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14-07-2024 | Sarcopenia | Original Article

Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma

Authors: Zhaoxian Li, Yumeng Zhao, Yan Xie, Li Zhang, Yanyan Sun, Kai Yang, Shaoxian Duan, Xinghui Yu, Zhongyang Shen, Wentao Jiang

Published in: Hepatology International

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Abstract

Background

The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear.

Methods

Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT.

Results

Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3 months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83–0.98], C-statistic: 0.78, p = 0.009). Pearson’s correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16 mmol/L decrease in HDL-C and a 0.18 g/L decrease in ApoA1.

Conclusion

Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.
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Literature
1.
go back to reference Marasco G, Serenari M, Renzulli M, et al. Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments. J Gastroenterol. 2020;55(10):927–943CrossRefPubMedPubMedCentral Marasco G, Serenari M, Renzulli M, et al. Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments. J Gastroenterol. 2020;55(10):927–943CrossRefPubMedPubMedCentral
2.
go back to reference Kim YR, Park S, Han S, et al. Sarcopenia as a predictor of post-transplant tumor recurrence after living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Sci Rep. 2018;8(1):7157CrossRefPubMedPubMedCentral Kim YR, Park S, Han S, et al. Sarcopenia as a predictor of post-transplant tumor recurrence after living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Sci Rep. 2018;8(1):7157CrossRefPubMedPubMedCentral
3.
go back to reference Grąt K, Pacho R, Grąt M, et al. Impact of body composition on the risk of hepatocellular carcinoma recurrence after liver transplantation. J Clin Med. 2019;8(10):1672CrossRefPubMedPubMedCentral Grąt K, Pacho R, Grąt M, et al. Impact of body composition on the risk of hepatocellular carcinoma recurrence after liver transplantation. J Clin Med. 2019;8(10):1672CrossRefPubMedPubMedCentral
4.
go back to reference Beumer BR, van Vugt JLA, Sapisochin G, et al. Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria. J Cachexia Sarcopenia Muscle. 2022;13(5):2373–2382CrossRefPubMedPubMedCentral Beumer BR, van Vugt JLA, Sapisochin G, et al. Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria. J Cachexia Sarcopenia Muscle. 2022;13(5):2373–2382CrossRefPubMedPubMedCentral
5.
go back to reference Tantai X, Liu Y, Yeo YH, et al. Effect of sarcopenia on survival in patients with cirrhosis: a meta-analysis. J Hepatol. 2022;76(3):588–599CrossRefPubMed Tantai X, Liu Y, Yeo YH, et al. Effect of sarcopenia on survival in patients with cirrhosis: a meta-analysis. J Hepatol. 2022;76(3):588–599CrossRefPubMed
6.
go back to reference Shafaat O, Liu Y, Jackson KR, et al. Association between abdominal CT measurements of body composition before deceased donor liver transplant with posttransplant outcomes. Radiology. 2023;306(3): e212403CrossRefPubMed Shafaat O, Liu Y, Jackson KR, et al. Association between abdominal CT measurements of body composition before deceased donor liver transplant with posttransplant outcomes. Radiology. 2023;306(3): e212403CrossRefPubMed
7.
go back to reference Richter-Stretton GL, Fenning AS, Vella RK. Skeletal muscle—a bystander or influencer of metabolic syndrome? Diabetes Metab Syndr. 2020;14(5):867–875CrossRefPubMed Richter-Stretton GL, Fenning AS, Vella RK. Skeletal muscle—a bystander or influencer of metabolic syndrome? Diabetes Metab Syndr. 2020;14(5):867–875CrossRefPubMed
8.
go back to reference Lipina C, Hundal HS. Lipid modulation of skeletal muscle mass and function. J Cachexia Sarcopenia Muscle. 2017;8(2):190–201CrossRefPubMed Lipina C, Hundal HS. Lipid modulation of skeletal muscle mass and function. J Cachexia Sarcopenia Muscle. 2017;8(2):190–201CrossRefPubMed
9.
go back to reference Kamath PS, Kim RW. The model for end-stage liver disease (MELD). Hepatology (Baltimore, MD). 2007;45(3):797–805CrossRefPubMed Kamath PS, Kim RW. The model for end-stage liver disease (MELD). Hepatology (Baltimore, MD). 2007;45(3):797–805CrossRefPubMed
10.
go back to reference Nishikawa H, Shiraki M, Hiramatsu A, et al. Japan society of Hepatology guidelines for sarcopenia in liver disease (1st edition): recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res: Off J Japan Soc Hepatol. 2016;46(10):951–963CrossRef Nishikawa H, Shiraki M, Hiramatsu A, et al. Japan society of Hepatology guidelines for sarcopenia in liver disease (1st edition): recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res: Off J Japan Soc Hepatol. 2016;46(10):951–963CrossRef
11.
go back to reference Hamaguchi Y, Kaido T, Okumura S, et al. Proposal for new diagnostic criteria for low skeletal muscle mass based on computed tomography imaging in Asian adults. Nutrition (Burbank, Los Angeles County, Calif). 2016;32(11–12):1200–1205CrossRefPubMed Hamaguchi Y, Kaido T, Okumura S, et al. Proposal for new diagnostic criteria for low skeletal muscle mass based on computed tomography imaging in Asian adults. Nutrition (Burbank, Los Angeles County, Calif). 2016;32(11–12):1200–1205CrossRefPubMed
12.
go back to reference Czigany Z, Kramp W, Bednarsch J, et al. Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2020;20(2):493–503CrossRef Czigany Z, Kramp W, Bednarsch J, et al. Myosteatosis to predict inferior perioperative outcome in patients undergoing orthotopic liver transplantation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2020;20(2):493–503CrossRef
13.
go back to reference Isiklar A, Safer U, Binay Safer V, et al. Impact of sarcopenic obesity on outcomes in patients undergoing living donor liver transplantation. Clin Nutr (Edinburgh, Scotland). 2019;38(2):964–965CrossRef Isiklar A, Safer U, Binay Safer V, et al. Impact of sarcopenic obesity on outcomes in patients undergoing living donor liver transplantation. Clin Nutr (Edinburgh, Scotland). 2019;38(2):964–965CrossRef
14.
go back to reference Molwitz I, Recklies F, Stark M, et al. Muscle quality determined by computed tomography predicts short-term and long-term survival after liver transplantation. Sci Rep. 2023;13(1):7631CrossRefPubMedPubMedCentral Molwitz I, Recklies F, Stark M, et al. Muscle quality determined by computed tomography predicts short-term and long-term survival after liver transplantation. Sci Rep. 2023;13(1):7631CrossRefPubMedPubMedCentral
15.
go back to reference Hsieh YC, Joo SK, Koo BK, et al. Myosteatosis, but not Sarcopenia, Predisposes NAFLD Subjects to Early Steatohepatitis and Fibrosis Progression. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2023;21(2):388–97.e10CrossRef Hsieh YC, Joo SK, Koo BK, et al. Myosteatosis, but not Sarcopenia, Predisposes NAFLD Subjects to Early Steatohepatitis and Fibrosis Progression. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc. 2023;21(2):388–97.e10CrossRef
16.
go back to reference Bhanji RA, Takahashi N, Moynagh MR, et al. The evolution and impact of sarcopenia pre- and post-liver transplantation. Aliment Pharmacol Ther. 2019;49(6):807–813CrossRefPubMed Bhanji RA, Takahashi N, Moynagh MR, et al. The evolution and impact of sarcopenia pre- and post-liver transplantation. Aliment Pharmacol Ther. 2019;49(6):807–813CrossRefPubMed
17.
go back to reference Montano-Loza AJ, Angulo P, Meza-Junco J, et al. Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis. J Cachexia Sarcopenia Muscle. 2016;7(2):126–135CrossRefPubMed Montano-Loza AJ, Angulo P, Meza-Junco J, et al. Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis. J Cachexia Sarcopenia Muscle. 2016;7(2):126–135CrossRefPubMed
18.
go back to reference Kamiliou A, Lekakis V, Chrysavgis L, et al. Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis. Hep Intl. 2024;18(2):688–699CrossRef Kamiliou A, Lekakis V, Chrysavgis L, et al. Prevalence and impact on the outcome of myosteatosis in patients with cirrhosis: a systematic review and meta-analysis. Hep Intl. 2024;18(2):688–699CrossRef
19.
go back to reference Nardelli S, Lattanzi B, Merli M, et al. Muscle alterations are associated with minimal and overt hepatic encephalopathy in patients with liver cirrhosis. Hepatology (Baltimore, MD). 2019;70(5):1704–1713CrossRefPubMed Nardelli S, Lattanzi B, Merli M, et al. Muscle alterations are associated with minimal and overt hepatic encephalopathy in patients with liver cirrhosis. Hepatology (Baltimore, MD). 2019;70(5):1704–1713CrossRefPubMed
20.
go back to reference Montano-Loza AJ, Duarte-Rojo A, Meza-Junco J, et al. Inclusion of sarcopenia within MELD (MELD-Sarcopenia) and the prediction of mortality in patients with cirrhosis. Clin Transl Gastroenterol. 2015;6(7): e102CrossRefPubMedPubMedCentral Montano-Loza AJ, Duarte-Rojo A, Meza-Junco J, et al. Inclusion of sarcopenia within MELD (MELD-Sarcopenia) and the prediction of mortality in patients with cirrhosis. Clin Transl Gastroenterol. 2015;6(7): e102CrossRefPubMedPubMedCentral
21.
go back to reference Lattanzi B, Nardelli S, Pigliacelli A, et al. The additive value of sarcopenia, myosteatosis and hepatic encephalopathy in the predictivity of model for end-stage liver disease. Digestive Liver Dis: Off J Italian Soc Gastroenterol Italian Assoc Study Liver. 2019;51(11):1508–1512CrossRef Lattanzi B, Nardelli S, Pigliacelli A, et al. The additive value of sarcopenia, myosteatosis and hepatic encephalopathy in the predictivity of model for end-stage liver disease. Digestive Liver Dis: Off J Italian Soc Gastroenterol Italian Assoc Study Liver. 2019;51(11):1508–1512CrossRef
22.
go back to reference Linge J, Ekstedt M, Dahlqvist LO. Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD. JHEP Rep: Innov Hepatol. 2021;3(1):100197CrossRef Linge J, Ekstedt M, Dahlqvist LO. Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD. JHEP Rep: Innov Hepatol. 2021;3(1):100197CrossRef
23.
go back to reference Ebadi M, Tsien C, Bhanji RA, et al. Skeletal muscle pathological fat infiltration (Myosteatosis) is associated with higher mortality in patients with cirrhosis. Cells. 2022;11(8):1345CrossRefPubMedPubMedCentral Ebadi M, Tsien C, Bhanji RA, et al. Skeletal muscle pathological fat infiltration (Myosteatosis) is associated with higher mortality in patients with cirrhosis. Cells. 2022;11(8):1345CrossRefPubMedPubMedCentral
24.
go back to reference Hamrick MW, McGee-Lawrence ME, Frechette DM. Fatty infiltration of skeletal muscle: mechanisms and comparisons with bone marrow adiposity. Front Endocrinol. 2016;7:69CrossRef Hamrick MW, McGee-Lawrence ME, Frechette DM. Fatty infiltration of skeletal muscle: mechanisms and comparisons with bone marrow adiposity. Front Endocrinol. 2016;7:69CrossRef
25.
go back to reference Montano-Loza AJ, Meza-Junco J, Baracos VE, et al. Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation. Liver Transpl : Off Publ Am Assoc Study Liver Dis Intl Liver Transpl Soc. 2014;20(6):640–648CrossRef Montano-Loza AJ, Meza-Junco J, Baracos VE, et al. Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation. Liver Transpl : Off Publ Am Assoc Study Liver Dis Intl Liver Transpl Soc. 2014;20(6):640–648CrossRef
26.
go back to reference Ebadi M, Wang CW, Lai JC, et al. Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis. J Cachexia Sarcopenia Muscle. 2018;9(6):1053–1062CrossRefPubMedPubMedCentral Ebadi M, Wang CW, Lai JC, et al. Poor performance of psoas muscle index for identification of patients with higher waitlist mortality risk in cirrhosis. J Cachexia Sarcopenia Muscle. 2018;9(6):1053–1062CrossRefPubMedPubMedCentral
27.
go back to reference Lee JH, Lee HS, Cho AR, et al. Relationship between muscle mass index and LDL cholesterol target levels: analysis of two studies of the Korean population. Atherosclerosis. 2021;325:1–7CrossRefPubMed Lee JH, Lee HS, Cho AR, et al. Relationship between muscle mass index and LDL cholesterol target levels: analysis of two studies of the Korean population. Atherosclerosis. 2021;325:1–7CrossRefPubMed
28.
go back to reference Gong H, Liu Y, Lyu X, et al. Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function. Exp Gerontol. 2022;159: 111668CrossRefPubMed Gong H, Liu Y, Lyu X, et al. Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function. Exp Gerontol. 2022;159: 111668CrossRefPubMed
29.
go back to reference Fu Q, Zhang Z, Hu W, et al. The correlation of triglyceride/high-density lipoprotein cholesterol ratio with muscle mass in type 2 diabetes patients. BMC Endocr Disord. 2023;23(1):93CrossRefPubMedPubMedCentral Fu Q, Zhang Z, Hu W, et al. The correlation of triglyceride/high-density lipoprotein cholesterol ratio with muscle mass in type 2 diabetes patients. BMC Endocr Disord. 2023;23(1):93CrossRefPubMedPubMedCentral
30.
go back to reference Vella CA, Nelson MC, Unkart JT, et al. Skeletal muscle area and density are associated with lipid and lipoprotein cholesterol levels: the multi-ethnic study of atherosclerosis. J Clin Lipidol. 2020;14(1):143–153CrossRefPubMedPubMedCentral Vella CA, Nelson MC, Unkart JT, et al. Skeletal muscle area and density are associated with lipid and lipoprotein cholesterol levels: the multi-ethnic study of atherosclerosis. J Clin Lipidol. 2020;14(1):143–153CrossRefPubMedPubMedCentral
31.
go back to reference Bhullar AS, Anoveros-Barrera A, Dunichand-Hoedl A, et al. Lipid is heterogeneously distributed in muscle and associates with low radiodensity in cancer patients. J Cachexia Sarcopenia Muscle. 2020;11(3):735–747CrossRefPubMedPubMedCentral Bhullar AS, Anoveros-Barrera A, Dunichand-Hoedl A, et al. Lipid is heterogeneously distributed in muscle and associates with low radiodensity in cancer patients. J Cachexia Sarcopenia Muscle. 2020;11(3):735–747CrossRefPubMedPubMedCentral
32.
go back to reference Davuluri G, Allawy A, Thapaliya S, et al. Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress. J Physiol. 2016;594(24):7341–7360CrossRefPubMedPubMedCentral Davuluri G, Allawy A, Thapaliya S, et al. Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress. J Physiol. 2016;594(24):7341–7360CrossRefPubMedPubMedCentral
33.
go back to reference Crudele L, de Matteis C, Piccinin E, et al. Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis. JHEP Rep: Innov Hepatol. 2023;5(1): 100627CrossRef Crudele L, de Matteis C, Piccinin E, et al. Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis. JHEP Rep: Innov Hepatol. 2023;5(1): 100627CrossRef
34.
go back to reference Cho Y, Cho EJ, Yoo JJ, et al. Association between lipid profiles and the incidence of hepatocellular carcinoma: a nationwide population-based study. Cancers. 2021;13(7):1599CrossRefPubMedPubMedCentral Cho Y, Cho EJ, Yoo JJ, et al. Association between lipid profiles and the incidence of hepatocellular carcinoma: a nationwide population-based study. Cancers. 2021;13(7):1599CrossRefPubMedPubMedCentral
35.
go back to reference Martin L, Birdsell L, Macdonald N, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol: Off J Am Soc Clin Oncol. 2013;31(12):1539–1547CrossRef Martin L, Birdsell L, Macdonald N, et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol: Off J Am Soc Clin Oncol. 2013;31(12):1539–1547CrossRef
36.
go back to reference Lundsgaard AM, Kiens B. Gender differences in skeletal muscle substrate metabolism—molecular mechanisms and insulin sensitivity. Front Endocrinol. 2014;5:195CrossRef Lundsgaard AM, Kiens B. Gender differences in skeletal muscle substrate metabolism—molecular mechanisms and insulin sensitivity. Front Endocrinol. 2014;5:195CrossRef
Metadata
Title
Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma
Authors
Zhaoxian Li
Yumeng Zhao
Yan Xie
Li Zhang
Yanyan Sun
Kai Yang
Shaoxian Duan
Xinghui Yu
Zhongyang Shen
Wentao Jiang
Publication date
14-07-2024

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