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Hepatic Diseased Revised Keynote

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Hepatic Diseased Revised Keynote

  1. 1. Hepatic Disease Clinical Medicine I Patrick Carter MPAS, PA-C February 14, 2011
  2. 2. Objectives Discuss the major metabolic functions of the liver. Identify the categories of viral agents that cause hepatitis. For each of the following, describe the etiology, risk factors, transmission, clinical features, diagnostic findings, treatment, and prophylaxis: ◦ HAV ◦ HBV ◦ HCV ◦ HDV ◦ HEV ◦ HGV Discuss the possible complications of viral hepatitis.
  3. 3. Objectives Differentiate between toxic and drug induced injury of the hepatic system. Define autoimmune chronic active hepatitis. Identify the typical clinical presentation of alcoholic liver disease. Identify the pathophysiologic mechanisms of alcohol injury to the liver.
  4. 4. Objectives Identify the typical treatment options for alcoholic liver disease including pharmacological, dietary, and life style treatments Discuss the association between alcoholic liver disease and portal hypertension. State the major complications of alcoholic liver disease including presentation, laboratory findings, and treatment of: spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy Indicate the prognosis for alcoholic liver disease.
  5. 5. Assessment Parameters Acute or chronic Focal or diffuse Mild or severe Reversible or irreversible Fulminant – development of hepatic encephalopathy within 8 weeks Sub-fulminant -- development of hepatic encephalopathy at 8 weeks – 6 months
  6. 6. Definitions Jaundice (Icterus) ◦ Yellow pigmentation of skin & sclera secondary to increased serum bilirubin Bilirubin ◦ Yellow breakdown product of normal heme catabolism Unconjugated (Indirect) bilirubin ◦ Heme is turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. It is then bound to albumin and sent to the liver. Conjugated (Direct) bilirubin ◦ In the liver bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase. Much of it goes into the bile and thus out into the small intestine Hepatitis ◦ Inflammation of the liver Cirrhosis ◦ Scarring and fibrosis of liver secondary to chronic liver disease
  7. 7. Hepatic Physiology Energy metabolism ◦ carbohydrates, lipid and protein ◦ glucose production ◦ cholesterol synthesis Protein synthesis functions ◦ plasma proteins (albumin, clotting factors)
  8. 8. Hepatic Physiology Solubilization, transport, and storage ◦ drug and poison detoxification ◦ solubilization of fats and fat-soluble vitamins ◦ synthesis of VLDL, HDL, LDL ◦ uptake and storage of Vit A, D, B12 and Folate
  9. 9. Hepatic Physiology Protective and clearance functions ◦ detox of ammonia ◦ detox of drugs ◦ clearance of damaged cells and proteins, hormones, drugs and clotting factors ◦ clearance of bacteria and antigens
  10. 10. Etiology of Hepatic Disease Cholelithiasis Excessive alcohol intake Inherited disorders Viruses/bacterial Infection Medications Cirrhosis Cancer
  11. 11. Jaundice (Icterus)
  12. 12. Causes of Jaundice CMDT 2011 Chapter 16
  13. 13. JaundicePathology Smart Charts, Groysman; McGraw-Hill. 2001
  14. 14. Acute Hepatic Failure Fulminant ◦ Hepatic encephalopathy within 8 weeks after onset of acute Liver Disease Subfulminant ◦ Hepatic encephalopathy between 8 weeks and 6 months after onset of acute Liver Disease
  15. 15. Acute Hepatic Failure Causes ◦ Acetaminophen toxicity is most common accounting for at least 45% ◦ Idiosyncratic drug reactions 2nd most common ◦ Viral Hepatitis (only 12% of all cases) ◦ Poisonous mushrooms ◦ Shock ◦ Hyperthermia / Hypothermia ◦ Budd-Chiari syndrome ◦ Malignancies ◦ Wilson disease
  16. 16. Acute Hepatic Failure Risk of acute hepatic failure is increased in patients with diabetes Outcome is worsened by obesity Symptoms & Signs ◦ Gastrointestinal ◦ SIRS ◦ Hemorrhagic phenomena ◦ Adrenal insufficiency ◦ Subclnical myhocardial injury
  17. 17. Acute Hepatic Failure Labs ◦ Serum aminotransferase levels are elevated (>5000 in acetaminophen tox) ◦ Bilirubin may be normal or minimally elevated initially then elevates as progresses ◦ Serum ammonia elevated – correlates with encephalopathy & intracranial hypertension
  18. 18. Acute Hepatic Failure
  19. 19. Acute Hepatic Failure Treatment ◦ Correct coagulation defects ◦ Correct electrolyte defects ◦ Correct acid-base disturbances ◦ Correct hypoglycemia ◦ Correct encephalopathy (lactulose) ◦ Prophylactic antibiotics not routinely recommended (only Sepsis) ◦ Steroids are uncertain in value ◦ Stress gastrophathy prophylaxis
  20. 20. Acute Hepatic Failure Treatment ◦ Treat intracranial hypertension (Mannitol) ◦ Administer acetylcysteine for acetaminophen toxicity ◦ EARLY transfer to liver transplantation center is crucial
  21. 21. Acute Hepatic Failure Prognosis ◦ Mortality up to 80% - except acetaminophen toxicity ◦ Acetaminophen toxicity up to 65% transplant free survival ◦ Be familiar with poor prognostic indicators for acetaminophen and non-acetaminophen hepatotoxicity in CMDT (page 608)
  22. 22. Acute Viral Hepatitis
  23. 23. Viral Hepatitis Essentials of diagnosis ◦ Prodrome of anorexia, nausea/vomiting, malaise, aversion to smoking ◦ Fever, enlarged and tender liver, jaundice ◦ Normal to low WBCs, markedly elevated aminotransferases early in the course ◦ Liver biopsy rarely indicated, but might show hepatocellular necrosis
  24. 24. Acute Viral Hepatitis Symptoms ◦ Icteric phase – jaundice after 5-10 days ◦ Convalescent phase – gradual disappearance of symptoms Signs ◦ Hepatomegaly ◦ Liver tenderness ◦ Splenomegaly in about 15% of cases
  25. 25. Hepatitis A Virus (HAV) Fecal/oral transmission Poor sanitation or crowded living situations Contaminated water & food ~ 30 days incubation Low level of mortality Fulminant cases are rare Never chronic
  26. 26. Hepatitis B Virus (HBV) Blood and blood products Sexual transmission Maternal-fetal transmission Prevalent in homosexuals and IV drug users Incidence has decreased by 75% since the 1980’s Onset is more insidious than HAV
  27. 27. Hepatitis B Virus (HBV) 6 week – 6 month incubation Aminotransferase levels higher than in HAV Risk of fulminant hepatitis is less than 1% but has a 60% mortality rate Infection persists in 1-2%, higher in immunocompromised
  28. 28. Hepatitis B Virus (HBV) Patients with chronic HBV have substantial risk of cirrhosis and hepatocellular carcinoma (up to 40%) HBsAg – first evidence of infection Anti-HBs – signals recovery from HBV infection and immunity Vaccination exists
  29. 29. Hepatitis B Virus (HBV) CMDT 2011 Chapter 16
  30. 30. Hepatitis C Virus (HCV) Transmission ◦ IV drug use ◦ Body piercings ◦ Blood transfusion Low risk of transmission ◦ Sexual ◦ Maternal/fetal
  31. 31. Hepatitis C Virus (HCV) 30 – 50% of HIV patients are coinfected with HCV ◦ Faster progression of chronic HCV to cirrhosis Incubation period is 6-7 weeks Clinical illness is generally mild or asymptomatic 80% will become chronic
  32. 32. Hepatitis C Virus (HCV) Screening to detect HCV antibodies Confirmation by an assay for HCV RNA About 20% of patients infected with HCV will clear the infection No vaccination available Treatment exists with varying results
  33. 33. Hepatitis D (Delta agent) Defective RNA virus that causes hepatitis ONLY in association with HBV Usually percutaneous exposure As superinfection with HBV, may cause fulminant hepatitis or severe chronic hepatitis In US, occurs mainly in IV drug users 3 x risk of hepatocellular carcinoma
  34. 34. Hepatitis E (HEV) Rare in the US Endemic areas are India, Burma, Afghanistan, Algeria and Mexico Waterborne Illness is self-limited Mortality rate of 10-20% in pregnant women
  35. 35. Hepatitis G (HGV) Percutaneously transmitted and associated with chronic viremia lasting at least 10 years Has been detected in ◦ 1.5% of blood donors ◦ 50% of IV drug users ◦ 30% of hemodialysis patients ◦ 20% of hemophiliacs ◦ 15% of patients with chronic hepatitis B or C
  36. 36. Hepatitis G (HGV) Does not cause important liver disease Does not affect the response of patients with chronic hepatitis B or C to antiviral therapy HGV coinfection may improve survival in patients with HIV infection
  37. 37. Viral Hepatitis Symptoms ◦ Prodromal phase  General malaise, myalgia, arthralgia, fatigue and anorexia  Distaste for smoking  Nausea/vomiting  Serum sickness in HBV  Fever, usually low-grade  RUQ or epigastric pain, usually mild
  38. 38. Acute Viral Hepatitis Prevention ◦ Thorough handwashing ◦ Universal precautions ◦ Screening of blood supply ◦ Vaccinations  HAV – close contacts of infected patients, persons traveling to endemic areas  HBV – universal vaccination of infants and children, healthcare workers
  39. 39. Chronic Viral Hepatitis Defined as chronic necroinflammation > 3-6 months Causes ◦ Hepatitis B ◦ Hepatitis C ◦ Hepatitis D ◦ Autoimmune Hepatitis ◦ Alcoholic & Non Alcoholic Hepatitis ◦ etc… Prognosis is variable depending upon disease
  40. 40. Chronic Hepatitis B 4 Phases 1. Immune Tolerant 2. Immune Clearance 3. Inactive Carrier State 4. Reactivated Chronic Hepatitis B
  41. 41. Chronic Hepatitis B Risk Factors ◦ Male ◦ Increased Age ◦ ETOH Use ◦ Cigarrette Use ◦ Coinfection with:  HBV +/- HDV, HCV, autoimmune hepatitis, Wilson’s disease, etc. ◦ HIV with low CD4 count
  42. 42. Chronic Hepatitis B Treatment ◦ Peginterferion alpha 2a  4 years for treatment  Injections weekly  Increased survival 40% ◦ Oral Nucleosides & Nucleoside Analogues  Entecavir = 1st line choice  Decreased resistance  Orally administered  Up to 70-80% supression
  43. 43. Chronic Hepatitis C Develops in up to 85% with Acute HCV About 20% will progress to cirrhosis in 20 years Men with EtOH use more than 50 g/day increases risk of cirrhosis Age > 40 when acquire HCV increases risk Tobacco & Cannabis increases risk African Americans have increase rate of Chronic HCV but less fibrosis (poor responders)
  44. 44. Chronic Hepatitis C Treatment ◦ Age less than 70 with minimal fibrosis ◦ Combination therapy with peginterferon alpha 2a or 2b and ribavirin ◦ Response rates up to 55-80% ◦ May reduce the risk of hepatocellular carcinoma ◦ Mexican American & African American are poor responders to therapy
  45. 45. Autoimmune Hepatitis Young – middle aged women Increased Risk for Cirrhosis & Carcinoma Signs/Symptoms ◦ Healthy Appearance ◦ Multiple spider nevi ◦ Cutaneous striae ◦ Acne ◦ Hirsutism ◦ Hepatomegaly ◦ Amenorrhea
  46. 46. Autoimmune Hepatitis Associated Disease ◦ Arthritis ◦ Sjogren’s syndrome ◦ Thyroiditis ◦ Nephritis ◦ Ulcerative colitis ◦ Coombs (+) Hemolytic Anemia
  47. 47. Autoimmune Hepatitis Labs ◦ AST/ALT > 1000 ◦ Elevated Total bilirubin ◦ Positive ANA/Smooth Muscle Antibody ◦ May cause FALSE positive Anti-HCV Liver biopsy needed to establish diagnosis and evaluate severity and need for treatment
  48. 48. Autoimmune Hepatitis Treatment ◦ If Asymptomatic with Normal LFT no Treatment indicated ◦ If Asymptomatic with abnormal LFT or Symptomatic then:  Prednisone  (+) Azathioprine ◦ Response rate up to 80% with combination ◦ Fibrosis may reverse with treatment and rarely progresses ◦ Non-responders may need other meds or transplant
  49. 49. Drug & Toxin Induced Liver Disease1. Direct hepatic toxins ◦ Dose related severity ◦ Latent period following exposure ◦ Susceptibility in all individuals ◦ Examples  Acetaminophen, EtOH, carbon tetrachloride, chloroform, heavy metals, mercaptopurine (6-MP), tetracycline, vitamin ANote: Statins may cause elevation ofaminotransferase but rarely cause hepatitis and areNO LONGER contraindicated in liver disease
  50. 50. Drug & Toxin Induced Liver Disease2. Drug induced idiosyncratic reactions ◦ Sporadic ◦ Not dose associated ◦ Occasionally features suggest allergic reaction (fever and eosinophilia) ◦ Examples  Amiodarone, ASA, carbamazepine, chloramphenicol, diclofenac, halothane, isoniazid, ketoconazole, phenytoin, etc.
  51. 51. Drug & Toxin Induced Liver Disease3. Cholestatic Reactions ◦ Drug induced cholestasis ◦ Drug induced inflamation of portal arewas with bile duct injury ◦ Often associated with allergic features4. Acute or Chronic Hepatitis ◦ Result in acute or chronic hepatitis ◦ Histologically & Clinically indistinguishable from autoimmune hepatitis
  52. 52. Alcoholic Hepatitis Acute or chronic inflammation and parenchymal necrosis of the liver induced by EtOH Often Reversible Most common cause of cirrhosis in the US Tumor necrosis factor alpha and acetaldehyde induces immune response to proteins in liver
  53. 53. Alcoholic Hepatitis Frequency estimated at 10-15% of daily drinkers (more than 50 g) for over 10 years 50 g = 4 drinks (4 oz. 100 proof whiskey, 15 oz. wine or 48 oz. beer) Women > men Concurrent HBV or HCV increases risk
  54. 54. Alcoholic Hepatitis Signs and symptoms ◦ Asymptomatic to Rapidly Fatal Acute Illness ◦ Enlarged liver ◦ Anorexia and nausea ◦ Hepatomegaly and jaundice ◦ Abdominal pain ◦ Splenomegaly ◦ Ascites ◦ Fever ◦ Encephalopathy
  55. 55. Abdominal pain
  56. 56. RecentHeavy Abdominal painDrinking SplenomegalyAnorexia AscitesNausea FeverHepatomegaly EncephalopathyJaundice
  57. 57. Treatment Strict EtOH abstinence - ESSENTIAL Caloric supplement and nutritional support Vitamin supplement – folic acid and thiamine Glucose administration increases Vitamin B1 needs and can precipitate Wernicke- Korsakoff syndrome – must co-administer thiamine
  58. 58. Alcoholic Hepatitis Labs ◦ Mild elevation of AST < 300 ◦ AST > ALT at least 2 fold ◦ Alk Phos mildly elevated < 3 times normal ◦ Increased Total Bilirubin in 60-90% ◦ Macrocytic Anemia ◦ 10% may have Thrombocytopenia If Total Bili > 10 and INR > 6 = Poor Prognosis with up to 50% mortality
  59. 59. Alcoholic Hepatitis Differential ◦ Mimics  Cholecystitis  Cholelithiasis  Drug induced hepatitis
  60. 60. Treatment Stop ETOH Nutritional Support Prednisone 32 mg/day for 1 month ◦ May reduce short-term mortality for patients with alcoholic hepatitis and encephalopathy or greatly elevated bilirubin Pentoxifylline 400 mg TID for 4 weeks may decrease risk of hepatorenal syndrome
  61. 61. Treatment Liver transplant ◦ Usually requires abstinence for 6 months prior to transplant ◦ Absolute contraindications  Malignancy, advanced cardiopulmonary disease and sepsis ◦ Relative contraindications  Age > 70, HIV infection, portal vein thrombosis, active substance abuse, severe malnutrition
  62. 62. Cirrhosis 12th Leading Cause of Death in U.S. Hepatocellular injury that leads to: ◦ Fibrosis ◦ Nodular Regeneration Risk Factors ◦ Chronic Viral Hepatitis ◦ Alcoholic Hepatitis ◦ Drug Toxicity ◦ Autoimmune Hepatitis
  63. 63. Cirrhosis Clinical Features are Secondary to: ◦ Portal HTN ◦ Hepatic Cell Dysfunction ◦ Portosystemic Shunting
  64. 64. Portal HypertensionPathology Smart Charts, Groysman; McGraw-Hill. 2001
  65. 65. Signs of Portal HTN
  66. 66. Major Complications Ascites ◦ Diagnostic paracentesis indicated for new ascites  Cell count and culture  Albumin level ◦ Restriction of dietary sodium and fluid intake ◦ Diuretics – spironolactone +/- Lasix ◦ Large-volume paracentesis (4-6 L) ◦ TIPS (transjugular intrahepatic portosystemic shunt
  67. 67. Major Complications Spontaneous bacterial peritonitis ◦ Abdominal pain, increasing ascites, fever and progressive encephalopathy ◦ Paracentesis shows high WBC count ◦ Cultures are usually positive – most common E. coli or pneumococci
  68. 68. Major Complications Spontaneous bacterial peritonitis ◦ Treatment with IV cefotaxime 2 g q 8-12 hours for 5 days ◦ Overall mortality rate is up to 70% in 1 year Hepatorenal syndrome ◦ Azotemia in the absence of shock or significant proteinuria in a patient with end- stage liver disease
  69. 69. Major Complications Hepatorenal syndrome ◦ Does not improve with IV isotonic saline ◦ Oliguria and hyponatremia ◦ Diagnosis of exclusion ◦ Cause is unknown ◦ Treatment is generally ineffective ◦ Mortality is high without liver transplant ◦ TIPS procedure may buy time until transplant
  70. 70. Major Complications Hepatic encephalopathy ◦ Disordered CNS function due to failure of the liver to detoxify noxious agents originating in the gut ◦ Ammonia is most readily identified ◦ Dietary protein withheld during acute episodes ◦ Lactulose to acidify colon contents NH4+ NH3 + H+
  71. 71. Major Complications Hepatic encephalopathy ◦ NH4+ is not absorbable ◦ Lactulose should be dosed at 30 mL 3 or 4 times daily ◦ Avoid opioids and sedatives that are metabolized or excreted by the liver ◦ Zinc deficiency should be corrected if present
  72. 72. Prognosis Points Class One year survival Two year survival 5-6 A 100% 85% 7-9 B 81% 57% 10-15 C 45% 35%
  73. 73. Non-Alcoholic Fatty Liver Disease(NAFLD) Up to 30% US population Etiology ◦ Obesity ◦ Diabetes ◦ Hypertriglycerides ◦ Corticosteroids Physical Activity protects against NAFLD Don’t worry about NASH
  74. 74. Non-Alcoholic Fatty Liver Disease(NAFLD) Signs & Symptoms ◦ Asymptomatic ◦ Mild Right Upper Quadrant Pain ◦ Hepatomegaly (up to 75%) Chronic Liver Disease uncommon
  75. 75. Non-Alcoholic Fatty Liver Disease(NAFLD) Laboratory Findings ◦ Mild elevated Aminotransaminases & Alkaline Phosphatase levels ◦ Ratio ALT to AST > 1 (opposite ETOH) ◦ Ratio does decrease if fibrosis/cirrhosis develop Imaging ◦ CT/MRI/US demonstrate fatty liver ◦ Does not distinguish hepatitis
  76. 76. Non-Alcoholic Fatty Liver Disease(NAFLD) Liver Biopsy ◦ Percutaneous ◦ Diagnostic & “Standard Approach” ◦ Assess degree of inflammation & fibrosis BARD Score used to predict advanced fibrosis
  77. 77. Non-Alcoholic Fatty Liver Disease(NAFLD) Treatment ◦ Remove offending factors ◦ Weight Loss ◦ Exercise ◦ Fat Restriction ◦ Gastric Bypass with BMI > 35 Statins are NOT contraindicated
  78. 78. Questions?

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