chief of the Smilow Liver Cancer Program, a part of the Yale Cancer Center in New Haven, Conn. “Drugs that might not be hepatotoxic per se could grow to be so due to their interplay with others concomitantly [consumed],” he said. Sure drugs comparable to immune checkpoint inhibitors can also set off autoimmune hepatitis in predisposed patients, he added.
Though it may be difficult to find out the propensity of a medication to trigger DILI, some patient- and drug-specific risk factors have been identified, Dr. Nichols stated, comparable to older age, malnutrition, comorbidities, genetic variability, polypharmacy, and drugs with some mechanisms of hepatotoxicity. Many of those traits are prevalent among cancer patients.
Managing DILI is relatively simple, however, could be strenuous, Dr. Nichols added. The case is a prognosis of exclusion, he said, “so earlier than pointing to a medication as the reason for the affected person’s liver impairment, it’s essential to rule out different potential causes, such as biliary abnormalities, viral hepatitis, alcohol use, and hemodynamic instability.”
Cancer patients require an even wider differential diagnosis as a result of disease involvement in the liver, comparable to metastasis, additionally may need to be ruled out. With no dependable marker but recognized to establish DILI as a definitive reason for the injury, most regulatory bodies use the Roussel Uclaf Causality Assessment Method (RUCAM), an objective, point-based system that combines clinical, biochemical, serologic, and radiological options of liver injury to assign an overall score that reflects the probability that hepatic injury is due to a specific medication. This assessment method accounts for variables comparable to the onset of symptoms, risk factors, age, and medication or nonmedication causes. If several potential hepatotoxic brokers are used concurrently, a separate score should be calculated for each, Dr. Nichols said.
As soon as a medication has been implicated as the reason for liver injury, the treatment is easy: Cease the offending agent. “Most circumstances of DILI will resolve spontaneously as soon as publicity is halted, and persevering with therapy will increase the risk for more serious or persistent harm,” he said. Supportive care together with fluids, antiemetics, or steroids could be applied. Resuming medications typically is strongly discouraged, however, it could be affordable for cancer therapies if no alternative brokers exist and the patient has a curable disease.
When seeking hepatotoxicity information of particular drugs, clinicians often first turn to package deal inserts, or databases comparable to Lexicomp, Dr. Nichols said. But some limitations warrant a deeper dive. DILI is described in a wide variety of ways throughout medication package inserts and relatively contains classified information. Information on liver toxicity in the labels of oncology agents is primarily based on hepatotoxicity recognized throughout scientific improvement rather than post-marketing information, which can underestimate the real-world risk for DILI, he cautioned. Data on hepatotoxicity additionally could fluctuate in keeping with patient populations and how therapies were used.
A valuable resource to check is the LiverTox database (livertox.nih.gov) produced by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Library of Drugs, Dr. Nichols said. It contains descriptions of the hepatotoxicity of greater than 1,000 drugs and allows customers to submit case reports. Clinicians can also report drug-related adverse results, together with hepatotoxicity, to the FDA’s MedWatch database at www.fda.gov/medwatch.