From the Guidelines
Yes, liver function tests should be monitored in patients taking Alyftrek (Ivacaftor) for cystic fibrosis, with annual labs including total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyl transferase (GGT), and platelet count, as recommended by the Cystic Fibrosis Foundation 1. The Cystic Fibrosis Foundation recommends annual liver function tests for all patients with cystic fibrosis, starting at diagnosis, to identify hepatobiliary involvement 1. This is because liver test abnormalities may precede imaging abnormalities and correlate with fibrosis, and early identification of cystic fibrosis-related hepatobiliary disease can affect care through staging, regular monitoring, and treatment 1.
- The recommended tests include:
- Total bilirubin
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT)
- Alkaline phosphatase
- Gamma-glutamyl transferase (GGT)
- Platelet count
- These tests should be performed at a time of clinical stability, and further evaluation is recommended if any abnormalities are persistent (> 3-6 months) 1. The Cystic Fibrosis Foundation also recommends that patients with cystic fibrosis and hepatobiliary involvement undergo baseline liver elastography, when available, for the identification of advanced liver disease, and receive a standardized evaluation for other causes of liver disease 1.
- Additionally, patients with cystic fibrosis and advanced liver disease should undergo liver-specific physical examination and measurement of AST, ALT, GGT, alkaline phosphatase, conjugated (or direct) bilirubin, albumin, platelets, and international normalized ratio (INR) at least every 6 months to detect progression of liver disease 1. Monitoring liver function is crucial in patients taking Alyftrek, as cystic fibrosis patients often have underlying liver involvement due to their disease, making them potentially more susceptible to drug-induced liver injury 1.
From the Research
Liver Function Tests in Patients Taking Alyftrek (Ivacaftor) for Cystic Fibrosis
- Monitoring of liver tests is recommended due to observed rises in transaminases in trials and cases of hepatotoxicity 2
- A study found that E/T/I therapy leads to a mild, likely clinically insignificant increase in ALT, AST, and bilirubin after 3 months, which is sustained but does not appear to increase further in the vast majority of patients 2
- Clinically significant rises in ALT and AST occurred in 8 (3.1%) and 6 (2.4%) cases, respectively, with derangements in 2 individuals attributed to therapy 2
Importance of Liver Function Tests in Cystic Fibrosis Patients
- Liver disease in adults with cystic fibrosis is commonly complicated by portal hypertension, but morbidity and mortality associated with this are low 3
- Ursodeoxycholic acid (UDCA) is associated with improvement in hepatobiliary symptoms and liver function tests in cystic fibrosis patients with liver disease 3, 4
- High-molecular-mass ("biliary") isoenzyme of alkaline phosphatase is a highly sensitive index to cholestasis and can be used as a diagnostic marker for liver dysfunction in cystic fibrosis patients 5
Screening for Cystic Fibrosis-related Liver Disease
- Extended screening for cystic fibrosis-related liver disease, including elastography, can help identify patients with liver fibrosis, portal hypertension, and liver decompensation 6
- A combination of biochemical markers, ultrasound, and elastography can be used to diagnose and monitor cystic fibrosis-related liver disease in children and adolescents 6