TAMU #81095

2. TAMU #81095 Sig: 11 yr M(c) Mixed Labrador CC: Chronic cough HPI: Cough and expectoration started 1 week ago Vet found hypoalbuminemia on routine blood work PE: Thin but normal

3. TAMU #81095 PCV = 33% (35-54) WBC = 11,100/ul (6,-17,000) Segs = 9,102/ul (3,-12,000) Bands = 0/ul (< 500) Lymphs = 444/ul (1,-5,000) Platelets = 187,000/ul (200,-500,000)

4. TAMU #81095 BUN = 6 mg/dl (6-20) Creatinine = 0.6 mg/dl (< 2.0) Cholesterol = 51 mg/dl (120-247) Glucose = 81 mg/dl (60-120) Total protein = 5.8 gm/dl (5.5-7.5) Albumin = 1.8 gm/dl (2.5-4.4) ALT = 649 IU/L (< 110) SAP = 320 IU/L (< 130) Bilirubin = 0.1 mg/dl (< 1.0)

5. TAMU #81095 Abdominal ultrasound: “No significant findings”

6. IS IT COST-EFFECTIVE OR PRACTICAL TO BIOPSY THE LIVER OF AN ASYMPTOMATIC DOG JUST BECAUSE IT HAS INCREASED HEPATIC ENZYMES?

7. TAMU #81095 Hepatic biopsy: SEVERE chronic hepatitis with marked fibrosis and scarring; early cirrhotic changes

9. CHRONIC HEPATITISWhat is it? • Chronic non-septic inflammatory disease of the liver which has many different causes

10. CHRONIC HEPATITISWhat the clinician needs to know • Breed predisposition

11. CHRONIC HEPATITISWhat the clinician needs to know • Breed predisposition • Clinical signs • chronic illness

12. CHRONIC HEPATITISWhat the clinician needs to know • Breed predisposition • Clinical signs • chronic illness • asymptomatic dog with lab changes • acute illness

13. CHRONIC HEPATITISWhat the clinician needs to know IMPORTANCE OF THE WORD “CHRONIC”

14. One year ago, they found an increased ALT, so they decided to watch and see what would happen ... TAMU #149538

15. CHRONIC HEPATITISWhat the clinician needs to know • Breed predisposition • Clinical signs (or lack there of) • Absolute necessityof biopsy

16. WHAT DO YOU DO AFTER DIAGNOSING CHRONIC HEPATITIS?

17. Drugs That Cause Hepatic Disease Corticosteroids

18. Drugs That Cause Hepatic Disease CorticosteroidsAcetaminophen Phenobarbital Primidone Sulfa drugs Carprofen

19. Drugs That Cause Hepatic Disease CorticosteroidsAcetaminophen Phenobarbital Primidone Sulfa drugs Carprofen Amiodarone Itraconazole Ketoconazole Diazepam Doxycycline Methimazole Azathioprine Phenytoin Mibolerone Griseofulvin Mitotane Stanozolol Mebendazole Clavamox Clindamycin Cimetidine

20. CHRONIC HEPATITISCauses • Drugs • You REALLYwant to catch this BEFOREbiopsy • sometimes easy to establish cause and effect • sometimes hard to establish cause and effect

25. CHRONIC HEPATITISCopper-associated hepatic disease Not that easy!!! • Bedlington terrier • West Highland white terriers • Doberman pinschers • Skye terrier • Dalmations • Labrador retrievers

26. CHRONIC HEPATITISCauses • Copper intoxication • primary (causes hepatic disease – genetic) • Innocent copper accumulation • secondary (caused by hepatic disease)

27. TAMU #170148 Centrilobular (zone 3) deposits of copper strongly suggest that copper is the cause of the problem

28. CHRONIC HEPATITISTherapy for inflammation/necrosis • Remove cause – symptomatic • Chelate copper with d-Penicillamine (10-15 mg/kg bid, give with food) • Do not give zinc when administering copper chelators

29. CHRONIC HEPATITISTherapy for inflammation/necrosis • Remove cause – not symptomatic • Decrease copper absorption with zinc gluconate (10 mg elemental zinc/kg) • Administer with tuna fish • Measure blood zinc levels • need > 200 mcg/dl to be therapeutic • > 2,000 mcg/dl may cause hemolysis

30. CHRONIC HEPATITISTherapy for inflammation/necrosis Decrease the inflammatory response • Corticosteroids • prednisolone (not prednisone) • budesonide • Cytotoxic drugs (azathioprine) • Cyclosporine

31. HEPATOPROTECTIVE THERAPY • What this therapy does NOT do ... • What this therapy does do ...

32. HEPATOPROTECTIVE THERAPY • Ursodeoxycholic acid (15 mg/kg qd) • A hydrophilic bile acid • Displaces toxic, hydrophobic bile acids • Hydrophobic bile acids are detergents • damage hepatocyte & mitochondrial membrane • Food enhances bioavailability

35. HEPATOPROTECTIVE THERAPY • s-adenosyl L-Methionine (SAMe) • Human studies • acute intrahepatic cholestasis • alcoholic liver disease • Veterinary studies • healthy animals • acetaminophen, prednisolone

36. HEPATOPROTECTIVE THERAPY • Milk thistle (Silymarin) • Silybin is the active fraction • Antioxidant, antifibrotic, anti-inflammatory • Effective for Amanita, aflatoxin, acetaminophen, ethanol, ischemic damage

37. CHRONIC HEPATITISPrognosis • Potentially ominous signs: • ascites • icterus • severe hypoalbuminemia • apparent cirrhosis • hepatic encephalopathy

38. CHRONIC HEPATITISPrognosis • < 4 months for those with poor prognostic signs • > 1.5 years for others

39. WHAT ABOUT THE “NORMAL” DOG THAT HAS AN INCREASED ALT?

42. WHAT ABOUT THE “NORMAL” DOG THAT JUST HAS AN INCREASED SAP?

46. WHAT ABOUT SCOTTISH TERRIERS?

47. TAMU #96276 Sig: 4 yr M Cocker Spaniel CC: Swollen abdomen HPI: Dark yellow urine and depression were first noted by owners 2 days ago Today the dog has an obviously swollen abdomen PE: Depressed and has ascites

48. TAMU #96276 BUN = 57 mg/dl (8-29) Creatinine = 2.4 mg/dl (< 2.0) Sodium = 128 mEq/L (138-148) Potassium = 4.9 mEq/L (3.5-5.0) Total protein = 6.5 gm/dl (5.5-7.0) Albumin = 2.0 gm/dl (2.5-4.4) ALT = 72 IU/L (< 130) SAP = 128 IU/L (< 147) Bilirubin = 1.6 mg/dl (< 0.8)

50. Hepatic Biopsy GUIDANCE TYPE OF BIOPSY Blind Fine needle aspirate Ultrasound