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

Oncology. 2020;98(10):727-733. doi: 10.1159/000507815. Epub 2020 Jul 24.

Abstract

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.

Keywords: Hepatic reserve; Hepatocellular carcinoma; Lenvatinib; Sorafenib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / physiopathology*
  • Cohort Studies
  • Female
  • Humans
  • Liver / physiopathology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / physiopathology*
  • Male
  • Middle Aged
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinolines / therapeutic use
  • Retrospective Studies
  • Sorafenib / therapeutic use
  • Young Adult

Substances

  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • Sorafenib
  • lenvatinib