Trends in Hepatic Functional Reserve of Patients with Hepatocellular Carcinoma Treated with Tyrosine Kinase Inhibitors

Objective:Functional hepatic reserve is important when considering sequential tyrosine kinase inhibitor (TKI) therapy for patients with advanced hepatocellular carcinoma (HCC). We assessed albumin-bilirubin (ALBI) score and Child-Pugh class as indices of liver function during sorafenib and lenvatinib treatment.Methods:A total of 212 patients with advanced HCC and Child-Pugh class A status who initiated TKI treatment at our hospital were enrolled in this retrospective cohort study. A total of 74 of the 212 patients underwent blood testing before starting sorafenib treatment and every 2 months after treatment initiation.Results:In 74 patients, the median ALBI score before TKI treatment was -2.53, and after 2, 4, and 6 months it was -2.45, -2.44, and -2.36, respectively. ALBI scores tended to increase during TKI therapy. Among patients who experienced a time to progression <= 3.8 months, ALBI scores had increased 2 months after treatment initiation, and at 4 and 6 months, significant differences were observed (p< 0.01). In all 212 patients, during first-line TKI treatment, the Child-Pugh class deteriorated to B or C in 72.2% of the patients, and the median time to deterioration was 3.9 months. The factors in hepatic reserve deterioration were serum albumin <= 3.8 g/dL and the presence of macroscopic vascular invasion. The hepatic reserve of 68.0% of the patients with deterioration of liver function recovered to Child-Pugh class A following dose reduction, drug withdrawal, or treatment intended for recovery of liver function.Conclusion:ALBI scores deteriorate in patients treated with TKIs, suggesting that tumor progression induces these changes.