## 4 Discussion
A large prospective cohort study and meta-analysis showed that low handgrip strength was significantly associated with the risk of cancer mortality [35; 36]. However, only one study reported on the association between handgrip strength and mortality in patients with LC including HCC; the OS rates were significantly shorter in LC or HCC patients with low handgrip strength than in those with high handgrip strength, and low handgrip strength was independently associated with an increased risk of mortality, rather than skeletal muscle mass [37]. Although HCC patients were included, this report focused on all-cause mortality in LC patients. As previous reports demonstrated that handgrip strength was associated with health-related quality of life and the incidence of composite hepatic events (e.g., hepatic decompensation and HCC, etc.) in patients with chronic liver diseases [38; 39], patients with low handgrip strength might be more likely to experience AEs than those with high handgrip strength. Therefore, low handgrip strength might be also a predictor of AEs in HCC patients treated with lenvatinib. In contrast, a recent study has reported that skeletal muscle depletion was associated with the occurrence of severe AEs, worse TTF, and poor OS in HCC patients treated with lenvatinib [32]. Some differences were noted in the clinical characteristics between our study and the previous study (our study: Child-Pugh B, 20.7%; BCLC stage C, 47.2%; presence of MVI, 20.8%; presence of EHS, 28.3%; presence of muscle depletion, 49.1%; previous study: Child-Pugh B, 28%; BCLC stage C, 51%; presence of MVI, 27%; presence of EHS, 36%; and presence of muscle depletion, 59%); liver function and HCC stage were worse in the previous study compared with those in our study. Consequently, the MST was shorter in the previous study (10.0 months) than in our study (24.0 months). Although skeletal muscle depletion was not an independent prognostic factor in our study, we considered that our result leaves room for reconsideration because of the short follow-up period. In addition, a long follow-up period is required. Sarcopenia based on the JSH diagnostic guideline was associated with worse TTF and poor OS. Thus, it is possible to narrow the range of poor clinical outcome by means of this diagnostic guideline. However, the assessment of skeletal muscle mass using CT or BIA is limited in clinical practice because it is expensive, time-consuming, and involves radiation exposure. Measurement of handgrip strength, which can be performed even when at the bedside, is a simple, rapid, inexpensive assessment tool. Therefore, we considered that handgrip strength has a powerful effect on clinical outcomes of HCC patients treated with lenvatinib in real-world practice. A study reports that cancer rehabilitation was associated with prolonged survival in HCC patients treated with transcatheter arterial chemoembolization (TACE) [40] and cancer rehabilitation might also improve survival for HCC patients with low handgrip strength treated with lenvatinib. Further investigations are required on this topic. This study had several limitations. First, this was a single-center retrospective cohort study assessing a small number of patients. Therefore, further multicenter studies with a larger population are warranted. Second, the follow-up period was short. Patients who discontinue lenvatinib therapy due to AEs or disease progression were treated with post-treatments (13 patients received sorafenibib, then 6 of 13 received regorafenib. Four patients received hepatic arterial infusion chemotherapy and two of the four received sorafenibib). At this time, the effect of these post-treatments on OS may not have been accurately assessed because of the short follow-up period. Moreover, a long follow-up period might draw a different conclusion regarding skeletal muscle mass.