Sarcopenia[1].pptx management in patient of cirrhosis

sarcopenia management

1. Sarcopenia in Liver Diseases 8.1.2019 PGIMER

2. Outline Introduction Pathophysiology Diagnosis Implications Management Conclusion

3. Introduction Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with risk of adverse outcomes such as physical disability, poor quality of life and death Emerged as independent predictor of poor prognosis in cirrhosis as well as reduced survival post LT Frequently unseen and ignored complication

4. Related Terminologies Abnormality Definition Frailty Syndrome defined by diminished strength, endurance, and reduced physiological function that increases vulnerability for developing physical dependency and death Sarcopenia Loss of anatomic muscle mass Malnutrition State resulting from consumption of either inadequate or excessive nutrients including calories, protein, carbohydrates, vitamins, or minerals Cachexia Loss of lean tissue mass involving a loss of greater than 5% of body weight

5. Sarcopenia Loss of skeletal muscle mass Muscle mass two standard deviations below the healthy young adult mean 30–70% of cirrhotic patients Incidence in men slightly higher than in women Alberino F et al Nutrition. 2001 Jun; 17(6)

6. Criteria for diagnosis Criterion 1 plus (criterion 2 or 3)- 1. Low muscle mass 2. Low muscle strength 3. Low physical performance  European consensus on definition and diagnosis- Alfonso J- Age Ageing 2010 Jul; 39(4): 412–423.

7. Staging EWGSOP conceptual stages of sarcopenia Stage Muscle mass Muscle strength Performance Presarcopenia Sarcopenia Or Severe sarcopenia  European consensus on definition and diagnosis- Alfonso J- Age Ageing 2010 Jul; 39(4): 412–423.

8. Pathophysiology Alterations in food intake Hypermetabolism Alteration in amino acid metabolism Endotoxemia Accelerated starvation Decreased mobility

9. Mechanism of sarcopenia Both starvation with impaired muscle protein biosynthesis and simultaneous muscle proteolysis needed for gluconeogenesis Impaired regenerative capacity regulated by muscle satellite cell function Dasarathy S Clin Liver Dis. 2012 Feb; 16(1):95-131.

10. Liver – muscle axis Mediators of cirrhotic sarcopenia - Increased ammonia , deficient testosterone and growth hormone and increased endotoxin Endotoxemia via TNFa dependent and potentially TNF independent pathways may also impair protein synthesis and potentially activate autophagy Qiu J, Tsien C, Am J Physiol Endocrinol Metab . 2012 Oct 15; 303(8)

11. Hyperammonemia 1. Excess ammonia combines with glutamic acid to form glutamine 2.Increased needfor glutamic acid depletes the amino acid pool 3. Glutamic acid formation from a- ketoglutarate depletes citric acid cycle intermediate 4,5- Ammonia triggers formation and release of myostatin 6,7-Ammonia inhibits muscle contractility stimulates muscle lysosomal autophagy

12. Screening All patients with advanced chronic liver disease & in particular patients with decompensated cirrhosis are advised to undergo a rapid nutritional screen Two simple criteria stratify patients at high risk: BMI< 18.5 kg/m2 Advanced decompensated cirrhosis (Child-Pugh C patients)

13. Screening tool Royal Free Hospital-nutritional prioritizing tool (RFH-NPT) score Improvement in RFH-NPT score was associated with improved survival Borhofen et al Dig Dis Sci. 2016 Jun;61(6):1735-43.

14. Assessment of Sarcopenia Variable Research Clinical practice Muscle mass CT MRI DXA( Dual energy X-ray absorptiometry ) BIA( Bioimpedence analysis) BIA DXA Anthropometry Muscle strength Handgrip strength Knee flexion/extension Peak expiratory flow Handgrip strength Physical performance Short Physical Performance Battery (SPPB) Usual gait speed Timed get-up-and-go test Stair climb power test SPPB Usual gait speed Timed get-up-and-go test  European consensus on definition and diagnosis- Alfonso J- Age Ageing 2010 Jul; 39(4): 412–423.

15. Assessment of Sarcopenia CT image analysis at L3 vertebra is almost universally recognised as a specific method to quantify muscle loss Psoas muscle, para spinal and abdominal wall muscles Relatively independent of activity and water retention consistently altered by metabolic & molecular perturbations of cirrhosis

16. SMI Total cross-sectional area (cm2) of abdominal skeletal muscles at L3 Normalised to height to calculate skeletal muscle index (cm2/m2) All measures require normal values that are based on age, gender and ethnicity

17. Recent multicenter study in patients with end-stage liver disease suggested 3rd lumbar vertebral level SMI cut-points of <50 cm2 /m2 for men and <39 cm2/m2 for women based on optimal correlation with survival outcomes Carey EJ- Liver Transpl . 2017;23:625-633. SMI

18. CT images L3 skeletal muscle Index assessment of two patients with cirrhosis (A, B) with identical BMI A: sarcopenic (L3 SMI of 50 cm 2 /m 2 ) B: not sarcopenic (L3 SMI of 71 cm 2 /m 2)

19. Anthropometry Triceps skinfold (TSF) Mid-arm Muscle Circumference(MAMC ) defined as mid-arm circumference minus [triceps skinfold (TSF) x 0.314] Low MAMC was found to be independent predictor of mortality after liver transplant Both MAMC and TSF have demonstrated prognostic value for mortality among cirrhotic patients MAMC having a higher prognostic power than TSF Mid-arm muscular area(MAMA) = (MAMC) 2 /4 x 0.314] Falsely elevated due to fluid overload

20. Bioelectrical impedance analysis (BIA) Involves passage of small AC electrical current through the body Principle- As current is conducted by body water, impedance is inversely related to total body water Cut off- 7.0 kg/m2 in men and 5.7 kg/m2 in women , defined by appendicular skeletal muscle mass/height2 Simple and portable Major drawback- distorted by hydration status and presence of edema

21. BIA Impedance to the electrical flow of an injected current is related to the volume of the conductor (human body) and the square of the length of the conductor (height).

22. Dual-energy X-ray absorptiometry . Height-adjusted skeletal muscle mass cutoff values were 7.0 kg/m2 in men and 5.4 kg/m2 in women by using DXA Appendicular lean mass (APLM) specifically comprises of lean muscle mass of all four limbs from a DXA scan Defined a skeletal muscle mass index (SMI) as APLM/height 2  (kg/m 2 )  Sarcopenia has been defined as an APLM index (APLM/height 2 ) of ≥2 standard deviations below mean of normal APLM index of <4.61 kg/m2 in women and <6.57 kg/m2 in men Baumgartner et al Am J Epidemiol . 1998 Apr 15; 147(8):755-63.

23. Comparision

24. Total Psoas Area

25. Hand Grip test Can be quantified by measuring amount of static force that hand can squeeze around dynamometer Carried out twice using their dominant hand Handgrip strength values in the lowest quintile were classified as low muscle strength (cut‐off values : 30 kg for men, 20 kg for women )

26. Chair stand test Cut-off scores of 12 to 16 seconds on the five-repetition sit-to-stand >15 sec for five rises is abnormal Cesari   J Am Geriatr Soc 2009;51:251–9 .

27. 6 Minute walk test Walking speed ≤1 m/s or walking distance <400 m during a 6-min walk Carey et al reported that distance walked over 6 minutes was strongly associated with liver transplant mortality below cutoff of 250 m Morley JE-J Am Med Dir Assoc. 2011 Jul; 12(6)

28. Short Physical Performance Battery Balance tests- Side-by-Side stand Semi-Tandem Stand Tandem Stand Gait speed test- First Gait Speed Test Second Gait Speed Test Chair stand test- Single Chair Stand Test Repeated Chair Stand Test Maximum score=12points score of ≤ 8 points -poor physical performance

29. Stair climb power test- measure of leg power impairment Timed get-up-and-go test- subject to stand up from a chair, walk a short distance, turn around, return and sit down again. TUG time>20 second is abnormal Bischoff Age Ageing 2003; 32 315–20 .

30. Methods to quantify skeletal muscle Test Methods for quantification Single muscle or groups of muscle Anthropometry, DEXA, bioelectrical impedance analysis, impedance plethysmography , ultrasonography , CT or MRI Quality of muscle CT scan attenuation Muscle function Handgrip strength Fiber type Muscle biopsy Contractile function Measurement of maximum strength, maintenance of strength, fatigability

31. Most studies use L3 SMI as test for diagnosis and cuts off used <52.4 cm2/m2 for men and <38.5 cm2/m2

32. Screening of sarcopenia in liver cirrhosis Recommendations Grade of evidence Grade of recommendation Assessment sarcopenia within nutritional assessment II-2 B 1 Assess muscle mass by CT imaging Anthropometry , DEXA or BIA alternatives II-2 B 1 Assess muscle function handgrip strength (HGS) Short Physical Performance Battery (SPPB) II-2 B 1 Assess dietary intake trained personnel dietician II-2 B 1 Clinical Practice Guidelines EASL 2018

33. Clinical Impact of Sarcopenia Effect of sarcopenia on survival in patients with cirrhosis- Study of 248 patients using CT Survival rates of patients with cirrhosis are significantly lower in those with sarcopenia Median survival is 19 ± 6 months in patients with sarcopenia , compared to 34 ± 11 months in patients without sarcopenia Aldo J Montano- Loza - World J Gastroenterol 2014 Jul 7; 20(25): 8061–8071.

34. Sarcopenia adversely impacts in cirrhosis Author(year) N Method to define sarcopenia Outcome Wang(2016) 292 Effect of grip strength, muscle mass, muscle quality, SPPB on transplant wait list mortality Grip strength (HR 0.74), SPPB (HR 0.89), muscle quality (0.77) but not muscle mass (0.91) decreased survival Kalafateli (2016) 232 L3 psoas area and Royal Free Hospital Global Assessment CT measure of psoas muscle area at L3/L4 Post OLT infection (OR 6.55), ventilator requirement (OR 8.5), ICU stay >5 d (OR 7.46) higher in sarcopenic patients Hanai (2016) 149 CT measure of psoas Greater rate of muscle (>3.1%/year) loss increases mortality (HR 2.73) Durand (2014) 376 CT measure of psoas 15 % Increase mortality for each unit decrease in muscle area Masuda (2014) 204 CT measure of psoas Sarcopenia 2 fold increased risk of death, 5.3 fold increased risk of sepsis DiMartini (2013) 338 CT measure of psoas Increased mortality only in men for each unit decrease in skeletal muscle index

35. Survival and sarcopenia Dasarathy et al- Liver Transpl . 2017 May; 23

36. Clinical Impact of Sarcopenia Effect of sarcopenia on survival in patients with cirrhosis and HCC- Observational Study of 116 patients with HCC  SMI was measured by CT Median survival was 16 ± 6 months and 28 ± 3 months, respectively, in patients suffering from concurrent cirrhosis and HCC with or without sarcopenia Meza-Junco J J Clin Gastroenterol 47(10):861–870.

37. Clinical Impact of Sarcopenia Causes of mortality in patients with sarcopenia and cirrhosis 112 patients with cirrhosis observational study Sepsis-related mortality rates in patients with and without sarcopenia patients are 22% and 8%, respectively Risk of infection is higher in elderly patients with sarcopenia than in those without Aldo J Montano- Loza - World J Gastroenterol 2014 Jul 7; 20(25): 8061–8071.

38. Clinical Impact of Sarcopenia Post-transplantation survival Risk of post-transplantation mortality increases as the psoas muscle cross-sectional area decreases (HR = 3.7/1000 mm 2 decrease in psoas area) Sarcopenia is an independent prognostic factor for post-transplant mortality (HR = 2.06, P = 0.047) 10% incremental increase in muscle mass was associated with a 9% shorter length of stay and 12% shorter ICU stay Glen R Morrel et al- J Ren Nutr . 2016 Jul; 26(4): 258–264

39. Clinical Impact of Sarcopenia Other post-transplantation outcomes Study of CT scans of 163 liver transplant recipients Frequency of post-transplantation infection is higher in patients with sarcopenia than in those without (17.7% vs 7.4%, P = 0.03) Infection risk was found to be fourfold higher in patients with lowest quartile of muscle mass compared with highest quartile Aldo J Montano- Loza - World J Gastroenterol 2014 Jul 7; 20(25): 8061–8071.

40. Sarcopenia in Post Transplant Prospective study of 63 transplant patients Median weight gain at 1 and 3 years was 5.1 kg and 9.5 kg, respectively Much of this weight gain is an increase in fat mass Prevalence of sarcopenia , defined by cross sectional imaging, increased from 62.3% pretransplant to 86.8% post-transplant roughly one year after transplant Tsien C, Garber A et al- J Gastroenterol Hepatol . 2014;29:1250–1257

41. Sarcopenia in HCC Metanalysis of 13 studies comprising 3,111 patients Significant association between sarcopenia and all-cause mortality (crude HR = 2.04, 95% CI: 1.74-2.38)  Loss of skeletal muscle mass was associated with tumor recurrence (crude HR = 1.85, 95% CI: 1.44-2.37) Chang K et al, Liver Cancer 2018;7:90–103

42. Sarcopenia in Severe alcoholic hepatitis 81 patients with SAH Sarcopenic group had shorter overall survival time (47.7 vs. 29.3 months, P = 0.072) and 90-day survival (76.7 vs 62.3 days, P = 0.103) than non- sarcopenic group D.S Song et al, Journal of hepatology , April 2015 Page S762

43. Sarcopenia in Cirrhosis Meta analysis of 20 studies -4037 cirrhosis patients- Most of the studies used CT to diagnose sarcopenia 2 studies used bioelectrical impedance analysis (BIA) 10 studies used skeletal muscle index (SMI) 8 studies used total psoas muscle area (TPA) Gaeun Kim et al- Plos one October 24, 2017

44. Results Prevalence of sarcopenia in cirrhosis- 48.1% Men-61 %, Female- 39 % Mortality- 3.23 times higher than non sarcopenic group Higher mortality in Asian participants Increased risk of complications such as infection compared to those without sarcopenia Higher muscle mass – significant reduction in 47% complication occurence Gaeun Kim et al- Plos one October 24, 2017

45. Liver cirrhosis and sarcopenia Tandon et al(2012)- 142 cirrhotic patients with CT scan Overall prevalence of sarcopenia-41% Compared to non sarcopenics , sarcopenic cirrhotic patients had lower survival at 1 yrs : 63% vs 79% 2 yrs : 51% vs 74% 3 yrs: 51% vs 70% Tandon et al- Liver Transpl .  2012 Oct;18(10):1209-16

46. Liver cirrhosis and sarcopenia Montano- Loza et al (2014)- 248 cirrhotic patients with CT scan Overall prevalence of sarcopenia-45% Compared to non sarcopenics , sarcopenic cirrhotic patients had - More infectious complications : 26% vs 15% Longer ICU stay : 12±2 days vs 6 ± 1 day Longer hospital stay : 40 ±4 days vs 25 ±3 days MELD score- 20 ±1 vs 16 ±1 Montano- loza et al- Liver Transpl .  2014 Jun;20(6):640-8.

47. Liver cirrhosis and sarcopenia Hanai et al(2015)- 130 cirrhotic patients with CT scan Overall prevalence of sarcopenia-68% Compared to non sarcopenics , sarcopenic cirrhotic patients had Higher mortality -76% vs 24% Survival at 1 yr : 85% vs 97% Survival at 2 yrs : 63% vs 79% Survival at 3 yrs: 53% vs 79% Hanai et al- Nutrition .  2015 Jan;31(1):193-9

48. MELD Sarcopenia score 585 patients with a median MELD score of 14 (IQR 9-19), of which 254 (43.4%) were identified as having sarcopenia Median waiting list survival was shorter in patients with sarcopenia than those without (p<0.001) MELD- Sarcopenia score : MELD + (10.35 * Sarcopenia ) Discriminative performance of the MELD Sarcopenia score (c-index 0.820) for 3-month mortality was lower than MELD score alone (c-index 0.839) Van Vugt - Journal of Hepatology , 68(4), 707–714.

49. Management

50. Interventions 1.High energy, high protein diet 1.2–1.5 g of protein gm/kg of body weight per day (total 35–40 kcal/kg total energy intake per day Plant proteins have an advantage over animal protein, which are rich in branched-chain amino acid After even overnight fast, patients with cirrhosis shift quickly to fat and protein catabolism, which leads to rapid muscle breakdown Sancak Y et al Science 320(5882):1496–1501

51. 2. Late evening snack Complex carbohydrate snack with protein such as cheese on wholemeal bread Mechanism - Minimises muscle breakdown during overnight fasting in the context of low hepatic glycogen stores Evidence- Metanalysis revealed increased respiratory quotient (increased use of glucose) and nitrogen balance and reduced muscle protein breakdown CD Tsien , AJ McCullough, S Dasarathy J Gastroenterol Hepatol , 2012 Dietary recommendations for patients with CLD should include a “late-evening energy dense snack” 50-100 gm Carbohydrates ~ 20% Calories ~ 13% Proteins Preferably BCAA rich

52. 3. BCAA supplementation Oral granules leucine / isoleucine / valine 7.5 g/ 3.75 g/3.75 g (dissolved in carbonated beverage) 6 compensated alcoholic cirrhotic patients and 8 controls, serial vastus lateralis muscle biopsies were obtained before and 7h after a single oral BCAA mixture enriched with leucine    Increased myostatin expression, impaired mTOR signaling and increased autophagy in cirrhosis compared to controls (p<0.01) Tsien C et al- Hepatology 61(6):2018–2029.

53. Plasma level BCAA correlate S. Albumin Promotes protein synthesis muscles Improve glucose metabolism stimulate mTOR signalling pathways BCAA secretion HGF hepatic stellate cells decreased serum ratio BCAA to AAA Basis BCAA supplementation chronic liver disease BCAA in Liver Disease Japanese Society - Recommend use of BCAA to preserve liver function and inhibit carcinogenesis Kumada et al. Hepatol Res. 2010 ASPEN & ESPEN – use recommended Clinical Nutrition, 2006

54. Effect of BCAA outcome in cirrhosis Author No. Treatment duration Dose(gm) Outcome measure Result comments Horst et al 1984 37 21 20-60 Nitrogen balance - ve 20 g increase to 60, both groups achieved similar nitrogen balance without HE Fiaccadori et al 1988 42 28 25 Nitrogen balance + ve BCAA mixture improved nitrogen balance Marchesni et al 1990 61 90 0.24/kg bw Nitrogen balance + ve Semiquantitative nitrogen balance better with BCAA Guarnieri et al 2011 7 90-120 0.45/kg bw Nitrogen balance + ve BCAA improved nitrogen balance compared to lipid-carbohydrate supplement

55. 4. Exercise 30 min of moderate intensity walking 3– 4 times per week in combination with resistance training such as light hand weights three times per week as tolerated Resistance exercise(RE) can stimulate muscle protein synthesis Endurance exercise (EE) may improve the exercise capacity and muscle strength Hornberger TA- Proc Natl Acad Sci U S A 103(12):4741–4746.

56. Exercise in cirrhosis J Hepatol 2018 Jun 30. S0168-8278(18)32170-6 Improvement in QOL and performance with exercise ± diet supplementation, no significant change in muscle mass

57. 5. Testosterone therapy Intramuscular testosterone decanoate or topical testosterone gel Testosterone gel in 12 hypogonadal patients with cirrhosis increased hand grip strength from 34.03 kg to 39.18 kg(p<0.001) Sinclair M et al J Gastroenterol Hepatol 31(3):661–667

58. 6.Normalisation of portal HTN Insertion of trans-jugular intrahepatic porto -systemic shunt May improve nutrient absorption by reducing gastropathy / enteropathy , and may reduce systemic inflammatory driver of muscle breakdown

59. Evidence to suggest sarcopenia reversal improves survival In a study of TIPSS outcomes, muscle mass improved post-TIPSS in 41 of 57 patients. 12-month mortality of patients with reversal of sarcopenia was 9.8% vs. 43.5% in those in whom sarcopenia persisted (P=0.007) C Tsien - Eur J Gastro Hepatol , 2013

60. Rifaximin 550 mg twice daily- Hypothetically may downregulate myostatin levels by reducing serum ammonia Need larger studies IGF-1 therapy No human studies yet Increases mTOR signalling Reduces myostatin -induced blockage of satellite cell differentiation and proliferation

61. Myostatin inhibitors- First human trials of a myostatin inhibitors named MYO‐029, a recombinant human antibody, began in 2004 Myostatin antibodies, anti‐ myostatin peptibodies , activin A antibodies, soluble (decoy) forms of ActRIIB , anti‐ myostatin adnectin , and ActRⅡB antibodies BYM‐338 showed a dose‐dependent increase in lean body mass compared to placebo (3mg/kg, 10mg/kg vs. placebo) and substantial reductions in body fat in Myositis (p<0.01)

62. Author (Year) Patients Duration Exercise Nutrition Significant Outcome Zenith et al (2014) 21 8 weeks 30+ minutes 3/week Increased peak VO2, increased muscle mass, decreased fatigue Roman et al. (2014) 17 12 weeks 60 minutes 3/week Leucine 10 g/day Increased exercise capacity and leg muscle mass, improved quality of Life Debette-Gratien et al. (2015) 8 liver transplant 12 weeks 60 minutes 2/week Increased VO2, increased muscle strength and 6-minute walk distance Nishida et al. (2017) 6 12 months 140 minutes/ week BCAA 12.45 g/day Increased aerobic capacity as assessed by lactate threshold Berzigotti et al. (2017) 50 16 weeks 60 minutes/week 1000 kcal/day 25% protein Decreased HVPG, decreased BMI, increased VO2, decreased leptin Kitajima et al. (2017) 21 48 weeks BCAA 12 g/day Stable muscle mass and decreased myosteatosis in the 11 patients

63. Nutritional management principles in patients with liver cirrhosis Recommendations Grade of evidence Grade of recommendation Nutritional counselling multidisciplinary team II-2 C 1 35 kcal/kg actual body weight   Daily protein intake 1.5 g/kg actual body weight II-2 B     II-2 B 1 Late evening oral nutritional supplementation (ONS) breakfast containing proteins decompensated cirrhotics II-1 B 1 BCAA supplements decompensated cirrhotic patients II-1 B 1 Clinical Practice Guidelines EASL 2018

64. Nutritional management principles in patients with liver cirrhosis Recommendations Grade of evidence Grade of recommendation Avoid hypomobility Personalized physical activity program decompensated patients III C 1 Nutritional lifestyle program achieve weight loss ( > 5–10%) obese cirrhotic patients (BMI >30 kg/m 2 corrected water retention) II-2 C 1 Moderately hypocaloric (-500–800 kcal/day) diet adequate protein ( > 1.5 g protein/kg BW/day) achieve weight loss obese cirrhotic patients III C 2 Clinical Practice Guidelines EASL 2018

65. Malnutrition in patients undergoing liver transplantation – postop nutrition Recommendations Grade of evidence Grade of recommendation After liver tx normal food/enteral tube feeding within 12–24 hours post-op II-2 B 1 Oral/enteral nutrition not possible prefer parenteral nutrition to no feeding II-2 B 1 After acute postop phase energy intake 35 kcal / kg/ protein 1.5 g / kg / d II-2 C 1 After other surgical procedures, manage patients with chronic liver disease according to the ERAS protocol III C 1 Utilize enteral tube feeding/ PN energy intake (25 kcal / kg/d) protein intake (2.0 g / kg/d) in obese patients III C 1 Clinical Practice Guidelines EASL 2018

66. Micronutrients Recommendations Grade of evidence Grade of recommendation Cirrhotics administer micronutrients vitamins confirmed/clinically suspected deficiency III C 1 Assess vitamin D levels cirrhotics patients highly prevalent adversely affects clinical outcomes II-3 B 1 Supplement vitamin D orally vitamin D levels <20 ng/ml reach serum vitamin D (25(OH)D) >30 ng/ml III B 1 Cirrhotics with ascites sodium restriction improve diet palatability II-2 B 1 Clinical Practice Guidelines EASL 2018

67. Sarcopenic obesity Low muscle mass- either low muscular strength or low physical performance Accompanied by a high fat mass

68. Sarcopenic Obesity Sarcopenic obesity is a confluence of 2 major comorbidities , carrying with it higher rates of mortality and morbidity Sarcopenic obesity has been reported in patients with NAFLD and after liver transplantation Combination of skeletal muscle loss and increased fat may contribute to development of metabolic components including insulin resistance, diabetes mellitus, hyperlipidemia and possibly NAFLD

69. NAFLD and Sarcopenia Korean Sarcopenic Obesity Study (KSOS) 452 apparently healthy adults enrolled in ongoing prospective observational Korean cohort study SMI(marker of sarcopenia ) and LAI(liver attenuation index- NAFLD) positive relationships with HDL-cholesterol negative relationship with triglyceride, ALT and total body fat Hong HC Hepatology 2014 May;59(5):1772-8.

70. 678 patients cirrhosis analysed by CT scan Sarcopenia 292 (43%) 135 sarcopenic obesity (20%) 353 myosteatosis (52%) Cirrhotic patients with sarcopenic obesity had worse median survival (22 ± 3 months, P < .001) compared to those with normal body composition (median survival -95 ± 22 months)

71. Summary Sarcopenia in liver diseases has adverse outcome Better understanding of pathogenesis has helped plan molecular therapies to treat sarcopenia Tools to identify sarcopenia in liver diseases help identify the patients at risk Most effective treatment strategy -both diet-induced weight loss and a regular multi-component exercise program

72. Take Home Messages Look for sarcopenia in all liver disease patients Treat sarcopenia to improve survival in pre transplant as well as post transplant patients Sarcopenic obesity has higher mortality and morbidity than sarcopenia or obesity itself Diet and regular multi-component exercise program are integral part in management

73. Food for thought Can sarcopenia be reversed in cirrhosis ? Can treating sarcopenia reverse cirrhosis? Has time come for Sarcopenia -MELD score?

74. Thank you