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

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 mu mol/L [OR: 4.693 (95% CI: 1.782-12.358)], total bile acid >= 29.5 mu mol/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, hypercholester-olemia, and estimated longer duration of treatment, the application of lenvatinib has to be cautious, which needs to be confirmed in future clinical trials.