Our current study investigated how the 5-year survival rate differed between young and older patients, as well as between patients with and without sarcopenia. Our main finding was that older patients had a significant higher malnutrition rate, and decreased L3-SMI, MAMC, and grip strength. The 5-year mortality in older patients was significantly higher than that in young patients (42.2% vs 26.6%). Moreover, patients with sarcopenia were associated with a worse 5-year survival rate than patients without sarcopenia, and this effect was especially evident in older patients. Specifically, patients with sarcopenia aged 65 and over showed a 5-year survival rate of only 20.7%, while the 5-year survival rate reached 61.8% in their young counterparts. Further, of all 320 patients, the effect of sarcopenia on the 5-year survival rate was more prominent in patients with a Child-Pugh score ≥ 9 (36%). For older patients, the effect of sarcopenia on 5-year survival rate was more obvious in the patients with Child-Pugh score ≥ 7.
Convergent studies have revealed the significant role of nutritional status in the prognosis of liver cirrhosis, however, it is frequently overlooked as the nutritional assessment could be complex in liver cirrhosis patients with ascites and/or overweight. Moreover, evidence from clinical practice suggests that malnutrition is a potentially treatable factor for patients with liver cirrhosis. In this regard, it is essential to assess the nutritional status before conducting any nutritional intervention accurately.[28] In the current study, we included three common indicators including L3-SMI, MAMC, and grip strength to assess patients’ muscle quality and strength. Practically, patients with liver cirrhosis usually undergo regular abdominal CT examination to determine the liver morphology and exclude the presence of liver cancer. This provides a great opportunity for assessing the nutritional status with L3-SMI, which can be easily derived from abdominal CT. Given its high predictability for multiple clinical outcomes, the use of L3-SMI may afford promising potentials in sarcopenia diagnosis and long-term prognosis. [29, 30]
The process of aging is associated with a progressive loss in skeletal muscle mass, which is also known as sarcopenia.[31] The European Working Group on Sarcopenia in Older People 2 (EWGSOP2) defines sarcopenia as reduced muscle strength including reduced muscle quantity or quality.[32] It is estimated that adults tend to lose approximate 50% of their muscle mass from the age of 50 to 85, which is predominantly a result of the loss of type II muscle fibers. [33] Previous studies have shown that L3-SMI can be leveraged as an important tool for diagnosing sarcopenia,[34] which represents a risk factor for poor prognosis in patients with liver cirrhosis. [35, 36] Findings from our current study implied that this phenomenon is more prominent in older patients in relative to their young counterparts. Specifically, sarcopenia appeared to exert a significant impact on the 5-year survival among cirrhotic patients aged 65 years and over, and especially for those with a Child-Pugh score ≥ 7. Regarding these results, we can posit that sarcopenia may help explain why some older patients without sarcopenia have a better prognosis and longer survival.
Many factors can help contribute to sarcopenia. [11] Due to insufficient glycogen storage, amino acids frequently act as an alternative energy source in liver cirrhosis patients. This energy generation pattern promotes the breakdown in skeletal muscle, and eventually results in the emergence of sarcopenia.[37] Hyperammonemia, commonly seen in the cirrhosis, is another potential contributor to sarcopenia, where skeletal muscle exerts a compensatory effect on ammonia metabolism and clearance with a decrease in muscle protein synthesis. [38, 39] In addition, decreased appetite and food intake due to abdominal distension, impaired gastrointestinal motility, and reduced levels of testosterone, growth hormones or branched chain amino acid (BCAA) can lead to muscle atrophy. [40, 41]Moreover, the decline of physical function, loss of appetite and gastrointestinal motility are more prominent in older patients with liver cirrhosis, which may be the reason why sarcopenia has a more obvious impact on the prognosis of older patients. Differences in the myogenic regulatory factors (MRFs) between young and older patients could also be crucial mechanisms behind differences in muscle mass and strength, and in response to resistance training and deconditioning.[42]
In addition, the severity of liver disease can also constitute a potential factor affecting the prognosis of cirrhotic patients. Accordingly, we found that the adverse effect of sarcopenia on the prognosis is more obvious in patients with Child-Pugh scores > 9. Furthermore, for older patients, the adverse effect of sarcopenia on prognosis can only be seen in patients with Child-Pugh ≥ 7, but not in those with Child-Pugh < 7. Patients with liver cirrhosis are often accompanied by malnutrition. Once they are complicated with sarcopenia, the prognosis will become worse. At present, etiological treatments (such as swear off drinking, anti-virus treatment, etc.) can effectively slow the progression of liver diseases in many cirrhotic patient. However, once the cirrhosis was complicated with sarcopenia, most patient would experience worse long-term prognosis. [7, 15, 43] For older patients, muscle attenuation is a natural result accompanying the aging process, during which the presence of either liver function deterioration or sarcopenia will greatly affect the 5-year survival. Existing evidence implied that it is possible to improve the prognosis by improving the nutritional status and slowing down the process of sarcopenia in patients with liver cirrhosis, especially for the elderly. [28]
Some potential limitations of this study should be acknowledged. First, this study was based on a retrospective design, with possible selection bias.[5] Moreover, some crucial information may be absent from the medical record. However, the current study may have crucial implications for the clinical management of older cirrhotic patients with sarcopenia, in light of that no studies have hitherto reported on the association between sarcopenia and 5-year survival rate in older patients with liver cirrhosis. Second, the L3-SMI can only be used for evaluating muscle mass. Nevertheless, the evaluation of other healthy measurements like skeletal muscle strength and physical performance (e.g., chair stand test and gait speed) is equally important. [44, 45] In this study, we chose L3-SMI as the primary measure because an abdominal CT is usually a routine examination for patients with liver cirrhosis, and the calculation of L3-SMI is relatively objective and accurate.[46] Therefore, L3-SMI is less likely to be affected by subjective factors and can be used to detect dynamic changes of patients’ nutritional status easily. Future studies are warranted to investigate the effect of nutritional intervention on sarcopenia in cirrhotic patients and to test whether the improvement in nutritional status can benefit the long-term prognosis.