Liver Disease A brief overview of liver disease

Liver Disease A brief overview of liver disease and review of current nutrition recommendations Michael Tan Sodexo Dietetic Intern April 7 th, 2016

Liver Trivia • How many functions does the liver have? • • 100 250 500 750 • What percentage of liver cells must be lost before physiological function is impaired? • • 20 -30% 40 -50% 60 -70% 80 -90% Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015. Cirrhosis and chronic liver failure: part I diagnosis and evaluation. American Family Physician. http: //www. aafp. org/afp/2006/0901/p 756. html. Accessed March 21 st, 2016.

Anatomy of the Liver • Four anatomical lobes • Right lobe (largest) • Receives blood from right hepatic artery • Quadrate lobe • Caudate lobe • Left lobe • Receives blood from left hepatic artery • Functional unit = lobule • Lobules constructed around a central vein • Lobule composed of cellular plates and bile canaliculi • Bile canaliculi collects bile and carries it to bile duct Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Functions of the Liver • Over 500 functions • Carbohydrate metabolism • Glycogenesis, gluconeogenesis • Lipid metabolism • Lipogenesis, lipolysis • Protein metabolism • Synthesis of serum proteins, prothrombin • Enzyme metabolism • Synthesis of alkaline phosphatase, AST, ALT Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Functions of the Liver • Vitamin metabolism • Dephosphorylation of thiamine • Bile acid metabolism • Heme metabolism • Storage • Glycogen, fats, fatty acids, fat-soluble vitamins • Other (i. e. detoxification) Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Pertinent Lab Values Test Clinical Implications Blood Ammonia Increased in cirrhosis, liver failure; does not always correlate to hepatic encephalopathy Albumin Decreased in liver disease and inflammatory states Total Protein Decreased in liver disease and inflammatory states Urine bilirubin Indicates biliary obstruction or red blood cell hemolysis Alkaline phosphatase Increased in liver disease, malignancy, biliary duct obstruction, and bone diseases AST May indicate liver disease; also elevated in cardiac and muscle damage ALT Detects hepatocellular injury Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Pathophysiology common to the Hepatobiliary Tract • Jaundice • Yellowish tint to body tissues as a result of elevated extracellular levels of bilirubin • Portal Hypertension • High blood pressure in hepatic portal vein which can cause ascites • Encephalopathy • Impaired mental status as a result of liver disease

Liver Disease Overview • Hepatitis • Inflammation of the liver caused by virus, bacteria, toxins, obstruction, parasites, or chemicals • Viral Hepatitis (A, B, C, D, E) • Alcoholic Liver Disease (ALD) • Fatty Liver • Non-alcoholic steatohepatitis (NASH) • Cirrhosis • Late stage of liver disease characterized by scar tissue impairing blood flow through liver • Commonly caused by Hepatitis C or alcoholism Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Disease - Hepatitis • Hepatitis A • Transmitted via oral fecal route • Hepatitis B • Transmitted via blood or blood-derived fluids • Hepatitis C • Transmitted via blood or bodily fluids from infected person • Most common reason for liver transplant • Cannot be prevented by vaccination • Can develop cirrhosis • Increased risk of developing liver cancer Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Disease - Hepatitis • Fulminant Hepatitis • Acute liver failure • Rare, but potentially fatal • Sudden loss of liver function with no prior history of liver disease • Secondary to virus, toxin, metabolic disorder, or immunemediated attack • Transplantation is thought to be the only effective treatment Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Disease - Hepatitis • Nutrition Therapy for viral hepatitis • • • Avoidance of alcohol Adequate fluids Good nutrition Small, frequent meals Food restrictions not required Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Disease – Alcoholic Liver Disease • Fatty Liver (steatosis) • Occurs in 90% of chronic alcohol users • May develop in absence of alcohol abuse (nonalcoholic steatohepatitis (NASH)) • Alcoholic Hepatitis • Clinical presentation may include: jaundice, hepatomegaly, ascites, portal hypertensive bleeding, hepatic encephalopathy Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Disease – Alcoholic Liver Disease • Nutrition Therapy for Alcoholic Liver Disease • Oral/enteral supplements for those at risk of undernutrition • Small, frequent feedings • Kcal: 30 -35 kcal/kg • Protein: 1. 5 -2. 0 g/kg • High carbohydrate: 6 -8 g/kg • Vitamin/mineral supplementation • • • Multivitamin with minerals Thiamin (50 -100 mg for 1 -2 weeks) Folic Acid (1 mg per day) Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Alcohol Metabolism • Alcohol ingestion leads to increased fatty acids and can lead to fatty liver disease • Pathway 1: Alcohol dehydrogenase (ADH) • ADH catalyzes ethanol to acetaldehyde • Acetaldehyde converted to acetate • Pathway 2: Microsomal ethanol oxidizing system (MEOS) • Used in chronic alcoholism • Pathway uses energy, as opposed to creating it • Pathway 3: Catalase in peroxisomes • Metabolizes < 10% of ethanol Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Alcohol’s Effect on Vitamins and Minerals • Folic Acid • Most frequent nutritional deficiency in alcoholics • Alcohol interferes with the absorption of folate • Increased requirements in alcoholism • Thiamine • Alcoholism is the most common cause of thiamine deficiency • Can lead to beri and Wernicke-Korsakoff • B 6 • Low levels in > 50% of alcoholics • Also affects Niacin, Vitamin C, Vitamin D, Vitamin K, Vitamin A, Zinc, Iron, Calcium, Potassium, and Magnesium Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015. Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol. 2012; 10(2): 117 -125.

Cirrhosis – Nutrition Therapy • Kcal needs: 35 -40 kcal/kg • Protein needs: up to 1. 6 g/kg • Protein should not be restricted, even for encephalopathy • Patients with cirrhosis frequently malnourished • Restricting protein leads to catabolism of lean body mass and will contribute to NH 4 levels • Fat restriction (< 30% of total kcal) Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Cirrhosis – Nutrition Therapy • Sodium restriction for ascites (2 g per day) • Possible fluid restriction as well • Enteral nutrition often required to prevent further malnutrition • When patient with inadequate oral intake • Diabetes is common in cirrhosis • Consistent carbohydrate intake • Multivitamin use when not contraindicated • Soft diet for esophageal varices Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Cystic Fibrosis (CF) and Liver Disease • Liver Disease is common in those with CF • Most are asymptomatic • Jaundice, ascites, and encephalopathy are rare • Most common complication is portal hypertension • Variceal bleeding occurs in 33% of CF patients with cirrhosis • Evidence supports the use of ursodeoxycholic acid (UDCA) for functional improvement and to prevent overt liver disease Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Transplant – Nutrition Therapy • Pre-transplant • Minimize malnutrition and complications (i. e. ascites) • Can improve post-operative complications • Undernourished patients have higher post-op mortality Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

Liver Transplant – Nutrition Therapy • Post-transplant • Immunosuppressant medication effects • Can cause colitis, high cholesterol, high triglycerides, hyperglycemia, diarrhea, esophagitis • More susceptible to food-borne illnesses • Meet needs of healing • Oral or enteral nutrition should be initiated within 12 -24 hours • 35 -40 kcal/kg and 1. 2 -1. 5 g protein/kg • Manage hyperglycemia • Fluid restriction for ascites • Calcium supplements and multivitamin for bone health Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Malnutrition • Seen in 50 -90% of patients with cirrhosis • More common in patients with alcoholic liver disease (when compared to nonalcoholic liver disease patients) • Common causes • Inadequate oral intake • Metabolic disturbances • Malabsorption • Decreased capacity of the liver and to management store nutrients Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29. Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol. 2012; 10(2): 117 -125.

Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Nutrition Assessment • Should provide assessment of both nutrition status and severity of underlying illness • Intake • Body composition • Protein depletion • Fluid retention • Muscle wasting • Anthropometrics: BMI, mid-arm circumference, bioelectric impedance analysis Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29. Mueller CM. The American Society for Parenteral and Enteral Nutrition (A. S. P. E. N) Adult Nutrition Support Core Curriculum. 2 nd Ed. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition; 2012. Fernandes SA, Bassani L, Nunes FF, Ayodos ME, Alves AV, Marroni CA. Nutritional assessment in patients with cirrhosis. Arq Gastroenterol. 2012; 49(1): 19 -27).

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Nutrition Assessment • Biochemical • Prealbumin, serum albumin, and transferrin correlate to illness severity, but not nutrition status • Micronutrients • Deficiencies in fat-soluble vitamins (A, D, E, K) and zinc are common in liver disease Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Energy recommendations • Based on dry weight • Ideal weight is used when ascites is present • 25 -40 kcal/kg • Compensated, stable: 25 -35 kcal/kg • Malnourished: 30 -40 kcal/kg • REE x 1. 2 -1. 4 can also be used (~30 -35 kcal/kg) Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Energy recommendations • Critically Ill patients • • Malnourished & refeeding risk: 15 -20 kcal/kg ICU stable: 25 -30 kcal/kg Obese: Mifflin St. -Jeor Catabolic: 35 -50 kcal/kg Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Protein recommendations • Historically, protein restriction was recommended • Prevent an increase in ammonia level • Reduce risk of hepatic encephalopathy • However, recent studies show high protein is more beneficial in cirrhosis • Better prognosis • Improvement in overall nutrition status without encephalopathy exacerbation • Protein restriction worsens hepatic encephalopathy • Increases protein catabolism/muscle breakdown Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Protein recommendations • No encephalopathy • 1. 0 -1. 5 g/kg • Prevents muscle catabolism and promotes gluconeogenesis • Acute encephalopathy • Temporary protein restriction (0. 6 -0. 8 g/kg) may be appropriate until cause is determined • Then resume high protein Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Protein recommendations • Critically Ill patients • Malnourished & refeeding risk: 1. 2 g protein /kg • ICU stable: 1. 5 g protein/kg • Obese: 1. 5 -2. 0 g protein/kg ideal body weight Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Carbohydrate recommendations • Many cirrhosis patients have glucose intolerance or diabetes • Glucose should remain < 5 -6 g/kg/d • Fat recommendations • Avoid overfeeding – excess calories can contribute to fat accumulation in liver • Fluid recommendations • Highly individualized • Fluid restriction of 1. 5 L or less may be indicated in the presence of both ascites AND hyponatremia (<120 -125 m. Eq/L) Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Nutrition challenges • Optimizing intake • Protein Supplementation & Hepatic Encephalopathy • It is discouraged to use serum ammonia levels as an indicator to initiate protein restriction • Lack of correlation between ammonia and encephalopathy • Benefits of branched chain amino acids (BCAA) • Increases serum albumin & energy metabolism • Improves quality of life & prevents muscle catabolism • Prebiotics and probiotics may offer benefits Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Nutrition challenges • Nutrition Support • PEG not indicated with ascites • Aspiration risk when feeding to stomach due to gastroparesis (recommend nasoenteral tube) • Concentrated formulas should be considered (fluid balance, ascites, hyponatremia) Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Nutrition challenges • Fluid imbalance, ascites, hepatorenal syndrome • Sodium imbalances common due to fluid abnormalities • Increased fluid intake can exacerbate hyponatremia • Ascites associated with poor nutritional status • Evening snack + post-paracentesis parenteral nutrition reduces mortality in those with refractory ascites • Renal failure complications Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29. Sigal SH. Hyponatremia in cirrhosis. J Hosp Med. 2012; 7(suppl 4): S 14 -S 17 Sorrentino P, Castaldo G, Tarantino L, et al. Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis. J Gastroenterol Hepatol. 2012; 27(4): 813 -822.

ASPEN: Nutrition Assessment and Management in Advanced Liver Disease • Nutrition challenges • Obesity • Obese patients with non-alcoholic fatty liver diseaserelated decompensated cirrhosis benefit from weight loss • Protein needs must still be met • Diabetes and insulin resistance • High rate of insulin resistance in chronic liver disease Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

Review of Nutrition Recommendations Holy Family Hospital A. S. P. E. N. * Hepatitis with encephalopathy Kcal: 30 -35 kcal/kg Protein: 0. 8 g/kg Kcal: REE x 1. 2 -1. 4 Protein: 0. 6 -0. 8 g/kg (temporary during acute encephalopathy) Hepatitis without encephalopathy Kcal: 25 -35 kcal/kg Protein: 1. 0 -1. 2 g/kg Kcal: REE x 1. 2 -1. 4 Protein: 1. 0 -1. 5 g/kg Cirrhosis Kcal: 25 -30 kcal/kg Protein: 0. 8 -1. 2 g/kg Kcal: REE x 1. 2 -1. 4 Protein: 1. 0 -1. 5 g/kg E. S. P. E. N* Kcal: 35 -40 kcal/kg Protein: 1. 0 -1. 5 g/kg *A. S. P. E. N and E. S. P. E. N. : Energy requirement based on dry weight or ideal body weight if ascites present Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

Summary of Nutrition Management of Liver Disease • Increased nutrient needs due to high rate of malnutrition • High protein • Fluid balance is highly individualized • Sodium restriction if ascites present • High rate of diabetes, glucose intolerance • Overfeeding can contribute to fatty liver • Enteral nutrition indicated if needs cannot be met by oral diet • Nasoenteric tube • Standard energy-dense formula Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29.

References 1. Nelms M, Sucher K, Lacey K, Roth S. Nutrition Therapy & Pathophysiology. 3 rd ed. Boston, MA: Cengage Learning; 2015. 2. Cirrhosis and chronic liver failure: part I diagnosis and evaluation. American Family Physician. http: //www. aafp. org/afp/2006/0901/p 756. html. Accessed March 21 st, 2016. 3. Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol. 2012; 10(2): 117 -125. 4. Johnson TM, Overgard EB, Cohen AE, Di. Baise JK. Nutrition assessment and management in advanced liver disease. Nutr Clin Pract. 2013 Feb(1): 15 -29. 5. Mueller CM. The American Society for Parenteral and Enteral Nutrition (A. S. P. E. N) Adult Nutrition Support Core Curriculum. 2 nd Ed. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition; 2012. 6. Fernandes SA, Bassani L, Nunes FF, Ayodos ME, Alves AV, Marroni CA. Nutritional assessment in patients with cirrhosis. Arq Gastroenterol. 2012; 49(1): 19 -27). 7. Sigal SH. Hyponatremia in cirrhosis. J Hosp Med. 2012; 7(suppl 4): S 14 -S 17 8. Sorrentino P, Castaldo G, Tarantino L, et al. Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis. J Gastroenterol Hepatol. 2012; 27(4): 813 -822.

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