Reduced handgrip strength is predictive of poor survival among patients with liver cirrhosis: A sex-stratified analysis
Tatsunori Hanai
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Division for Regional Cancer Control, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorCorresponding Author
Makoto Shiraki
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Correspondence: Dr Makoto Shiraki, Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Email: [email protected]Search for more papers by this authorKenji Imai
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorAtsushi Suetsugu
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorKoji Takai
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Division for Regional Cancer Control, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorHisataka Moriwaki
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorMasahito Shimizu
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorTatsunori Hanai
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Division for Regional Cancer Control, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorCorresponding Author
Makoto Shiraki
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Correspondence: Dr Makoto Shiraki, Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Email: [email protected]Search for more papers by this authorKenji Imai
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorAtsushi Suetsugu
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorKoji Takai
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Division for Regional Cancer Control, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorHisataka Moriwaki
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorMasahito Shimizu
Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorConflict of interest: The authors have no conflict of interest.
Financial support: This work was supported by a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (KAKENHI Grant No. 16 K09352).
Abstract
Aim
Handgrip strength (HGS) is a marker of sarcopenia and has been used to stratify an individual's risk of death. We aimed to assess the prognostic significance of HGS in patients with liver cirrhosis.
Methods
In this retrospective study, we collated data of 563 consecutive patients admitted to our hospital with cirrhosis (375 men). A dynamometer was used to measure HGS. Body composition (including skeletal muscle and adipose tissue volumes) was estimated using computed tomography. Predictors of mortality were identified using sex-stratified multivariate analyses.
Results
After adjustments for age, cirrhosis etiology, Child–Pugh score, and other confounding variables, HGS, but not body composition, was independently associated with mortality in male patients (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94–0.99; P < 0.01) and female patients (HR, 0.91; 95% CI, 0.84–0.99; P = 0.02). Men with low HGS (<30 kg) had a higher risk of mortality (HR, 2.09; 95% CI, 1.39–3.17; P < 0.001), as did women with low (<15 kg) HGS (HR, 2.14; 95% CI, 1.16–4.01; P = 0.02). We could stratify the sex-specific risk of mortality in cirrhotic patients using HGS, regardless of coexistent hepatocellular carcinoma and the Child–Pugh class.
Conclusions
Reduced HGS, rather than skeletal muscle and adipose tissue volumes, is associated with an increased risk of mortality in patients of both sexes with liver cirrhosis. Measurement of HGS is a simple, cost-effective, and appropriate bedside assessment for the prediction of survival in patients with cirrhosis.
Supporting Information
| Filename | Description |
|---|---|
| hepr13420-sup-0001-supp_ts1.docxWord 2007 document , 20 KB |
Table S1. Clinical characteristics of cirrhotic patients with hepatocellular carcinoma. |
| hepr13420-sup-0002-supp_ts2.docxWord 2007 document , 23.4 KB |
Table S2. Clinical characteristics of cirrhotic patients based on the criteria for sarcopenia defined by the Japan Society of Hepatology. |
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.
REFERENCES
- 1 European Association for the Study of the Liver. EASL clinical practice guidelines on nutrition in chronic liver disease. J Hepatol 2019; 70: 172–193.
- 2Montano-Loza AJ, Meza-Junco J, Prado CM et al. Muscle wasting is associated with mortality in patients with cirrhosis. Clin Gastroenterol Hepatol 2012; 10: 166–173.
- 3Hanai T, Shiraki M, Nishimura K et al. Sarcopenia impairs prognosis of patients with liver cirrhosis. Nutrition 2015; 31: 193–199.
- 4Nishikawa H, Shiraki M, Hiramatsu A, Moriya K, Hino K, Nishiguchi S. 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 2016; 46: 951–963.
- 5Wind AE, Takken T, Helders PJ et al. Is grip strength a predictor for total muscle strength in healthy children, adolescents, and young adults? Eur J Pediatr 2010; 169: 281–287.
- 6Flood A, Chung A, Parker H, Kearns V, O'Sullivan TA. The use of hand grip strength as a predictor of nutrition status in hospital patients. Clin Nutr 2014; 33: 106–114.
- 7Leong DP, Teo KK, Rangarajan S et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet 2015; 386: 266–273.
- 8Cooper R, Kuh D, Hardy R et al. Objectively measured physical capability levels and mortality: systematic review and meta-analysis. BMJ 2010; 341: 4467.
- 9Bohannon RW. Hand-grip dynamometry predicts future outcomes in aging adults. J Geriatr Phys Ther 2008; 31: 3–10.
- 10Sharma P, Rauf A, Matin A, Agarwal R, Tyagi P, Arora A. Handgrip strength as an important bed side tool to assess malnutrition in patient with liver disease. J Clin Exp Hepatol 2017; 7: 16–22.
- 11Ye Q, Yin W, Zhang L et al. The value of grip test, lysophosphatidlycholines, glycerophosphocholine, ornithine, glucuronic acid decrement in assessment of nutritional and metabolic characteristics in hepatitis B cirrhosis. PLoS One 2017; 12: 0175165.
- 12McDaniel J, Davuluri G, Hill EA et al. Hyperammonemia results in reduced muscle function independent of muscle mass. Am J Physiol Gastrointest Liver Physiol 2016; 310: 163–170.
- 13Alvares-da-Silva MR, Reverbel da Silveira T. Comparison between handgrip strength, subjective global assessment, and prognostic nutritional index in assessing malnutrition and predicting clinical outcome in cirrhotic outpatients. Nutrition 2005; 21: 113–117.
- 14Lai JC, Covinsky KE, Dodge JL et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology 2017; 66: 564–574.
- 15Tapper EB, Konerman M, Murphy S, Sonnenday CJ. Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index. Am J Transplant 2018; 18: 2566–2570.
- 16Plank LD, Gane EJ, Peng S et al. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology 2008; 48: 557–566.
- 17Peng S, Plank LD, McCall JL et al. Body composition, muscle function, and energy expenditure in patients with liver cirrhosis: a comprehensive study. Am J Clin Nutr 2007; 85: 1257–1266.
- 18Belarmino G, Gonzalez MC, Torrinhas RS et al. Phase angle obtained by bioelectrical impedance analysis independently predicts mortality in patients with cirrhosis. World J Hepatol 2017; 9: 401–408.
- 19Carey EJ, Lai JC, Wang CW et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl 2017; 23: 625–633.
- 20Caregaro L, Alberino F, Amodio P et al. Malnutrition in alcoholic and virus-related cirrhosis. Am J Clin Nutr 1996; 63: 602–609.
- 21Ebadi M, Tandon P, Moctezuma-Velazquez C et al. Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis. J Hepatol 2018; 69: 608–616.
- 22Fujiwara N, Nakagawa H, Kudo Y et al. Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J Hepatol 2015; 63: 131–140.
- 23Iritani S, Imai K, Takai K et al. Skeletal muscle depletion is an independent prognostic factor for hepatocellular carcinoma. J Gastroenterol 2015; 50: 323–332.
- 24Newman AB, Kupelian V, Visser M et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci 2006; 61: 72–77.
- 25Fukui H, Saito H, Ueno Y et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol 2016; 51: 629–650.
- 26Kokudo N, Hasegawa K, Akahane M et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res 2015; 45: 2.
- 27Kudo M, Matsui O, Izumi N et al. JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan. Liver Cancer 2014; 3: 458–468.
- 28Shen W, Punyanitya M, Wang Z et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol (1985) 2004; 97: 2333–2338.
- 29Mitsiopoulos N, Baumgartner RN, Heymsfield SB et al. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol (1985) 1998; 85: 115–122.
- 30Youden WJ. Index for rating diagnostic tests. Cancer 1950; 3: 32–35.
10.1002/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3 CAS PubMed Web of Science® Google Scholar
- 31Wang CW, Feng S, Covinsky KE et al. A comparison of muscle function, mass, and quality in liver transplant candidates: results from the functional assessment in liver transplantation study. Transplantation 2016; 100: 1692–1698.
- 32Mitchell WK, Williams J, Atherton P et al. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol 2012; 3: 260.
- 33Qiu J, Tsien C, Thapalaya S et al. Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 2012; 303: 983–993.
- 34Qiu J, Thapaliya S, Runkana A et al. Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB-mediated mechanism. Proc Natl Acad Sci USA 2013; 110: 18162–18167.
- 35Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci 2012; 67: 28–40.
- 36Kumar A, Davuluri G, Silva RNE et al. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology 2017; 65: 2045–2058.
- 37Dasarathy S. Cause and management of muscle wasting in chronic liver disease. Curr Opin Gastroenterol 2016; 32: 159–165.
- 38Li F, Li Y, Duan Y, Hu CAA, Tang Y, Yin Y. Myokines and adipokines: involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine Growth Factor Rev 2017; 33: 73–82.
- 39Reza MM, Subramaniyam N, Sim CM et al. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy. Nat Commun 2017; 8: 1104.
- 40Nishikawa H, Enomoto H, Ishii A etal. Elevated serum myostatin level is associated with worse survival in patients with liver cirrhosis. J Cachexia Sarcopenia Muscle 2017; 8: 915–925.
- 41Rachakonda V, Borhani AA, Dunn MA etal. Serum leptin is a biomarker of malnutrition in decompensated cirrhosis. PLoS One 2016; 11: 0159142.
- 42Karagozian R, Bhardwaj G, Wakefield DB, Baffy G. Obesity paradox in advanced liver disease: obesity is associated with lower mortality in hospitalized patients with cirrhosis. Liver Int 2016; 36: 1450–1456.
- 43Alberino F, Gatta A, Amodio P etal. Nutrition and survival in patients with liver cirrhosis. Nutrition 2001; 17: 445–450.
- 44Ordan MA, Mazza C, Barbe C etal. Feasibility of systematic handgrip strength testing in digestive cancer patients treated with chemotherapy: the FIGHTDIGO study. Cancer 2018; 124: 1501–1506.
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