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 HEPATITIS What is it? Chronic non-septic inflammatory disease of the liver which has many different causes

10. CHRONIC HEPATITIS What the clinician needs to know Breed predisposition

11. CHRONIC HEPATITIS What the clinician needs to know Breed predisposition Clinical signs – chronic illness

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

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

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

15. CHRONIC HEPATITIS What the clinician needs to know Breed predisposition Clinical signs (or lack there of) Absolute necessity of biopsy

16. WHAT DO YOU DO AFTER DIAGNOSING CHRONIC HEPATITIS?

17. Drugs That Cause Hepatic Disease Corticosteroids

18. Drugs That Cause Hepatic Disease CorticosteroidsAcetaminophen PhenobarbitalPrimidone Sulfa drugsCarprofen

19. Drugs That Cause Hepatic Disease CorticosteroidsAcetaminophen PhenobarbitalPrimidone Sulfa drugsCarprofen AmiodaroneItraconazole KetoconazoleDiazepam Doxycycline Methimazole AzathioprinePhenytoin Mibolerone Griseofulvin Mitotane Stanozolol Mebendazole Clavamox ClindamycinCimetidine

20. CHRONIC HEPATITIS Causes Drugs – You REALLY want to catch this BEFORE biopsy – sometimes easy to establish cause and effect – sometimes hard to establish cause and effect

25. CHRONIC HEPATITIS Copper-associated hepatic disease Bedlington terrier West Highland white terriers Doberman pinschers Skye terrier Dalmations Labrador retrievers

26. CHRONIC HEPATITIS Causes 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 HEPATITIS Therapy 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 HEPATITIS Therapy 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 HEPATITIS Therapy 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. 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 HEPATOPROTECTIVE THERAPY

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

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

37. CHRONIC HEPATITIS Prognosis Potentially ominous signs: – ascites – icterus – severe hypoalbuminemia – apparent cirrhosis – hepatic encephalopathy

38. CHRONIC HEPATITIS Prognosis < 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 GUIDANCETYPE OF BIOPSY BlindFine needle aspirate Ultrasound

51. TAMU# 72927 Sig: 9 yr M(c) Cat6 kg CC: Weight loss & vomiting HPI: Poor appetite & vomiting bile for 6 weeks; has lost 2.3 kg ALT = 202 U/L SAP = 427 U/L PE: No significant findings

52. TAMU# 72927 Cytology of liver (ultrasound guided): “no cytologic evidence of active inflammation or neoplasia … mild hepatic lipidosis”

53. TAMU# 72927 Histopathology: “Moderate to severe multifocal lymphocytic cholangiohepatitis with cholestasis; mild hepatic lipidosis”

55. Hepatic Biopsy GUIDANCETYPE OF BIOPSY BlindFine needle aspirate UltrasoundCore needle

57. “Diagnostic Accuracy of Tru Cut Needle Biopsy Compared to Wedge Biopsy of the Liver” by Cole et al, JAVMA 220:1483, 2002 100 dogs and 22 cats 51.6% discordance between results

60. Hepatic Biopsy GUIDANCETYPE OF BIOPSY BlindFine needle aspirate UltrasoundCore needle LaparoscopyWedge Surgery

64. TAMU#162500 Abdominal U/S:“The liver, pancreatic region, GI tract, kidneys and adrenals were unremarkable.”

66. TAMU#139804 Abdominal U/S:“The liver and spleen were unremarkable.... Essentially normal abdominal ultrasound.”

68. TAMU#128604 Abdominal U/S:“A sonographic examination of the abdomen was performed and revealed no significant abnormal findings”

70. TAMU#168184 Abdominal U/S:“... sludge within the gall bladder. This was organizing and probably the early development of a cholelith. The remainder of the liver was considered normal... Changes in the gall bladder consistent with sludge and possibly early cholelith development. Otherwise, normal abdomen. ”

72. TAMU#147332 Abdominal U/S:“The liver appeared to be of normal size, texture and echogenicity.... Essentially normal abdominal ultrasound.”

74. Ultrasound and the Liver 40% (dog) to 60% (cat) accurate in diffuse hepatic diseases Cannot distinguish benign from malignant nodules

76. Modified laparoscopy JAVMA 187:1032, 1985

78. Sterile Not sterile

79. Sterile towel