In this retrospective study, the skeletal muscle index of HCC patients experiencing curative hepatectomy plus adjuvant TACE significantly decreased over 6 months. More skeletal muscle mass loss served as an independent predictor of poor survival for HCC patients.
In advanced HCC patients, low SMI or sarcopenia was more common and proved to have a negative impact on these patients undergoing systemic therapy or intra-arterial therapy[16-18]. Indeed, the incidence of low SMI or sarcopenia in HCC patients who received curative treatments was also high and worthy of attention. In this study, low SMI patients accounted for 37.1% of study subjects, which was similar to 14.0-40.3% reported in previous studies[19-22]. Comparing to distribution of age or sex and the frequency of liver cirrhosis or chronic liver disease among these studies, it seems that the prevalence of low SMI was in accordance with liver disease progression. Besides, the effect of tumor burden led to reduced SMI due to decreasing appetite, increasing protein decomposition and aggravation of systemic inflammatory response[18, 23].
In addition, some prior studies also identified either low SMI or sarcopenia as indicative of recurrence and reduced survival for HCC patients undergoing hepatectomy[19, 24-26]. However, this study indicated that preoperative SMI did not stratify liver-related mortality risk, which could be a result of different endpoint and additional adjuvant TACE treatment.
When the presence of risk factors determined after curative hepatectomy for HCC patients, the combined therapy, namely curative hepatectomy plus adjuvant TACE, is an appropriate therapy. However, there were no studies elucidating the impact of skeletal muscle loss on such patients previously. As an integrated course of treatment aiming to achieve curative effect, skeletal muscle mass depletion should be quantified during a period of combined treatment rather than hepatectomy alone. Hence, the potential impact of TACE on skeletal muscle mass was considered in our study.
Our data showed that the median SML over 6 months was -1.6% in the cohort of patients with Child-Pugh A class. A study found that the annual change rate in skeletal muscle mass at the level of L3 in counterparts was -1.3%. This demonstrated that SML during hepatectomy plus adjuvant TACE was also significant. In a study concerning changes in body composition for HCC patients underwent hepatectomy, the psoas muscle index was measured at different time points after surgery and measurements failed to exceed preoperative level in the following two years. It is surmised that the loss of skeletal muscle mass caused by hepatectomy could last for a quite long time. Notably, skeletal muscle loss varied individually in this study. This could be attributed to the heterogeneity of individual liver function reserve and adjuvant TACE treatment.
Increasing evidence has demonstrated that more skeletal muscle loss may be related to poor tumor characteristics, such as MVI, larger tumor size and worse liver function, but not the treatment itself. Our results showed more skeletal muscle mass loss during treatment was associated with cirrhosis, MVI and inflammatory status, which is in line with the findings of other studies, and a negative correlation was observed between SML and liver cirrhosis as well as MVI. Recently, researchers have found that there was a distinct decrease in skeletal muscle mass per TACE cycle, and the degree of skeletal muscle mass depletion was a risk factor for overall survival[10, 11]. They further proposed that the SML after the first TACE largely reflected worse tumor characteristics, and the liver function reserve was the main factor affecting SML in subsequent TACE cycles. Similarly, a study enrolling HCC patients who underwent radiotherapy to the liver demonstrated that HCC patients newly diagnosed with sarcopenia after radiotherapy had more Child-Pugh B or C as well as a larger tumor burden. Another report including 603 patients with cirrhosis identified a higher NLR level in patients with severe sarcopenia than those in non- and sarcopenic groups. In addition, Voron, T. et al. thought sarcopenia was associated with HCC satellite lesions and MVI.
This study revealed that SML could evidently differentiate survival stratification. In spite of no statistical significance in some subgroups, it is probably related to the limited sample size. In the comparison of SMI, skeletal muscle mass loss and its rate may be more likely to reflect the response of patient’s condition to therapeutic intervention. A cohort study also showed that the rate of muscle loss was a robust predictor for mortality in patients with cirrhosis instead of other single muscle mass-related measurements.
Our results showed that SML<-2.42% remained a significant independent risk factor for reduced CSS, indicating that the effect of skeletal muscle loss on prognosis was not the result of concomitant presence of adverse factors but rather the progression of liver dysfunction and worse general clinical condition. A mounting number of studies have unveiled that skeletal muscle mass loss was associated with pathophysiological alternations in the body, including decreased hepatic glycogen synthesis, hyperammonemia, glycogenolysis, myostatin, autophagy, and proinflammatory cytokines as well as endocrine changes[1, 31, 32]. However, more explorations are required in the underlying mechanisms.
To date, there is only general guidance for the prevention and treatment of sarcopenia，without a distinct role on decision-making in clinical settings. Our study suggested individual skeletal muscle loss and its rate were quite remarkable, especially for HCC patients with cirrhosis. Accordingly, it is necessary to increase awareness of declining skeletal muscle index during radiologic follow-up. If obvious skeletal muscle loss is observed, nutrition- supporting interventions, such as late evening snack, branched-chain amino acid supplementation and in-hospital exercise, should be considered[33-35].
The limitation of this study should be recognized. First, the data were retrospectively collected and analysed from a single center. Second, due to a lack of skeletal muscle function evaluation, sarcopenia could not be defined strictly, but the loss of skeletal muscle mass could be precisely quantified. Third, because of the limited sample size of certain subgroup, some conclusions need to be further validated.