Work

Sarcopenia and sarcopenic obesity in patients awaiting liver transplantation

Year: 2023

Type: article

Abstract: Sarcopenia includes the presence of both low skeletal muscle mass and low skeletal muscle function (strength and/or physical performance). A consensus definition of sarcopenia in cirrhosis patients is the phenotypic manifestation of the loss of muscle mass.1 On the basis of body composition analyses, sarcopenic obesity (SO) is defined as a combination of obesity and sarcopenia.2 Sarcopenia and SO have been detected associating with poor prognosis, including frailty, poor survival, infection, and a greater length of hospital stay, physical impairment, and mortality.3 Patients with end-stage liver disease have reduced energy metabolism and protein synthesis. This causes muscle depletion and increases the risk of sarcopenia. Liver transplantation (LT) remains the curative treatment for patients with end-stage liver disease and is associated with mortality, failure to rescue, increased length of hospital and intensive care unit stay, posttransplantation infection, or the occurrence of sepsis.4 Sarcopenia is considered a new predictor of nutritional risk under complicated clinical conditions. However, the model for end-stage liver disease (MELD) and Child–Turcotte–Pugh (CTP) scoring systems do not include nutritional evaluation and physical function of patients.5 Therefore, this study aimed to systematically examine the relationship between end-stage liver disease, sarcopenia, and SO in patients awaiting LT. We retrospectively analyzed 101 patients awaiting LT due to end-stage liver disease (including liver cirrhosis, liver failure, and hepatic carcinoma) at our institution between June 2015 and September 2020 (group L). To confirm whether patients had hepatocellular carcinoma (HCC), we adopted the diagnostic criteria of the 2019 HCC Guidelines in China.6 Because stomach function includes digestion and absorption, it can affect the nutritional condition. Nutritional intake can be influenced by the digestive tract function after gastrointestinal surgery. To compare the prevalence rates of sarcopenia and SO between patients with end-stage liver disease and those with digestive tract cancer, gastric cancer (GC) was selected as the control group. The GC group (group G, n = 101) was matched for gender and age (±2 years) in a 1:1 ratio with group L. The healthy control group (group H) included 51 patients. The inclusion criteria of group L were as follows: (1) Patients with end-stage liver disease based on clinical, laboratory, or radiological findings, with indications for LT including liver failure, hepatic carcinoma, and without responses to any medical treatment; (2) All patients underwent LT at our hospital and computed tomography (CT) scans before they received LT; and (3) Laboratory parameters were acquired before LT. The diagnostic criteria for GC were determined according to pathology. All patients who underwent gastrointestinal surgery during the same period at our hospital were in stage II or III according to the TNM stage. All the patients in the group G underwent CT scans. Group H included individuals who visited our hospital for a physical check-up during the same period and underwent a CT scan. None of the CT reports in group H showed any performance with respect to chronic or malignant diseases. The exclusion criteria for all groups were as follows: lack of CT scan and/or inability to calculate skeletal muscle mass index (SMI) and missing laboratory parameters. This study was approved by our Institutional Review Board (No. QYFYWZLL 26535). Demographic information included sex, age, weight, height, and body mass index (BMI). The laboratory data of group L included serum albumin, bilirubin, serum creatinine, and international normalized ratio (INR). CTP and MELD scores were also collected. All patients received clinical scales and scores, including NRS2002,7 CTP scores, and MELD scores. Sarcopenia was defined as SMI, which is the ratio of lean tissue area to body height. The lean tissue area was equal to the skeletal muscle mass area (SMA) calculated using CT at the level of the third lumbar vertebra (L3). The formula for SMI is as follows: SMI (cm2 m–2) = SMA (cm2)/height2 (m2). Sarcopenia was defined as an SMI less than 52.4 cm2 m–2 for males and less than 38.5 cm2 m–2 for females.8 On CT images, skeletal muscle was identified and quantified using Hounsfield unit (HU) thresholds of −29 to +150. The muscles in the L3 region encompass the psoas, erector spinae, quadratus lumborum, transversus abdominis, external and internal obliques, and rectus abdominis (Supplementary Figure 1A). CT scans can compute cross-sectional areas (cm2) and can easily calculate the proportions of tissue, such as muscle, fat, and skeletal tissue, by summing tissue pixels and multiplying by pixel surface area. Visceral fat area (VFA) was calculated by a trained radiologist using the specific software, with the umbilical horizontal plane (excluding bowel content) as the area with a CT attenuation value in the range of −150 to −50 HU (Supplementary Figure 1B). The subcutaneous fat area (SFA) was defined as the subcutaneous area with HU in the range of −190 to −30 HU9 (Supplementary Figure 1C). Diagnostic criteria for obesity are: Obesity 1 (O1), BMI >25 kg m–2; obesity 2 (O2), VFA > 103 cm2 in men, and VFA >69 cm2 in women.10 According to the diagnostic criteria, the patients were divided into four groups for comparative analysis: the SO, sarcopenia without obesity (SN), obesity without sarcopenia (NO), and nonsarcopenia with nonobesity (NN) groups (Supplementary Table 1). Continuous variables were reported as mean ± standard deviation. Categorical variables were presented as frequencies or percentages. Continuous data were analyzed using one-way analysis of variance with specific intergroup comparisons. A p < 0.05 was considered significant. All statistical analyses were performed using SPSS software (version 26.0; International Business Machines Corp.). This retrospective study involved 139 patients. Among them, 101 patients had available CT scans taken within a month from the transplantation date, and they were designated as group L. Moreover, groups G and L comprised 101 and 51 patients, respectively. The baseline characteristics of 253 patients are summarized in Supplementary Table 2. There were 80 patients with sarcopenia as defined using SMI in group L (79.21%), which was significantly higher than that in groups G (n = 57, 56.4%, p < 0.01) and H (n = 20, 39.2%, p < 0.01). VFA was significantly lower in group L than in groups G (p < 0.01) and H (p < 0.01). In contrast, the SFA was higher in group L than in groups L and H, but the difference was not statistically significant, suggesting more severe visceral fat consumption and increased subcutaneous fat accumulation in patients with end-stage liver disease (Table 1). According to the frequency of sarcopenia, the patients with end-stage liver disease (n = 101) were divided into the sarcopenia group (n = 80) and the nonsarcopenia group (n = 21) for comparative analysis. The number of patients with diabetes in the sarcopenia group was higher than that in the nonsarcopenia group (p < 0.05). The bilirubin level was higher in the sarcopenia group (p < 0.05). The CTP scores also differed between the two subgroups, suggesting poor liver function in patients with sarcopenia (Table 2). The SO, SN, NO, and NN groups comprised 21, 59, 11, and 10 patients, respectively (Table 3). Triglycerides were significantly higher in the SO group than in the other groups (p < 0.01). The MELD score in the SO group was significantly higher than those in the SN (p < 0.01) and the NN (p < 0.01) groups (Supplementary Figure 2). LT is the only definitive treatment for end-stage liver disease. Sarcopenia is more common in patients with end-stage liver disease than in the general population. Its prevalence can range from 30% to 70%.11 Many factors have recently been identified as predictors of post-LT survival and complications. Sarcopenia is an independent predictor of mortality in patients with pre-LT and post-LT, as it is associated with poor liver function, infection, hepatic encephalopathy, reduced quality of life, prolonged hospital stays, and increased healthcare costs.12 According to our results, the risk of sarcopenia is higher in patients awaiting LT (79.2%). The mechanism by which end-stage liver disease leads to sarcopenia may be multifaceted. It may involve decreases in nutrition intake, metabolic disorders, dyspepsia, malabsorption, fasting state, infection, increased muscle protein breakdown, lower protein synthesis, and low levels of anabolic hormones. The activation of the ubiquitin-proteasome system and impaired mitochondrial function also play important roles in muscle wasting. The driving factors of sarcopenia may be associated with a metabolic disorder. Skeletal muscles secrete many cytokines and peptides that can affect muscle synthesis and breakdown.13 Although aging is a recognized risk factor for sarcopenia, it was not found to be related to sarcopenia in our study. The CTP or MELD score is mainly used in clinical practice to evaluate liver function and prognosis. Increased ammonia concentrations and decreased muscle mass are related to the pathogenesis of both covert and overt hepatic encephalopathy in patients with end-stage liver disease. A recent study recognized the role of obesity in the development of symptoms of clinical decompensation; namely, well-nourished patients with a higher prevalence of muscle wasting are more likely to experience hepatic encephalopathy.14 The patients with concurrent sarcopenia and obesity, defined as “sarcopenic obesity,” had a higher risk of physical disability and poor prognosis than patients with only sarcopenia or obesity. We found that blood glucose and triglycerides in the group sarcopenia with obesity were higher than those in other groups. Although it is not significant, it still indicates that SO may lead to an increase in insulin resistance and a decrease in skeletal muscle mass.15 However, our study had some limitations. First, it had a small sample size and was a single-center study. Second, although according to some reviews and consensus, most studies defined sarcopenia as the phenotypic manifestation of loss of muscle mass, it is still better to evaluate the muscle strength in the enrolled patients. Third, it is still a controversial problem to evaluate the sequence of poor liver function versus sarcopenia. A more comprehensive assessment of sarcopenia and more specific assessment tools should be used in future prospective investigations. In our study, the risk of sarcopenia or SO was higher in patients with end-stage liver disease awaiting LT than in those with GC. Sarcopenia was also more common in this patient group. SO is often associated with metabolic abnormalities. Sarcopenia was more common in patients waiting for LT; this may remind doctors to give nutrition intervention to patients in the perioperative period. Acquisition of data: Liang Fang, Xuechun Liu, and Lingyun Zhang. Analysis and interpretation of data: Liang Fang and Xue Jing. Drafting of the manuscript: Liang Fang and Xuechun Liu. Critical revision of the manuscript for important intellectual content: Zibin Tian, Yueping Jiang, and Xueli Ding. Administrative, technical, or material support, and study supervision: Xue Jing. Study concept and design: Xue Jing. None. The authors declare no conflict of interest. This work was supported by grants from the National Natural Science Foundation of Shandong Province (No. ZR202103040311). The study protocol was approved by the Ethics Board of the Affiliated Hospital of Qingdao University (No. QYFYWZLL26535). The patients/participants provided their written informed consent to participate in this study. All data are available upon request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Source: Portal hypertension & cirrhosis

DOI: 10.1002/poh2.52