lenvatinib and Hepatic-Encephalopathy

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.. 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.. 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.. 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.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Neoplasms; Phenylurea Compounds; Quinolines; Retrospective Studies; Risk Factors; Sorafenib

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

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Bilirubin; Carcinoma, Hepatocellular; Disease Susceptibility; Female; Hepatic Encephalopathy; Humans; Hyperammonemia; Liver Function Tests; Liver Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Phenylurea Compounds; Portal Vein; Protein Kinase Inhibitors; Quinolines; Risk Factors

We report a 74-year-old male patient with compensated cirrhosis after hepatic C virus eradication. After the patient underwent hepatectomy for hepatocellular carcinoma, multiple lung and lymph node metastases were detected by computed tomography. Computed tomography also revealed a portosystemic shunt from the superior mesenteric vein to the right testicular vein. He was administered lenvatinib (12 mg). Five days after the initiation of lenvatinib, he developed grade 3 hepatic encephalopathy, and his ammonia level increased. Lenvatinib was stopped, with improvement of the encephalopathy and decrease in ammonia level. When lenvatinib was restarted, grade 2 encephalopathy recurred which then improved upon stopping the drug. We thought that the encephalopathy was due to the portosystemic shunt, and occlusion of the shunt was performed. The day after shunt occlusion, lenvatinib (8 mg) was restarted, and the lenvatinib dose was increased to 12 mg at 2 days after shunt occlusion. Subsequently, the ammonia level remained stable and the patient remained alert and conscious. Lenvatinib was continued until the time of this report (40 days after shunt occlusion), and after 1 month of lenvatinib therapy, the computed tomography verified absence of the portosystemic shunt and stable disease of hepatocellular carcinoma.

Topics: Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Embolization, Therapeutic; Hepatic Encephalopathy; Humans; Liver Neoplasms; Male; Mesenteric Veins; Phenylurea Compounds; Quinolines; Testis; Tomography, X-Ray Computed; Vascular Fistula