Research Article: Effect of body composition on survival benefit of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: A comparison with sorafenib therapy

Date Published: June 13, 2019

Publisher: Public Library of Science

Author(s): Issei Saeki, Takahiro Yamasaki, Masaki Maeda, Takuro Hisanaga, Takuya Iwamoto, Toshihiko Matsumoto, Isao Hidaka, Tsuyoshi Ishikawa, Taro Takami, Isao Sakaida, Gianfranco D. Alpini.


Sorafenib is used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, hepatic arterial infusion chemotherapy (HAIC) has also gained acceptance, but only in Japan. We explored the role of body composition as a factor affecting the survival benefit of HAIC compared to sorafenib for the treatment of advanced HCC.

We conducted a retrospective study using the clinical records of 133 patients with advanced HCC treated either with HAIC or sorafenib. Prior to treatment induction, skeletal muscle index and visceral fat area (VFA) were measured at the third lumbar vertebral and umbilical levels, respectively, using computed tomography. Muscle depletion and high-VFA (H-VFA) were defined using published cut-offs. We analyzed clinical parameters, including body composition as prognostic factors.

In the HAIC group, multivariate analysis identified a positive response to HAIC (hazard ratio [HR], 0.438; p = 0.022), and conversion from HAIC to sorafenib (HR, 0.374; p = 0.008) as favorable prognostic factors for survival. In contrast, tumor number < 7 (HR, 0.475; p = 0.008), absence of extra-hepatic spread (HR, 0.511; p = 0.015), absence of muscle depletion (HR, 0.555; p = 0.044), and H-VFA (HR, 0.483; p = 0.015) were studied in the sorafenib group. Body composition was identified as a prognostic factor for patient survival after treatment with sorafenib, but not for HAIC, and may be used as a biomarker when selecting between HAIC or sorafenib treatment of patients with advanced HCC. Additionally, conversion to sorafenib in patients receiving HAIC could improve survival regardless of response status.

Partial Text

Hepatocellular carcinoma (HCC) is the most common cause of liver cancer and the fourth most frequent cause of death in the world [1]. The number of primary liver cancer cases, of which HCC accounts for 75–85%, is expected to increase globally by 2030 [2]; however, of the 30 modeled countries, only Japan is predicted to decline in liver cancer incidence. In contrast, the number of patients with HCC who test negative for both hepatitis B surface antigen and hepatitis C virus antibody is increasing in Japan [3, 4], which is problematic as these patients are not adequately screened and, therefore, the disease is not diagnosed until it has reached late stages [5]. Furthermore, many patients who have received curative therapies such as surgical resection or local ablation subsequently develop recurrent disease which is often advanced.

JSH recommends administration of HAIC as a first-line treatment for unresectable advanced HCC with portal invasion [10]; however, American or European professional organizations do not recommend it because of lack of evidence of survival benefits [6, 8]. Instead, the latter ones support systemic chemotherapy, including administration of sorafenib, a multi-targeted tyrosine kinase inhibitor (TKI) as a first treatment [6–10]. Therefore, it is necessary to identify patient characteristics that correlate with response to HAIC.