Lenvatinib or Sorafenib Treatment Causing a Decrease in Skeletal Muscle Mass, an Independent Prognostic Factor in Hepatocellular Carcinoma: A Survival Analysis Using Time-Varying Covariates

SIMPLE SUMMARY: Skeletal muscle depletion is one of the established prognostic factors for hepatocellular carcinoma (HCC). This study clearly demonstrated that skeletal muscle mass continued to decrease significantly during lenvatinib (LEN) or sorafenib (SOR) treatment, which has recently played a major role in the treatment of unresectable HCC. Furthermore, the survival analysis using time-varying covariates in this study revealed that it was one of the independent prognostic factors together with tumor makers and liver functional reserve. These results can help improve the management of unresectable HCC because they suggest that it is essential to prevent skeletal muscle depletion, especially in using LEN/SOR to improve survival in HCC patients. ABSTRACT: This study aimed to assess the effects of lenvatinib (LEN) or sorafenib (SOR) treatment for hepatocellular carcinoma (HCC) on body composition and changes in body composition on survival. This study enrolled 77 HCC patients. Skeletal muscle index (SMI), subcutaneous and visceral adipose tissue indices (SATI and VATI), AFP, PIVKA-II, and ALBI scores were analyzed at the time of LEN/SOR introduction, three months after the introduction, at treatment discontinuation, and the last observational time. The differences between chronological changes in these values were analyzed using a paired t-test. The Cox proportional hazards model was used to analyze prognostic factors using time-varying covariates. The chronological changes in each factor were 45.5–43.6–40.6–39.8 (cm(2)/m(2)) for SMI, 41.7–41.6–36.3–33.7 (cm(2)/m(2)) for SATI, 41.9–41.1–37.1–34.8 (cm(2)/m(2)) for VATI, 2.379–26.42–33.61–36.32 (×10(3) ng/mL) for AFP, 9.404–13.39–61.34–25.70 (×10(3) mAU/mL) for PIVKA-II, and −2.56–−2.38–−1.99–−1.90 for the ALBI score. The presence of pre-treatment (p = 0.042), AFP (p = 0.002), PIVKA-II (p < 0.001), ALBI score (p < 0.001), and SMI (p = 0.001) were independent prognostic factors. Skeletal muscle mass decreases significantly during LEN/SOR treatment and is an independent prognostic factor for HCC.