The Impact of Rifaximin on Hepatic Encephalopathy during Lenvatinib Therapy in Patients with Hepatocellular Carcinoma and Splenorenal Shunt.

Objective Hepatic encephalopathy (HE) is a serious adverse event associated with lenvatinib (LEN) that requires discontinuation of the medication. We investigated the risk factors for HE in patients with hepatocellular carcinoma (HCC) who received LEN. We also explored the usefulness of rifaximin in preventing HE and LEN. Methods We enrolled 216 patients with HCC who had undergone LEN. The incidence of HE was evaluated [observational period 171 (1-2,079) days]. LEN dosage was assessed using the relative dose intensity (RDI). A decision-tree algorithm was constructed to reveal the profiles associated with HE. Results The incidence rate of HE was 8.8%. There were no significant differences in the age, sex, body mass index, or tumor stage between the HE and non-HE groups. A splenorenal shunt (≥8 mm in diameter) was identified as an independent risk factor for HE (hazard ratio 7.653, 95% confidence interval 2.489-23.535, p<0.001). A decision-tree analysis revealed that, in patients with splenorenal shunt and ALBI grade 2, HE occurred in 66.6% of patients with no refaxmin. In contrast, 16.6% developed HE in patients treated with rifaximin. Furthermore, the prevalence of RDI >70% was 20.0% and 66.7% in patients who did not receive rifaximin and rifaximin, respectively. Conclusion Splenorenal shunt placement is an independent risk factor for HE in patients with HCC receiving LEN. Furthermore, rifaximin prevented HE and contributed to a sufficient dose of LEN in patients with HCC, splenorenal shunts, and ALBI grade 2. Thus, rifaximin may be beneficial for the management of patients with HCC receiving LEN, especially those with HCC with splenorenal shunt and hepatic dysfunction.