Factors Raising Serum Ammonia Level During Lenvatinib Treatment of Patients With Hepatocellular Carcinoma

Anticancer Res. 2020 Sep;40(9):5271-5276. doi: 10.21873/anticanres.14531.

Abstract

Background/aim: Hepatic encephalopathy is an adverse event resulting from lenvatinib use in patients with hepatocellular carcinoma (HCC). We analyzed the influence of lenvatinib on portal venous flow velocity (PVV) and serum ammonia concentration.

Patients and methods: Eleven patients with unresectable HCC were enrolled, including three with modified albumin-bilirubin (mALBI) grade 1, three with grade 2a, and five with grade 2b. PVV was measured by Doppler ultrasound sonography before and on day 2 of administration.

Results: Out of 11 patients, one developed hepatic encephalopathy. PVV was reduced in 10 patients, and the change from baseline was significantly correlated with lenvatinib dosage. The increase in serum ammonia concentration was affected by lenvatinib dose and baseline hepatic function as a threshold between mALBI grade 2a and 2b statistically. There was no correlation between changes in PVV and serum ammonia concentration.

Conclusion: Lenvatinib might directly disturb hepatocyte metabolism to result in increased serum ammonia concentration.

Keywords: Hepatocellular carcinoma; hepatic encephalopathy; lenvatinib; portal vein flow velocity.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Bilirubin / blood
  • Carcinoma, Hepatocellular / complications*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy*
  • Disease Susceptibility
  • Female
  • Hepatic Encephalopathy / diagnosis
  • Hepatic Encephalopathy / etiology
  • Humans
  • Hyperammonemia / diagnosis
  • Hyperammonemia / etiology*
  • Liver Function Tests
  • Liver Neoplasms / complications*
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Portal Vein / physiopathology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Quinolines / administration & dosage
  • Quinolines / adverse effects*
  • Quinolines / therapeutic use
  • Risk Factors

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • lenvatinib
  • Bilirubin