Prognostic Value of Skeletal Muscle Loss in Unresectable Hepatocellular Carcinoma Treated with TACE-Based Combination Therapy

Background/Objectives: Decreases in skeletal muscle mass affect the efficacy of and tumor response to various therapies for hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between changes in skeletal muscle mass during TACE-based combination therapy and tumor response and prognosis. Methods: This retrospective study analyzed 306 patients with unresectable HCC, divided into four groups according to the treatment received: TACE alone (n = 133), TACE plus targeted and immunotherapy combination (TACE + T + I, n = 68), TACE plus immunotherapy (TACE + I, n = 52), and TACE plus targeted therapy (TACE + T, n = 53). Skeletal muscle mass was assessed at the third lumbar vertebral level (L3) before treatment and at six months post-treatment using computed tomography (CT) scans. Patients were stratified based on changes in skeletal muscle index (SMI) values. Kaplan–Meier and Cox proportional hazards models were used to compare overall survival (OS) among groups classified by changes in SMI, while tumor response was assessed with univariate and multivariate analyses, using logistic regression analysis. Result: A total of 306 patients with unresectable HCC were included in this study. The median OS was 17.0 (0.9–83.0) months in the decreased-SMI group compared with 35.0 (2.0–113.0) months in the non-decreased-SMI group. The overall response rate (CR + PR) was 34.7% in the decreased-SMI group and 53.8% in the non-decreased group. Among different treatment regimens, significant differences in Kaplan–Meier survival curves were observed between the TACE and TACE + T + I groups. In multivariate analysis, decreased SMI remained an independent predictor of poor OS and tumor non-response, whereas a low-SMI pre-treatment was not an independent prognostic factor. Additionally, inadequate nutritional status and compromised liver function were associated with a greater decrease in SMI during comprehensive treatment. Conclusions: A decline in skeletal muscle index (SMI) among patients with unresectable hepatocellular carcinoma (HCC) undergoing TACE-based comprehensive treatment is associated with poor prognosis and unfavorable tumor response and is further linked to deteriorating nutritional status and impaired liver function. Monitoring SMI provides an effective approach for assessing overall patient condition and predicting clinical outcomes.