Role of Nutritional Support in the Treatment of Alcoholic Liver Disease

Transcription

1 Riunione Monotematica AISF Alcoholic Liver Disease: The New Challenge Roma, 4-6 Ottobre 2017 Role of Nutritional Support in the Treatment of Alcoholic Liver Disease Esmeralda Capristo Divisione di Patologie dell Obesità Fondazione Policlinico Gemelli Roma

2 La sottoscritta dichiara di non aver avuto/di aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione non contiene/contiene discussione di farmaci in studio o ad uso off-label

3 Malnutrition is the most frequent complication in alcoholic liver disease (ALD) and adversely affects the clinical outcomes of the disease Loss of skeletal muscle mass = SARCOPENIA Perturbations in Energy Metabolism Kim MS, et al. W J Gastroenterol 2016; Dasarathy J, et al. Alcohol Clin Exp Res 2017

4 Cumulative survival in cirrhotic patients with different degree of malnutrition N: 1053 Modified from Merli M, et al. Hepatology 1996

5 Hepatology 2010

6 Factors contributing to sarcopenia in alcoholic liver disease Reduced oral intake due to inebriated state Anorexia Dysgeusia Low quality of diet Hypermetabolism Low sodium diet Acute hepatitis- cytokines Hyperammonemia of liver disease Other complications that affect nutrient intake (gastrointestinal bleeding, encephalopathy) Diarrhea, portal hypertensive enteropathy with reduced nutrient absorption Nausea, Vomiting Kim MS, et al. W J Gastroenterol 2016; Dasrathy J, et al. Alcohol Clin Exp Res 2017

7 Factors specific to alcohol induced sarcopenia Direct metabolism of ethanol by muscle with changes in redox ratio Ethanol induced skeletal muscle mitochondrial dysfunction Protein adducts with increased muscle autophagy Impaired muscle protein synthesis Dasarathy S, et al. Clin Liver Dis 2016; Dasarathy J, et al. Alcohol Clin Exp Res 2017

8 Pathophysiological perturbations and potential therapeutic targets to reverse sarcopenia in alcoholic liver disease Kim MS, et al. W J Gastroenterol 2016

9 Body composition in ALD kg 80 CONTROLS ALCOHOLICS * 0 Weight FFM FM * P < 0.05 Addolorato G, Capristo E, et al Alcohol Clin Exp Res 1997

10 Body composition in ALD

11 CONTROL ALD CHILD A ALD CHILD B ALD CHILD C Red colour indicates muscle, green-subcutaneous fat and blue-visceral fat.

12 Sarcopenic obesity = decreased skeletal muscle mass and increased visceral adiposity Hara N, et al. Intern Med 2016

13 Energy metabolism in Liver Cirrhosis Correlation between measured and predicted resting energy expenditure (REE) in 473 patients [, men (n = 253);, women (n = 220)] with biopsy-proven liver cirrhosis (r = 0.70, P < for all patients; r = 0.619, P < for men; r = 0.518, P < for women). Manfred J Müller et al. Am J Clin Nutr 1999;69:

14 1998;27:

15 Energy expenditure, substrate oxidation, and body composition in subjects with chronic alcoholism Addolorato G, Capristo E, et al Alcohol Clin Exp Res 1997

16

17 Factors affecting severity/measures of malnutrition in ALD Duration of alcohol use/abuse Amount of alcohol consumed Time of measurement from last alcohol consumed Other underlying causes of liver disease Severity of liver disease (Child-Pugh/MELD score) Specific measure used (anthropometry, body composition, circulating proteins, immune function, muscle mass, indirect calorimetry) Dasarathy S, et al. Clin Liver Dis 2016

18 A proposed algorithm for nutritional screening and assessment in patients with cirrhosis modified from Tandon P, et al. Hepatology 2017

19 Complex relationship between malnutrition, cirrhosis-related complications, transplantation, and survival Tandon P, et al. Hepatology 2016

20 Nutrition Support in ALD Preventing alcohol- induced Providing adequate daily malnutrition requirements Reducing Hypermetabolism Slow the disease progression Reduce complications Delay liver transplantation Decrease mortality rate Ghorbani Z, et al. Hepatobiliary Pancreat Dis Int 2016; Desarathy S, et al. Clin Liv Dis 2016

21 Nutritional Therapies in ALD and cirrhosis According to the Guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN): Daily requirements of protein: Daily energy requirements : gr/kg/day kcal/kg/day Starvation or long-term fasting should be avoided and intake of frequent meals is necessary to prevent alcohol induced hypoglycaemia; Enteral Nutrition Support is recommended in patients with inadequate oral nutrition intake; Parenteral Nutrition is recommended when fasting last longer than 72 h; Protein restriction even in cirrhotic patients is not recommended because it can result in muscle wasting, exacerbations of hepatic encephalopathy and hyperammonemia ESPEN Guidelines on Parenteral Nutriton in Hepatology, Clin Nutr 2009; ESPEN Guidelines on Enteral Nutriton in Hepatology; Clin Nutr 2006.

22 Nutritional treatment in alcoholic liver disease Step 1. Abstinence from alcohol Step 2. Nutritional support: increased protein/calorie intake Oral supplementation Enteral nutrition Parenteral nutrition Amino acid supplementation Micronutrient replacement Step 3. Increase physical activity Step 4. Novel targets Myostatin antagonists mtorc1 activators Muscle targeted antioxidants Autophagy regulators Mitoprotective agents Cell permeable TCA cycle intermediates Specific amino acid and analog supplementation Dasarathy S, et al. Clin Liver Dis 2016

23 modified from Tsien C, et al. Hepatology 2015;61: Metabolic and Molecular Response to Leucin-Enriched Branched Chain Amino Acid Supplementation in the Skeletal Muscle of Alcoholic Cirrhosis N= 6 Cirrhotics N= 8 Controls Acute oral load of 14 gr BCAA (7.5 gr leucine)

24 Vitamins: Dietary Supplementation in ALD - Vitamin A and carotenoids - Vitamin C - Vitamin E - Vitamin D - Vitamin B1, B3, B12 Antioxidant and anti-inflammatory agents: - Silymarin - Curcumin - Resveratrol - Citrus flavonoids - Tea polyphenols - Probiotics - Zinc, Selenio - S-adenosylmethionine (SAM) - Garlic - Soy protein Kumar A, et al. Hepatology 2017; Ghorbani Z, et al. Hepatobiliary Pancreat Dis Int 2016; Desarathy S, et al. Clin Liv Dis 2016

25 Emerging Nutritional Therapies Targeting skeletal muscle mithocondrial dysfunction and generation of reactive oxygen species Myostatin antagonists Long-term ammonia lowering therapy Autophagia regulators Cohen S, et al. J Cachexia Sarcopenia Muscle 2015; Qi X, et al. J Cell Sci 2013; Kumar A, et al. Hepatology 2017

26 Hagström H, et al. J Hepatol 2016;65:363-8.

27 Body mass index and risk of severe liver disease Severe liver disease Hagström H, et al. Gut 2017

28 Hagström H, et al. Gut 2017

29 Liver disease and candidacy for bariatric surgery

30

31 Conclusions: Malnutrition Among the different etiologies of liver disease, malnutrition and sarcopenia are believed to be most severe in ALD Sarcopenia adversely affects clinical outcomes including survival, quality of life, other complications of liver disease ans post-liver transplant outcomes Direct effetcs of ethanol and its metabolites, as well as the consequences of cirrhosis, including hyperammonemia, contribute to the pathogenesis of sarcopenia Anabolic resistance in alcoholic cirrhosis is mediated by impaired mtorc1 signaling Therapeutic goals include an improvement in skeletal muscle mass as well as contractile function Kumar A, et al. Hepatology 2017; Desarathy J, et al. Alcohol Clin Exp Res 2017

32 Conclusions: Nutrition Late evening snacks, breakfast and frequent meals have the potential to reduce the development and progression of sarcopenia Dietary supplements have shown beneficial effects in animals model of ALD and might be useful in clinical practice Weight loss in overweight and obese ALD patients is warranted to improve disease outcome and reduce complication Prevention and early detection of alteration of nutritional status in all stages of ALD Kumar A, et al. Hepatology 2017; Ghorbani Z, et al. Hepatobiliary Pancreat Dis Int 2016; Desarathy S, et al. Clin Liv Dis 2016

33 Thanks