Risk Factors for Hepatic Encephalopathy in Hepatocellular Carcinoma After Sorafenib or Lenvatinib Treatment: A Real-World Study

Drug Des Devel Ther. 2022 Dec 28:16:4429-4437. doi: 10.2147/DDDT.S386829. eCollection 2022.

Abstract

Purpose: This study aimed to investigate the incidence rate and risk factors for hepatic encephalopathy (HE) among unresectable hepatocellular carcinoma (uHCC) patients with liver cirrhosis who received sorafenib or lenvatinib treatment.

Patients and methods: uHCC patients with cirrhosis who received first-line sorafenib or lenvatinib treatment between September 2014 and February 2021 were continually reviewed in our single-center retrospective study. The Hepatic Encephalopathy Scoring Algorithm was used to evaluate the occurrence and grade of HE during treatment, and logistic regression models were used to further explore the risk factors for HE.

Results: A total of 454 eligible patients were enrolled in our study, with 214 and 240 patients in the sorafenib and lenvatinib groups, respectively. At time of data cut-off (2021-12), the incidence of HE in sorafenib group (4.2%, 95% CI:2-7%) was significantly lower than that in lenvatinib group (11.3%,95% CI:7-15%) (p = 0.006), with alcoholic cirrhosis [OR: 5.857 (95% CI: 1.519-22.591)], Child-Pugh >7 [OR: 3.023 (95% CI: 1.135-8.053)], blood ammonia ≥38.65 μmol/L [OR: 4.693 (95% CI: 1.782-12.358)], total bile acid ≥29.5 μmol/L [OR: 11.047 (95% CI: 4.414-27.650)] and duration of treatment ≥5.6 months [OR: 4.350 (95% CI: 1.701-11.126)] to be risk factors for the occurrence of HE during first-line systemic therapy.

Conclusion: In our study, for off-label uHCC patients (Child-Pugh >7) with alcoholic cirrhosis, hyperammonemia, hypercholesterolemia, and estimated longer duration of treatment, the application of lenvatinib has to be cautious, which needs to be confirmed in future clinical trials.

Keywords: hepatic encephalopathy; hepatocellular carcinoma; lenvatinib; liver cirrhosis; sorafenib.

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Carcinoma, Hepatocellular* / chemically induced
  • Carcinoma, Hepatocellular* / drug therapy
  • Hepatic Encephalopathy* / chemically induced
  • Hepatic Encephalopathy* / drug therapy
  • Hepatic Encephalopathy* / epidemiology
  • Humans
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis, Alcoholic / complications
  • Liver Cirrhosis, Alcoholic / drug therapy
  • Liver Neoplasms* / drug therapy
  • Phenylurea Compounds / adverse effects
  • Quinolines* / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Sorafenib / adverse effects

Substances

  • Sorafenib
  • lenvatinib
  • Antineoplastic Agents
  • Phenylurea Compounds
  • Quinolines

Grants and funding

Project title: Study on the techniques for comprehensive early diagnosis of liver cancer with clinical application. Program name: Special program of sustainable development. Grant support: Issued by the Science, Technology and Innovation Commission of Shenzhen Municipality. Grant No. KCXFZ202002011006448.