Medical Nutrition Therapy for Liver, Biliary System, and Exocrine Pancreas Disorders

1. Medical Nutrition Therapy for Liver, Biliary System, and Exocrine Pancreas Disorders

2. Relationship of Organs of the Upper Abdomen A, Liver (retracted upward); B, gallbladder; C, esophageal opening of the stomach; D, stomach (shown in dotted outline); E, common bile duct; F, duodenum; G, pancreas and pancreatic duct; H, spleen; I, kidneys. Courtesy The Cleveland Clinic Foundation, Cleveland, Ohio, 2002.

3. The Liver • Largest gland in the body (about 1500 g) • Essential for life, though survival is possible with 10-20% function • Plays major role in macronutrient and micronutrient digestion, metabolism, and storage • Metabolizes steroids, detoxifies drugs, alcohol, ammonia

4. Diseases of the Liver • Acute viral hepatitis • Fulminant hepatitis • Chronic hepatitis • Alcoholic liver disease, alcoholic hepatitis, and cirrhosis • Non-alcoholic hepatic steatosis (NASH)

5. Diseases of the Liver • Cholestatic liver diseases —Primary biliary cirrhosis —Sclerosing cholangitis • Inherited disorders • Other liver diseases

6. Acute Viral Hepatitis • Widespread inflammation of the liver that is caused by hepatitis viruses A, B, C, D and E • Hep A: oral-fecal route • Hep B and C: body fluids • Hep D: occurs only in pts with Hep B • Hep E: oral-fecal route; seen more often in Asia, Africa, Mexico Hasse JM et al. ASPEN Nutrition Support Practice Manual, 2nd edition, 2005

7. Acute Viral Hepatitis • Four phases of symptoms: 1. Prodromal phase 2. Preicteric phase 3. Icteric phase 4. Convalescent phase

8. Risk Factors for Chronic Viral Hepatitis • Injection drug use • Chronic hemodialysis • Blood transfusion or transplantation prior to 1992 (HCV) • Receipt of blood (including needlestick) from a donor subsequently testing positive for HCV

9. Risk Factors for Chronic Viral Hepatitis • Receipt of clotting factor concentrates produced before 1987 • Asian ancestry (HBV) • Unvaccinated health care workers • Birth to mother with chronic HBV or HCV

10. Possible Risk Factors • Body piercing or tattooing • Multiple sexual partners or sexually transmitted diseases • Health care workers (HCV) • Contacts of HCV positive persons Source: NACB Laboratory Guidelines for Screening, Diagnosis, and Monitoring of Hepatic Injury. Dufour, Lott, Nolte, Gretch, Koff, Seeff

11. Fulminant Hepatitis • Syndrome in which severe liver dysfunction is accompanied by hepatic encephalopathy within 8 weeks • Causes include viral hepatitis (75%), chemical toxicity (acetaminophen, drug reactions, poisonous mushrooms, other poisons) • Complications include cerebral edema, coagulopathy, bleeding, cardiovascular complications, renal failure, pancreatitis

12. Chronic Hepatitis • At least 6-month course of hepatitis or biochemical and clinical evidence of liver disease with confirmatory biopsy findings of unresolving hepatic inflammation • Can be caused by autoimmune, viral, metabolic, or toxic etiologies

13. Alcoholic Liver Disease: Most Common Liver Disease • Alcohol excess and abuse • Most common cause of liver disease in the U.S. • Fourth leading cause of death among middle-aged Americans • Alcohol problems are highest among young adults, ages 18 to 29.

14. Stages of Alcoholic Liver Disease • Hepatic steatosis • Alcoholic hepatitis • Alcoholic (Leannec’s) cirrhosis

15. Alcoholic Liver Disease • Disease resulting from excessive alcohol ingestion characterized by fatty liver (hepatic steatosis), hepatitis, or cirrhosis • Most common liver disease in the U.S., except perhaps fatty liver secondary to obesity

16. Toxic Effects of Excess Alcohol Use

17. Alcoholic Liver DiseaseMetabolic Changes • Steatorrhea • Wernicke-Korsakoff syndrome • Peripheral neuropathy • Pellagrous psychosis • Folate deficiency

18. End-Stage Alcoholic Liver DiseasePossible Characteristics • Malnutrition • Portal hypertension with varices • Ascites • Hyponatremia • Hepatic encephalopathy • Glucose alterations

19. End-Stage Alcoholic Liver DiseasePossible Characteristics • Fat malabsorption • Osteopenia • Thrombocytopenia with anemia

20. Non-Alcoholic Steatohepatitis (NASH) • Histologically resembles alcoholic hepatitis • Most common cause of chronic hepatic injury other than viruses and alcohol; most common cause of cryptogenic cirrhosis • Commonly in middle-aged women with obesity and/or diabetes but appears in persons without these risk factors

21. Non-Alcoholic Steatohepatitis (NASH) • Patients with NASH often have abnormal lipid profiles • Differs from alcoholic hepatitis in that ALT is higher than AST except in cirrhosis • Weight loss may cause significant improvement in enzyme results; in one study a 1% reduction in weight caused an average fall of 8.1% in ALT • Biopsy is the only diagnostic procedure with adequate specificity

22. Cholestatic Liver Diseases Primary biliary cirrhosis (PBC) • An immune-mediated chronic cirrhosis of the liver due to obstruction or infection of the small and intermediate-sized intrahepatic bile ducts, whereas the extrahepatic biliary tree and larger intrahepatic ducts are normal • 90% of patients are women

23. Cholestatic Liver Diseases Sclerosing cholangitis • Fibrosing inflammation of segments of extrahepatic bile ducts, with or without involvement of intrahepatic ducts • May be an immune disorder • 50-75% of patients also have inflammatory bowel disease • 60-70% are men

24. Cholestatic Liver Diseases Sclerosing Cholangitis • Increased risk of fat soluble vitamin deficiencies due to steatorrhea • Hepatic osteodystrophy due to vitamin D and calcium malabsorption resulting in secondary hyperparathyroidism and osteomalacia or rickets • Treated with immunosuppressants

25. Inherited Disorders: Hemochromatosis • Inherited disease of iron overload • Store 20-40 g of iron in the liver compared with .3 to .8 g in normal persons • Causes hepatomegaly, esophageal varices, glucose intolerance • Treated by phlebotomy

26. Inherited Disorders: Wilson’s Disease • Autosomal recessive disorder associated with impaired biliary copper excretion • Copper accumulates in liver, brain, cornea, and kidneys • May present with neurological signs, Kayser-Fleischer rings, low serum ceruloplasmin, psychiatric symptoms • Always presents before age 40 • Treated with copper-chelating agents, zinc supplementation, low copper diet

27. Inherited Disorders: α1-antitrypsin deficiency • Causes cholestasis or cirrhosis and can cause liver and lung cancer • No treatment but liver transplant

28. Other Liver Diseases • Liver tumors • Systemic diseases (rheumatoid arthritis, systemic sclerosis) • Nonalcoholic steatohepatitis** • Acute ischemic and chronic congestive hepatopathy • Parasitic, bacterial, fungal, and granulomatous liver diseases

29. Normal Liver vs. Damaged Liver

30. Microscopic Image of (A) Normal Liver; (B) cirrhotic liver) (Adapted from Bray GA. Gray DS, Obesity, part 1: Pathogenisis. West J Med 149:429, 1988; and Lew EA, Garfinkle L; Variations in mortality by weight among 750,000 men and women. J Clin Epidemiol 32:563, 1979.) (From Kanel G, Korula J. Atlas of Liver Pathology. W.B. Saunders, 1992.)

31. Clinical Manifestations of Cirrhosis

32. Interpretation of Lab Data In Liver Disease

33. Liver Test Panel • Aspartate transaminase (AST) • Alanine aminotransferase (ALT) • Alkaline phosphatase (ALP) • Total bilirubin • Direct bilirubin • PT/PTT • Ceruloplasmin • Total protein • Albumin • Viral serologies

34. AST and ALT • Enzymes released into circulation following injury or death of cells in heart, liver, lungs, and other parts of the body • High AST (200 U/L) and ALT (300 U/L) are indicative of liver disease in presence of jaundice or non-specific symptoms of acute illness • Levels are higher in acute hepatic injury; lower in uncomplicated hepatitis and chronic liver disease • Transaminases relate more to cause of liver injury than prognosis

35. ALP (alkaline phosphatase) • Usually normal in acute and chronic liver disease • High levels are usually indicative of obstruction of biliary drainage

36. Bilirubin • Results from the breakdown of hemoglobin in the red blood cells and removal from the body by the liver, which excretes it in bile • Rises when the liver is unable to excrete bilirubin or when there is excessive destruction of red blood cells • In viral hepatitis, total bilirubin >257 micromoles/L indicates severe liver injury • In alcoholic hepatitis, bilirubin >428 micromoles/L predicts high likelihood of death

37. Two Forms of Bilirubin • Indirect or unconjugated bilirubin: is protein bound;  with increased destruction of red blood cells • Direct or conjugated bilirubin: not protein bound; circulates until it reaches the liver, where it is conjugated;  in dysfunction or blockage of the liver • Dx: first, measure total bilirubin; if that is high, measure direct and indirect • Reference values: Total: 0.3-1.0 mg/dL, or 5-17 micromoles/L • Conjugated: 0.0-0.2 mg/dL or 0.0-3.4 micromoles/L

38. Bilirubin Circulation

39. Hepatocellular Jaundice  direct (conj) bilirubin Injury or disease of the parenchymal cells of the liver caused by • Viral hepatitis • Cirrhosis • Infectious mononucleosis • Reactions of certain drugs such as chlorpromazine

40. Obstructive Jaundice Direct bilirubin • Obstruction of the common bile or hepatic ducts due to stones or neoplasms. • Causes high conjugated bilirubin levels due to bile regurgitation

41. Hemolytic Jaundice unconjugated bilirubin Overproduction of bilirubin resulting from hemolytic processes • After blood transfusions • Pernicious anemia • Sickle cell anemia • Transfusion reactions

42. Ceruloplasmin • Normal value: 25-63 mg/dL (250-630 mg/L) • Copper bound to ceruloplasmin constitutes the largest amount of Cu2+ in circulation • In Wilson’s disease Cu2+ mobilization from the liver is drastically reduced because of low production of ceruloplasmin • Values <14 mg/dL may be expected • However, low ceruloplasmin is not the primary defect in Wilson’s disease; some patients with Wilson’s are not low

43. Screening for Liver Disease • Asymptomatic high risk individuals should be screened for chronic hepatitis • ALT is the most cost-effective screening test for metabolic or drug-induced liver injury • AST should also be measured with hx of alcohol abuse (in alcoholic hepatitis AST is > ALT) • Individuals at high risk for viral hepatitis should be screened using specific viral serologies (HBsAg, anti-HCV, IgM anti-HAV, anti-HBS, HCV-RNA) in addition to ALT

44. Predictors of Prognosis • Prothrombin time: the most important predictor of prognosis; prolonged PTT indicative of poor prognosis • Albumin: serum albumin <2.5 g/dL indicates high risk of death

45. Lab Tests in Acute Liver Disease *upper reference limit Source: NACB Laboratory guidelines for screening, diagnosis, and monitoring of hepatic injury. Dufour, Lou, Nolic, Gretch, Koff, Seeff

46. Causes of Elevated ALT and/or AST Source: NACB Laboratory guidelines for screening, diagnosis, and monitoring of hepatic injury. Dufour, Lou, Nolic, Gretch, Koff, Seeff

47. Causes of Elevated ALT and/or AST

48. Causes of Elevated ALT and/or AST

49. Body weight Anthropometric measurements Creatinine-height index Nitrogen balance studies Visceral protein levels Immune function tests Interpretation of Nutrition Assessment Tests in Patients with End-Stage Liver Disease

50. SGA Parameters for Nutritional Evaluation of Liver Transplant Candidates • History • Weight change (fluid changes) • Appetite • Taste changes and early satiety • Dietary recall (calories, protein, sodium) • Persistent gastrointestinal problems (nausea, vomiting, diarrhea, constipation, difficulty chewing or swallowing)