Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib.


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Oct 2022
Historique:
received: 09 07 2022
revised: 28 07 2022
accepted: 06 08 2022
entrez: 3 10 2022
pubmed: 4 10 2022
medline: 6 10 2022
Statut: ppublish

Résumé

To identify predictors of severe adverse events (≥grade 3) in patients with advanced hepatocellular carcinoma treated with lenvatinib. Of 41 patients, 25 and 16 were stratified into the severe and non-severe adverse events groups, respectively. Of these, 19 formed a lactulose-mannitol test subgroup, which was divided into severe adverse events (n=11) and non-severe adverse events (n=8) groups. Severe adverse events were assessed by liver disease etiology and modified albumin-bilirubin grade. Intestinal permeability by lactulose-mannitol test and serum soluble CD163, soluble mannose receptor, and zonulin levels. Severe adverse event incidence rates were higher in patients with advanced hepatocellular carcinoma related to alcoholic liver disease and nonalcoholic fatty-liver disease than in those with advanced hepatocellular carcinoma of other etiologies (p=0.014). The rates were higher for modified albumin-bilirubin grades 2a and 2b compared to modified albumin-bilirubin grade 1 (p=0.0104). Zonulin levels were higher in the severe adverse event group (p=0.0331) and were independently associated with severe adverse events (odds ratio=140, 95% confidence interval=1.66-11800; p=0.029). Patients with high zonulin levels (≥0.518 ng/ml) experienced more severe adverse events than those with low levels (<0.518 ng/ml) (p=0.0137). In the lactulose-mannitol test subgroup, the urine lactulose:mannitol ratio was higher in the severe vs. non-severe adverse event group (p=0.0164). Moreover, it was higher in patients with alcoholic liver disease and nonalcoholic fatty-liver disease-related advanced hepatocellular carcinoma compared to those with other advanced hepatocellular carcinoma etiologies (p=0.0108). Serum zonulin levels predict severe adverse events in patients with advanced hepatocellular carcinoma treated with lenvatinib.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
To identify predictors of severe adverse events (≥grade 3) in patients with advanced hepatocellular carcinoma treated with lenvatinib.
PATIENTS AND METHODS METHODS
Of 41 patients, 25 and 16 were stratified into the severe and non-severe adverse events groups, respectively. Of these, 19 formed a lactulose-mannitol test subgroup, which was divided into severe adverse events (n=11) and non-severe adverse events (n=8) groups. Severe adverse events were assessed by liver disease etiology and modified albumin-bilirubin grade. Intestinal permeability by lactulose-mannitol test and serum soluble CD163, soluble mannose receptor, and zonulin levels.
RESULTS RESULTS
Severe adverse event incidence rates were higher in patients with advanced hepatocellular carcinoma related to alcoholic liver disease and nonalcoholic fatty-liver disease than in those with advanced hepatocellular carcinoma of other etiologies (p=0.014). The rates were higher for modified albumin-bilirubin grades 2a and 2b compared to modified albumin-bilirubin grade 1 (p=0.0104). Zonulin levels were higher in the severe adverse event group (p=0.0331) and were independently associated with severe adverse events (odds ratio=140, 95% confidence interval=1.66-11800; p=0.029). Patients with high zonulin levels (≥0.518 ng/ml) experienced more severe adverse events than those with low levels (<0.518 ng/ml) (p=0.0137). In the lactulose-mannitol test subgroup, the urine lactulose:mannitol ratio was higher in the severe vs. non-severe adverse event group (p=0.0164). Moreover, it was higher in patients with alcoholic liver disease and nonalcoholic fatty-liver disease-related advanced hepatocellular carcinoma compared to those with other advanced hepatocellular carcinoma etiologies (p=0.0108).
CONCLUSION CONCLUSIONS
Serum zonulin levels predict severe adverse events in patients with advanced hepatocellular carcinoma treated with lenvatinib.

Identifiants

pubmed: 36191983
pii: 42/10/4895
doi: 10.21873/anticanres.15995
doi:

Substances chimiques

Albumins 0
Phenylurea Compounds 0
Quinolines 0
Mannitol 3OWL53L36A
Lactulose 4618-18-2
lenvatinib EE083865G2
Bilirubin RFM9X3LJ49

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4895-4905

Informations de copyright

Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Yuki Fujimoto (Y)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Tadashi Namisaki (T)

Department of Gastroenterology, Nara Medical University, Nara, Japan; tadashin@naramed-u.ac.jp.

Soichi Takeda (S)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Koji Murata (K)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Masahide Enomoto (M)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Hiroaki Takaya (H)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Yuki Tsuji (Y)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Yukihisa Fujinaga (Y)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Yasuhiko Sawada (Y)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Norihisa Nishimura (N)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Koh Kitagawa (K)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Kosuke Kaji (K)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Takashi Inoue (T)

Department of Evidence-Based Medicine, Nara Medical University Hospital, Nara, Japan.

Hideto Kawaratani (H)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Kei Moriya (K)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Takemi Akahane (T)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Akira Mitoro (A)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

Hitoshi Yoshiji (H)

Department of Gastroenterology, Nara Medical University, Nara, Japan.

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Classifications MeSH