Review Article| Volume 54, ISSUE 8, P997-1006, August 2022

Sarcopenia in chronic advanced liver diseases: A sex-oriented analysis of the literature

Published:November 14, 2021DOI:


      Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.


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      1. EASL Clinical Practice Guidelines on nutrition in chronic liver disease.
        J Hepatol. 2019; 70: 172-193
        • Kim H.Y.
        • Jang J.W.
        Sarcopenia in the prognosis of cirrhosis: going beyond the MELD score.
        World J Gastroenterol. 2015; 21 (-4): 7637
        • Vidot H.
        • Kline K.
        • Cheng R.
        • et al.
        The relationship of obesity, nutritional status and muscle wasting in patient assessed for liver transplantation.
        Nutrients. 2019; 11: 2097
        • Bunchorntavakul C.
        • Reddy K.R.
        Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis.
        Aliment Pharmacol Ther. 2020; 51: 64-77
        • Lai J.C.
        • Covinsky K.E.
        • Dodge J.L.
        • et al.
        Development of a novel frailty index to predict mortality in patients with end-stage liver disease.
        Hepatology. 2017; 66: 564-574
        • Dasarathy S.
        • Merli M.
        Sarcopenia from mechanism to diagnosis and treatment in liver disease.
        J Hepatol. 2016; 65: 1232-1244
        • Tsien C.
        • Garber A.
        • Narayanan A.
        • et al.
        Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.
        J Gastroenterol Hepatol. 2014; 29: 1250-1257
        • Tandon P.
        • Ney M.
        • Irwin I.
        • et al.
        Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value.
        Liver Transpl. 2012; 18: 1209-1216
        • Hiroaka A.
        • Abiki T.
        • Okudaira T.
        • et al.
        Muscle atrophy as pre-sarcopenia in Japanese patients with chronic liver disease: competed tomography is useful for evaluation.
        J Gastroeterol. 2015; 50: 1206-1213
        • Gowda C.
        • Compher C.
        • Amorosa V.K.
        • et al.
        Association between chronic hepatitis C virus infection and low muscle mass in US adults.
        J Viral Hepat. 2014; 21: 938-943
        • Carey E.J.
        • Lai J.C.
        • Wang C.W.
        • et al.
        A multicenter study to define sarcopenia in patients with end-stage liver disease.
        Liver Transpl. 2017; 23: 625-633
        • Englesbe M.J.
        • Patel S.P.
        • He K.
        • et al.
        Sarcopenia and mortality after liver transplantation.
        J Am Coll Surg. 2010; 211: 271-278
        • Kuo S.Z.
        • Ahmad M.
        • Dunn M.A.
        • et al.
        Sarcopenia predicts post-transplant mortality in acutely ill men undergoing urgent evaluation and liver transplantation.
        Transplantation. 2019; 103: 2312-2317
        • Shamseer L.
        • Moher D.
        • Clarke M.
        • et al.
        Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.
        BMJ. 2015; 350: g7647
        • Fukui A.
        • Kawabe N.
        • Hashimoto S.
        • et al.
        Skeletal muscle mass depletion in patients with hepatitis C virus infection.
        Eur J Gastroenterol Hepatol. 2019; 31: 59-66
        • Carias S.
        • Castellanos A.L.
        • Vilchez V.
        • et al.
        Nonalcoholic steatohepatitis is strongly associated with sarcopenic obesity in patients with cirrhosis undergoing liver transplant evaluation.
        J Gastroenterol Hepatol. 2016; 31: 628-633
        • Montano-Loza A.J.
        • 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: 126-135
        • Hara N.
        • Iwasa M.
        • Sugimoto R.
        • et al.
        Sarcopenia and sarcopenic obesity are prognostic factors for overall survival in patients with cirrhosis.
        Intern Med. 2016; 55: 863-870
        • Montano-Loza A.J.
        • Meza-Junco J.
        • Baracos V.E.
        • et al.
        Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation.
        Liver Transpl. 2014; 20: 640-648
        • Praktiknjo M.
        • Book M.
        • Luetkens J.
        • et al.
        Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis.
        Hepatology. 2018; 67: 1014-1026
        • Skladany L.
        • Koller T.
        • Molcan P.
        • et al.
        Prognostic usefulness of serum myostatin in advanced chronic liver disease: its relation to gender and correlation with inflammatory status.
        J Physiol Pharmacol. 2019; 70: 357-368
        • Moctezuma-Velázquez C.
        • Low G.
        • Mourtzakis M.
        • et al.
        Association between low testosterone levels and sarcopenia in cirrhosis: a cross-sectional study.
        Ann Hepatol. 2018; 17: 615-623
        • Kang S.H.
        • Jeong W.K.
        • Baik S.K.
        • et al.
        Impact of sarcopenia on prognostic value of cirrhosis: going beyond the hepatic venous pressure gradient and MELD score.
        J Cachexia Sarcopenia Muscle. 2018; 9: 860-870
        • Jeong J.Y.
        • Lim S.
        • Sohn J.H.
        • et al.
        Presence of sarcopenia and its rate of change are independently associated with long-term mortality in patients with liver cirrhosis.
        J Korean Med Sci. 2018; 33: 1-13
        • Nishikawa H.
        • Enomoto H.
        • Ishii A.
        • et al.
        Comparison of prognostic impact between the Child-Pugh score and skeletal muscle mass for patients with liver cirrhosis.
        Nutrients. 2017; 9: 595
        • Nishikawa H.
        • Nishimura T.
        • Enomoto H.
        • et al.
        Impact of virtual touch quantification in acoustic radiation force impulse for skeletal muscle mass loss in chronic liver diseases.
        Nutrients. 2017; 9: 620
        • Montano-Loza A.J.
        • Meza-Junco J.
        • Prado C.M.M.
        • et al.
        Muscle wasting is associated with mortality in patients with cirrhosis.
        Clin Gastroenterol Hepatol. 2012; 10: 166-173
        • Kim G.
        • Kang S.H.
        • Kim M.Y.
        • Baik S.K.
        Prognostic value of sarcopenia in patients with liver cirrhosis: a systematic review and meta-analysis.
        PLoS ONE. 2017; 12: 1-16
        • Sempokuya T.
        • Yokoyama-Arakaki L.
        • Wong L.L.
        • Kalathil S.
        A pilot study of racial differences in the current definition of sarcopenia among liver transplant candidates.
        Hawaii J Health Soc Welf. 2020; 79: 161-167
        • Tandon P.
        • Raman M.
        • Mourtzakis M.
        • Merli M.
        A practical approach to nutritional screening and assessment in cirrhosis.
        Hepatology. 2017; 65: 1044-1057
        • Fujiwara N.
        • Nakagawa H.
        • Kudo Y.
        • et al.
        Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma.
        J Hep. 2015; 63: 131-140
        • Imai K.
        • Takai K.
        • Watanabe S.
        • et al.
        Sarcopenia impairs prognosis of patients with hepatocellular carcinoma: the role of liver functional reserve and tumor-related factors in loss of skeletal muscle volume.
        Nutrients. 2017; 9: 1054
        • Begini P.
        • Gigante E.
        • Antonelli G.
        • et al.
        Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.
        Ann Hepatol. 2017; 16: 107-114
        • Voron T.
        • Tselikas L.
        • Pietrasz D.
        • et al.
        Sarcopenia impacts on short- and long-term results of hepatectomy for hepatocellular carcinoma.
        Ann Surgery. 2015; 261: 1173-1183
        • Itoh S.
        • Shirabe K.
        • Matsumoto Y.
        • et al.
        Effect of body composition on outcomes after hepatic resection for hepatocellular carcinoma.
        Ann Surg Oncol. 2014; 21: 3063-3068
        • Iritani S.
        • Imai K.
        • Takai K.
        • et al.
        Skeletal muscle depletion is an independent prognostic factor for hepatocellular carcinoma.
        J Gastroenterology. 2015; 50: 323-332
        • Levolger S.
        • Van Vledder M.G.
        • Muslem R.
        • et al.
        Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma.
        J Surg Oncol. 2015; 112: 208-213
        • Salman M.A.
        • Omar H.S.E.
        • Mikhail H.M.S.
        Sarcopenia increases 1-year mortality after surgical resection of hepatocellular carcinoma.
        ANZ J Surg. 2020; 90: 781-785
        • Loosen S.H.
        • Schulze-Hagen M.
        • Bruners P.
        • et al.
        Sarcopenia is a negative prognostic factor in patients undergoing transarterial chemoembolization (TACE) for hepatic malignancies.
        Cancers (Basel). 2019; 11: 1503
        • Fujita M.
        • Takahashi A.
        • Hayashi M.
        • et al.
        Skeletal muscle volume loss during transarterial chemoembolization predicts poor prognosis in patients with hepatocellular carcinoma.
        Hepatology Res. 2019; 49: 778-786
        • Kobayashi T.
        • Kawai H.
        • Nakano O.
        • et al.
        Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intraarterial therapies.
        BMC Cancer. 2018; 18: 756
        • Antonelli G.
        • Gigante E.
        • Iavarone M.
        • et al.
        Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment.
        UEG J. 2018; 6: 1039-1048
        • Antoun S.
        • Borget I.
        • Lanoy E.
        Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer.
        Curr Opin Support Palliat Care. 2013; 7: 383-389
        • 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. 2013; 3: 1539-1547
        • Prado C.M.
        • Lieffers J.R.
        • McCargar L.J.
        • et al.
        Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study.
        Lancet Oncol. 2008; 9: 629-635
        • Zhang G.
        • Meng S.
        • Li R.
        • et al.
        Clinical significance of sarcopenia in the treatment of patients with primary hepatic malignancies, a systematic review and meta-analysis.
        Oncotarget. 2017; 8: 102474-102485
        • Chang K.V.
        • Chen J.D.
        • Wu W.T.
        • et al.
        Association between loss of skeletal muscle mass and mortality and tumor recurrence in hepatocellular carcinoma: a systematic review and meta-analysis.
        Liver Cancer. 2018; 7: 90-103
        • Nishikawa H.
        • Nishijima N.
        • Enomoto H.
        • et al.
        Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy.
        Oncol Lett. 2017; 14: 1637-1647
        • Yamashima M.
        • Miyaaki H.
        • Honda T.
        • et al.
        Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib.
        Mol Clin Oncol. 2017; 7: 449-453
        • Hiraoka A.
        • Hirooka M.
        • Koizumi Y.
        • et al.
        Muscle volume loss as a prognostic marker in hepatocellular carcinoma patients treated with sorafenib.
        Hepatol Res. 2017; 47: 558-565
        • Yadav A.
        • Chang Y.H.
        • Carpenter S.
        • et al.
        Relationship between sarcopenia, six-minute walk distance and health-related quality of life in liver transplant candidates.
        Clin Transpl. 2015; 29: 134-141
        • Bhanji R.A.
        • Narayanan P.
        • Moynagh M.R.
        • et al.
        Differing impact of sarcopenia and frailty in nonalcoholic steatohepatitis and alcoholic liver disease.
        Liver Transpl. 2019; 25: 14-24
        • Van Vugt J.L.A.
        • Alferink L.J.M.
        • Buettner S.
        • et al.
        A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: a competing risk analysis in a national cohort.
        J Hepatol. 2018; 68: 707-714
        • Van Vugt J.L.A.
        • Buettner S.
        • Alferink L.J.M.
        • et al.
        Low skeletal muscle mass is associated with increased hospital costs in patients with cirrhosis listed for liver transplantation-a retrospective study.
        Transpl Int. 2018; 31: 165-174
        • Durand F.
        • Buyse S.
        • Francoz C.
        • et al.
        Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography.
        J Hepatol. 2014; 60: 1151-1157
        • D'Arcangelo F.
        • Zanetto A.
        • Aliberti C.
        • et al.
        The impact of sarcopenia on the outcome of patients with cirrhosis with and without hepatocellular carcinoma who undergo liver transplantation.
        Hepatoma Res. 2021; 7: 4
        • Dolgin N.H.
        • Movahedi B.
        • Martins P.N.
        • et al.
        Decade-Long Trends in Liver Transplant Waitlist Removal Due to Illness Severity: the Impact of Centers for Medicare and Medicaid Services Policy.
        J Am Coll Surg. 2016; 222: 1054-1065
        • Nachmany I.
        • Dvorchik I.
        • Devera M.
        • et al.
        A validated model for predicting outcome after liver transplantation: implications on transplanting the extremely sick.
        Transpl Int. 2013; 26: 1108-1115
        • Anastacio L.R.
        • Ferreira L.G.
        • Ribeiro H.S.
        Sarcopenia, obesity and sarcopenic obesity in liver transplantation: a body composition prospective study.
        Brazn Arch Dig Surg. 2019; 32: e1434
        • Golse N.
        • Bucur P.O.
        • Ciacio O.
        • et al.
        A new definition of sarcopenia in patients with cirrhosis undergoing liver transplantation.
        Liver Transpl. 2017; 23: 143-154
        • Kalafateli M.
        • Mantzoukis K.
        • Choi Yau Y.
        • et al.
        Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the model for end-stage liver disease score.
        J Cachexia Sarcopenia Muscle. 2017; 8: 113-121
        • Jeon J.Y.
        • Wang H.J.
        • Ock S.Y.
        • et al.
        Newly developed sarcopenia as a prognostic factor for survival in patients who underwent liver transplantation.
        PLoS ONE. 2015; 10e0143966
        • Underwood P.W.
        • Cron D.C.
        • Terjimanian M.N.
        • et al.
        Sarcopenia and failure to rescue following liver transplantation.
        Clin Transplant. 2015; 29: 1076-1080
        • Bergerson J.T.
        • Lee J.G.
        • Furlan A.
        • et al.
        Liver transplantation arrests and reverses muscle wasting.
        Clin Transplant. 2015; 29: 216-221
        • Lee C.S.
        • Cron D.C.
        • Terjimanian M.N.
        • et al.
        Dorsal muscle group area and surgical outcomes in liver transplantation.
        Clin Transplant. 2014; 28: 1092-1098
        • Tsien C.
        • Garber A.
        • Narayanan A.
        • et al.
        Post-liver transplantation sarcopenia in cirrhosis: a prospective evaluation.
        J Gastroenterol Hepatol. 2014; 29: 1250-1257
        • Dolgin N.H.
        • Smith A.J.
        • Harrington S.G.
        • et al.
        Association between sarcopenia and functional status in liver transplant patients.
        Exp Clin Transplant. 2019; 17: 653-664
        • Krell R.W.
        • Kaul D.R.
        • Martin A.R.
        • et al.
        Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation.
        Liver Transplant. 2013; 19: 1396-1402
        • Schutz T.
        • Hudjetz H.
        • Roske A.E.
        • et al.
        Weight gain in long-term survivors of kidney or liver transplantation–another paradigm of sarcopenic obesity?.
        Nutrition. 2012; 28: 378-383
        • Hussaini S.H.
        • Soo S.
        • Stewart S.P.
        • et al.
        Risk factors for loss of lean body mass after liver transplantation.
        Appl Radiat Isot. 1998; 49: 663-664
        • Merli M.
        • Giusto M.
        • Giannelli V.
        • et al.
        Nutritional status and liver transplantation.
        J Clin Exp Hepatol. 2011; 1: 190-198
        • Plank L.D.
        • Metzger D.J.
        • McCall J.L.
        • et al.
        Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery.
        Ann Surg. 2001; 234: 245-255
        • Wagner D.
        • Adunka C.
        • Kniepeiss D.
        • et al.
        Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.
        Clin Transplant. 2011; 25: E396-E400
        • Pinto Dos Santos D.
        • Kloeckner R.
        • Koch S.
        • et al.
        Sarcopenia as prognostic factor for survival after orthotopic liver transplantation.
        Eur J Gastroenterol Hepatol. 2020; 32: 626-634
        • Hamaguchi Y.
        • Kaido T.
        • Okumura S.
        • et al.
        Impact of quality as well as quantity of skeletal muscle on outcomes after liver transplantation.
        Liver Transplantn. 2014; 20: 1413-1419
        • Dasarathy S.
        Post-transplant sarcopenia: an underrecognized early consequence of liver transplantation.
        Dig Dis Sci. 2013; 58: 3103-3111