(Mal)nutrition and liverdisease

Transcription

1 (Mal)nutrition and liverdisease Giulio Marchesini Alma Mater Università di Bologna SSD Malattie del Metabolismo e Dietetica Clinica

2 Disclosures Giulio Marchesini Advisory Board: Eli Lilly, Gilead Honoraria: Sanofi, Merck Sharp & Dome, Novartis Clinical Studies: Eli Lilly, Sanofi, Novo Nordisk, GILEAD, GENFIT, Jannsen, Glaxo

3 Sommario (Mal)nutrizione delle malattie epatiche Metodi di valutazione Passato, presente e futuro Stato nutrizionale e outcomeclinico Cirrosi Trapianto di fegato Trattamento Diete speciali/perdita di peso

4 Anand, JClinExpHepatol2017 Malnutrition in cirrhosis

5 Protein-Calorie Malnutrition Percent ideal weight (%) Diagnostic Parameters Triceps Skinfold Thickness ( 12.5 mm) Mid-Arm Muscle Circumference (MAMC 25.3 cm) Creatinine-Height Index (%) Albumin ( 35 g/liter) Transferrin ( 180 mg/dl) Total Lymphocyte Count ( 1500 cells/mm 3 ) Delayed Cutaneous Hypersensitivity to a Battery of Skin Tests (DNCB or others) Mendenhall, Am J Clin Nutr 1986

6 Metodi più accessibili Antropometria Bioimpedenzometria

7 Nutritional Status in Cirrhosis by Etiology Alcohol-related N = MAMA < 5th percentile MAFA < 5th percentile Males Females Virus-B-related Males Females Cryptogenic Males Females Italian Multicenter Cooperative Project J Hepatol 1994

8 Nutritional Status in Cirrhosis All Cases Severe Malnutrition Moderate Malnutrition No Malnutrition Over Nutrition Males Females C-P Class A - Males A - Females B - Males B - Females C - Males C - Females Italian Multicenter Cooperative Project J Hepatol 1994

9 Merli, Hepatology pts with cirrhosis, 5-yr f-up, 419 events

10 MUST Calculator (Malnutrition Universal Screening Tool)

11 Recommended cut-points for weakness and low muscle mass for men and women Cut-point Men Women Grip strength adjusted for BMI (GS BMI ) < 1.00 < 0.56 Appendicular lean body mass adjusted for BMI (ALM BMI ) Skeletal muscle index adjusted for weight (SMI weight ) < < < 29.0 < 22.9 GS BMI and ALM BMI cutpoints were identified by the NHI Sarcopenia Project. SMI weight cutpoints have been defined by BIA as SMI values below 2 standard deviation of a normal healthy population, where SMI% = total appendicular skeletal muscle mass (kg) / body weight (kg) 100.

12 Combined nutritional assessment in ptson the waiting list for OLT Ribeiro, Nutrition 2018

13 Mazurak, LiverTransplant2017 CT-assessed myosteatosis

14 Koo, J Hepatol 2017 Sarcopeniaand NAFLD severity

15 Sarcopeniaand NAFLD severity Multivariate model 1 was adjusted for age, gender, BMI, smoking, hypertension, and diabetes. Multivariate model 2 was adjusted for lipid profile and ALT + factors included in model 1. Multivariate model 3 was adjusted for hscrp +factors included in model 2. Multivariate model 4 was adjusted for HOMA-IR + factors included in model 2. Koo, J Hepatol 2017

16 Sarcopenia& fibrosis in NAFLD (KNHANES cohort: 2761/9676 subjects) Sarcopenia index (SI) calculated as: SI = total ASM (kg)/bmi (kg/m 2 ). Sarcopenia defined as SI <0.789 in men and <0.521 in women. NFS, Fib-4 & Forns Lee, Hepatology 2016

17 225 consecutive patients with histological diagnosis of NAFLD. Skeletal muscle index (SMI %) assessed by BIA. Sarcopeniadefined as SMI 37 in males and 28 in females. Petta, Alim Pharmacol Ther 2017

18 Sommario (Mal)nutrizione delle malattie epatiche Passato, presente e futuro Metodi di valutazione Stato nutrizionale e outcomeclinico Cirrosi Trapianto di fegato Trattamento Diete speciali/perdita di peso

19 Obesity- and sarcopenia-associated risks Atkins et al, J Am Geriatr Soc 2014

20 Clinical decompensation (%) 161 patients with compensated cirrhosis, followed until CD (ascites, hepatic encephalopathy, or variceal hemorrhage), or until September 2002 (median follow-up, 59 months) Etiology of cirrhosis: Viral, 68%; Alcohol, 22%; Crypto, 5%; Others, 5% Berzigotti, Hepatology 2017

21 Sarcopenia& survival in cirrhosis and HCC Cirrhosis HCC Montano-Loza, World J Gstroenterol 2014

22 Sarcopeniaand survival in the waiting list for OLT 396 pts newly listed for OLT in 2012 Carey, Liver Transplantation 2017

23 Adults with cirrhosis evaluated for OLT in the perid , University of Alberta, Edmonton, Canada Montano-Loza, J Cachexia, Sarcopenia & Muscle 2016

24 669 cirrhotic patients consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopeniawas defined using previously published gender and body mass index specific cutoffs. Sarcopeniawas present in 298 patients (45%). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD and the L3 SMI were associated with mortality. Modification of MELD to include sarcopeniais associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. Montano-Loza, Clin Transl Gastroenterol 2015

25 VATI & HCC-free survival in cirrhosis Patients with cirrhosis (n = 678; 457 male) who were assessed for LT (289 with HCC) were evaluated for body composition analysis. Patients who underwent LT (n = 247, 168 male) were subsequently evaluated for body composition, and 96 of these patients (78 male) had HCC. Montano-Loza, Hepatology 2018

26 VATI & HCC-free survival in cirrhosis In male patients with HCC who underwent LT, a VATI 65 cm 2 /m 2 adjusted for Milan criteria was independently associated with higher risk of HCC recurrence (HR, 5.34; 95% CI, ; P=0.03). Montano-Loza, Hepatology 2018

27 Survival (%) Both sarcopeniaand myosteatosiscause an excess of death rate for sepsis Montano-Loza, J Cachexia, Sarcopenia & Muscle 2016

28 Sommario (Mal)nutrizione delle malattie epatiche Passato, presente e futuro Metodi di valutazione Stato nutrizionale e outcomeclinico Cirrosi Trapianto di fegato Trattamento Diete speciali/perdita di peso

29 BCAA Italian Study Group -Results Cumulative Event-free Rates Months BCAA M-DXT; P = L-ALB; P = Marchesini, Gastroenterology 2003

30 Meta-analysis on the effect of enteral BCAA vs. PL or control diets for hepatic encephalopathyin randomized controlled trials. *risk difference (RD) with 95% confidence interval (CI) Hayashi 1991 Horst 1984 Marchesini 1990 Marchesini 2003 Muto 2005 Plauth 1993 Les 2011 Overall NOTE: Weights are from random effects analysis RD (95% CI) 0.34 (0.15, 0.52) 0.24 (0.01, 0.48) 0.45 (0.23, 0.66) 0.09 (-0.11, 0.28) 0.05 (-0.29, 0.38) -0.01(-0.24, 0.22) 0.28 (-0.01, 0.56) 0.21 (0.09, 0.34) Weight Gluud, JNutr2013

31 Meta-analysis on the effect of enteral BCAA vs.pl or control diets for mortality in trials on patients with HE *risk difference (RD) with 95% confidence interval (CI) Horst 1984 Marchesini 1990 Marchesini 2003 Muto 2005 Plauth 1993 Egberts Les 2011 Overall NOTE: Weights are from random effects analysis RD (95% CI) 0.06 (-0.08, 0.20) -0.06(-0.15, 0.04) 0.04 (-0.10, 0.18) -0.19(-0.48, 0.11) 0.00 (-0.15, 0.15) 0.00 (-0.16, 0.16) 0.01 (-0.27, 0.28) -0.01(-0.07, 0.04) Weight Gluud, JNutr2013

32 Optimizing nutritional support in the setting of cirrhosis Perumpail, Nutrients 2017

33 Conceptual framework of the relation between nutritional status and physical fitness in ESLD Duarte-Rojo, Liver Transplantion 2018 Physical deconditioning, determined by a low CPE (cardiopulmonary endurance), and sarcopenia, a surrogate for progressive malnutrition, are cofactors leading to functional deterioration. As physical deconditioning progresses, patients exercise less and use less energy as part of NEAT. Frailty is conceptualized as the extreme of functional deterioration, leading to clinical outcomes.

34 Raccomandazioni per l apporto di proteine e esercizio fisico (adulti > 65 anni) Recommendations For healthy older adults, we recommend a diet that includes at least 1.0 to 1.2 g protein/kg body weight/day. For certain older adults who have acute or chronic illnesses, 1.2 to 1.5 g protein/kg body weight/day Consider may be indicated, with even higher intake for individuals renal with severe illness or injury. function! We recommend daily physical activity for all older adults, as long as activity is possible. We also suggest resistance training, when possible, as part of an overall fitness regimen. Deutz NEP et al., Clin Nutr 2014

35 Lifestyle intervention in cirrhosis: The SportDiet Study A prospective, uncontrolled pilot study in 60 patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient [HVPG] 6 mm Hg), and body mass index (BMI) 26 kg/m 2. All were enrolled in an intensive 16-week LS intervention program (personalized hypo-caloric normoproteic diet and 60 min/wk of supervised PA). Changes in HVPG and BW were predefined as clinically relevant if 10% and 5%, respectively. Reassessment after 6 moin 50 cases. Etiology of cirrhosis: Viral, 18; Alcohol; 19, NAFLD, 12; Autoimmune, 1 Berzigotti, Hepatology 2017

36 Exercise model for patients with ESLD Duarte-Rojo,, Liver Transplantion 2018