Practical Internal Medicine

Liver Disease

Wendy Blount, DVM

Nacogdoches, TX

Liver Disease

Asymptomatic Elevated Liver Enzymes

Chronic Liver Disease

Acute Liver Failure

Elevated Liver Enzymes in the Well Pet

Cats are not little dogs• Cats with persistently elevate enzymes should be

worked up – T1/2 of liver enzymes hours, not days as in the dog

– cats have 1/3 the liver SAP compared to dogs

• Cats with significant cholangiohepatitis can have normal liver enzymes

• GGT elevated significantly exceeds SAP elevation only in hepatic lipidosis

• High bile acids in the cat indicates liver disease nearly 100% of the time

• Any bilirubinuria in the cat is significant– Can be used to monitor cholestatic disease

Elevated Liver Enzymes in the Well PetDogs… Grrrr…1. Explore the history for untreated problems

2. Treat empirically for reactive hepatopathy first• Treat problems that can insult the liver

– Occult infections – urinary, metritis, prostatitis, etc.

• Treat for sublinical cholangiohepatitis– Amoxicillin 10 mg/lb PO BID x 3 weeks

• Put on a supplement to curtail damage by hepatic inflammation

– Denosyl, Denamarin – dosage chart in package– Milk thistle

Elevated Liver Enzymes in the Well Pet

Milk Thistle• Dried herb: 15-20mg/lb SID (1.5-3% silymarin)• Concentrated extract: 2-5 mg/lb BID (70-

80% silymarin)• Alcohol concentrated extract: 2-5 mg/lb BID-

TID (70-80% silymarin)

• NOTE:NOTE: some extracts are whole herb extracts, and these are hard to dose high enough to be effective

Elevated Liver Enzymes in the Well Pet3. Recheck Liver enzymes in 30 days

4. Proceed with further diagnostics for liver disease

– Assess liver function with bile acids– Abdominal ultrasound and liver cytology– ACTH stimulation if signs of Cushing’s Disease

5. If Step 4 reveals significant undiagnosed problems, consider liver biopsy or referral for splenic portagram to rule out PSS

– Ultrasound guided liver biopsy (50% diagnostic)– Surgical liver biopsy

Scotties can have very high liver enzymes with no pathology

Undiagnosed Problems Causing Reactive Hepatopathy

• Occult infection– Urinary tract– Metritis, prostatitis

• Dental Disease• Disease of organ drained by portal vein• Severe muscle disease• Hypoxia – heart failure, respiratory disease,

severe anemia

Other Problems Causing Elevated SAP with normal ALT

• Bone growth or osteolysis– Puppies and kittens– Bone neoplasia– Osteomalacia– Hyperparathyroidism

• GI Disease• Pregancy• Kidney Disease• Drug Therapy

Pattern Recognition - Liver Disease• High liver enzymes

– ALT – hepatocellular disease– SAP, GGT – cholestasis– Can be normal with prolonged chronic disease

• Low albumin• Low fasting glucose• High prost-prandial glucose• Low BUN• Abnormal cholesterol, triglycerides• Ammonium biurate crystalluria• Prolonged recovery from anesthesia

Pattern Recognition - Liver Disease• Ascites – transudate or modified transudate

– Increased sodium retention, portal hypertension, hypoalbuminemia

• PU-PD• Acholic feces• Dark urine (orange) precedes icterus• Icterus

– Suspect if high bili with normal PCV

– Seen best on sclerae, penile mucosa, soft palate, under the tongue

– Icterus occurs when 10% of liver function remains

– Look for cholestatic disease if signficant bilirubinemia without bilirubinuria (delta bili)

Pattern Recognition - Liver Disease• Tendency to sepsis

– Hepatic RE system detoxifies blood from the gut (portal circulation)

• GI hemorrhage death spiral– Decreased hepatic clearance of gastrin– Factor’s, AT3 not produced adequately– Increased bile acids stimulated HCl secretion– DIC– Bleeding exacerbates hepatic encephalopathy– Large bleed can cause depletion coagulopathy

• Hemorrhage elsewhere only when near death– Petecheia, bruising, bleeding into cavities

Pattern Recognition - Liver Disease

• PSS in Cats– Salivation – most common clinical sign– Hepatic encephalopathy– Vomiting and diarrhea

Bile Acids

1. 12 hour fast – red top tube

2. Feed 1-2 Tablespoons a/d

3. 2 hour post prandial red top tube

If not fasted, doing only the post-prandial can be a good screen for liver insufficiency

Can’t run bile acids on a lipemic sample

Overfeeding can induce HE

Bile Acids

High bile acids in the blood can cause gastric hyperacidity in the stomach and diarrhea

Bile acids >30-40 umol/L in the dog and >20-30 umol/L in the cat warrant further investigation

Idexx SNAP test tells you • <12 umol/L• 12-25 umol/L• >25 umol/L

Ammonia

Normal in the dog 20-80 ug/dl

Normal in the cat 20-120 ug/dl

Elevated resting ammonia is significant

Idexx VetTest/Catalyst does ammonia assays

Falsely increased by hemolysis

Centrifuge and decant within 30 minutes

Run assay within 2 hours

Sending to outside lab can be difficult

Ammonia

Ammonia Tolerance Test:

1. 12 hour fast – red top tube

2. NH3Cl capsules 45 mg/lb max dose 3g PO

3. 30 minutes later – red top tube

Increase should be <32%

100% sensitive for PSS

DO NOT GIVE NH3Cl if resting ammonia elevated

• Can induce HE

Chronic Liver Disease

DDx Chronic Liver DiseaseImmune Mediated Cholangiohepatitis

• Westie, Doberman, Skye terrier, cats

Copper Storage Disease• Dobermans, Bedlingtons

Portosystemic Shunt• Congential or Acquired

• Extrahepatic – Yorkie, schnauzer, poodle, dachshund• Intrahepatic – Doberman, Golden, Lab, Irish Setter,

Samoyed, Irish Wolfhound

Microvascular Dysplasia• Yorkie, Cairn Terrier

DDx Chronic Liver DiseaseBacterial Cholangiohepatitis

• cats

Fungal Hepatitis

Heterobilharzia americanum

Chronic Liver Disease usually Diagnosed

by Liver Biopsy

Tx Chronic Liver DiseaseProper Diet

Treat chronic infection

Treat chronic inflammation

Treat cholestasis

Treat fibrosis

Treat copper accumulation

Treat GI side effects

Manage hepatic encephalopathy

Manage ascites

DDx Acute Liver Failure

Hepatotoxins

Septicemia

Pancreatitis

Infectious Canine Hepatitis (CAV)

Hypoxia/Ischemia

Exacerbation of Chronic Liver Dz

SIRS

DDx Icterus

Pre-Hepatic – Hemolysis

Hepatic

Post-HepaticPancreatitis

Pancreatic Neoplasia, Abscess, or Granuloma

Liver, Bile Duct, Duodenal Neoplasia, Abscess or Granuloma

Biliary Mucoceole

Cholecystitis

Cholelithiasis

Duodeonal foreign body

PSS and steroid hepatopathy dogs are almost never icteric

DDx Acute Liver Failure

Hepatotoxins• Acetominophen• Aflatoxins• Anabolic Steroids• Anticonvulsants• Antineoplastics• Arsenicals• Carprofen• Diazapem• Diethylcarbamazine• Griseofulvin

• Itraconazole• Kava Kava• Ketoconazole• Oxabendazole• Mebendazole• Mitotane• Mushrooms• Sago Palm (seeds)• Sulfonamides• Thiabendazole• TMPS

Hepatic Encephalopathy

Abnormal mental status in patients with severe hepatic insufficiency

• Severity of HE does not always correlate with severity of liver disease

• Things that can precipitate an HE episode:– Increased protein intake, GI hemorrhage– Dehydration, diuretic therapy– Barbiturates and other sedatives– Uremia– Infection, endoctoxemia, constipation, increased aneaerobes in

the colon– Increased methionine intake

Progression ofHepatic Encephalopathy

• Mildest form – anorexia and lethargy• May progress to weight loss• Ataxia• Confusion, stupor, loss of training• Pacing and wandering• Twitching progressing to seizures• Vomiting, diarrhea• Temporary blindness• Dementia, seizures, coma• Multifocal deficits on neurologic exam

Tx Acute Liver Failure

Correct fluid an electrolyte imbalances

Treat Coagulopathy

Treat hypoglycemia

Treat hepatic encephalopathy

Control GI hemorrhage

Treat Sepsis if present

Sebastian• 9 year old neutered male pit bull• 2 year history of lower cervical disc disease

• Several episodes of pain and CP deficits• Responded to treatment with prednisone and cage

rest

• 1 week ago ataxia and falling, and vocalizing every time he moves

• The morning after a fight with another dog• Tx prednisone, methocarbamol, Tramadol, cage

rest – no response for 4 days• Sedated for radiographs

Sebastian• 4 days ago Sedated for radiographs

• mid-abdomen 8cm soft tissue mass• no significant enlargement of liver, spleen, R kidney• Cervical & lumbar intervertebral disc calcification• vomited large amount of fluid with coffee grounds

after sedation• Tx carafate, IV fluids, metronidazole, amoxicillin• Albumin 2.1 g/dl (2.2 g/dl low normal)• SAP 2119 U/L• ALT 1434 U/L• Bili 8.2 mg/dl• HCT 30.8%

Sebastian• Referred for ultrasound today• Exam

• Can not walk• Muscle tremors and very jumpy when touched• Icteric skin• Abdomen tense and difficult to palpate• Very large urinary bladder• Scleral injection – owner says had been present for

30 days

Sebastian• Neuro Exam

• Unable to walk, unable to assess postural reflexes and CP

• Cranial nerves normal• Spastic paresis in all 4 limbs (UMN reflexes)• Conscious motor activity in all 4 limbs• Lower cervical pain• Dx - Lower cervical spinal cord disease

• Catheterized bladder and removed 1.5L of orange urine (bilirubin crystals)

• Hx – has been on clomipramine for some time, for anxiety

SebastianProblem List• Cervical myelopathy and tetraparesis

• Surgery not an option for these owners

• Icterus – likely hepatic, post-hepatic and hemolysis can not be ruled out

• Hematemesis – prednisone, liver failure, spinal cord injury

• Twitching – hepatic encephalopathy, metronidazole toxicity, serotonin syndrome

• Mid abdominal mass• Mild anemia

Sebastian

Sebastian

Sebastian

SebastianRadiographs• Large amount of air in the stomach• Gastric axis shifted cranially

Normal DogRadiographs• Large amount of air in the stomach• Gastric axis shifted cranially

SebastianRadiographs• Large amount of air in the stomach• Gastric axis shifted cranially

SebastianRadiographs• Large amount of air in the stomach• Gastric axis shifted cranially• Intestines appear distended with fluid• No mid abdominal mass seen• Increased soft tissue density in right cranial abdomen• Cervical and lumbar spondylosis• Cervical and lumbar mineralized disc material• Disc material in the spinal foramina• Dx – microhepatia• Dx – degenerative disc disease

SebastianAbdominal Ultrasound• Difficult because of the great amount of air in

the stomach, due to aerophagia• Small areas of the liver seen, hyperechoic,

mottled in echotexture• Gall bladder not seen• Many fluid filled loops of bowel

PT, PTT - normal

SebastianPlan• Discontinue prednisone, Tramadol, clomipramine,

metronidazole• Continue Carafate, IV fluids (LRS + 20 mEq/L KCl),

ampicillin IV• add milk thistle, famotidine• Fast overnight and repeat ultrasound tomorrow• Repeat CBC, panel, lytes tomorrow• Send out Lepto titers• Express bladder or catheterize to empty bladder TID

SebastianDay 2• Ate chicken and drank water yesterday• Twitching stopped• Skin appears less icteric, scleral injection improved• HCT 17.7%, Hb 5.6 g/dl• Albumin 1.6 g/dl• Bili 5.4 mg/dl• Neutrophilia 20K/ul• Lytes normal• No vomiting, no melena• Urine is golden, not orange• Eating chicken and drinking

SebastianUltrasound• Liver small, mottled, hyperechoic• Liver cytology – suppurative hepatitis with cholestasis• Gall bladder wall thickened - cholecystitis• No fluid in the abdominal cavity

Plan – add Baytril & Vitamin K, monitor PCV

SebastianDay 3• Vomited overnight – chicken, melena on thermometer• HCT 14.9%, Hb 4.6%• neutrophils 21.7K/ul• Albumin 1.5 g/dl• Lytes normal

Plan• Whole blood transfusion• Ate chicken & rice well that night, drinking water• Continue milk thistle, ampicillin, enrofloxacin, carafate,

famotidine, Vit K, IV fluids, catheterize TID

SebastianDay 4• Not feeling well, passed melena, fever 103.4F• Will not eat, licked lips when food offered• Abd US – still no evidence of perforation, but deep

ulcer seen in the duodenum• PCV 25%, albumin 1.8 g/dl, lytes normal

Plan• Continue milk thistle, ampicillin, enrofloxacin, carafate,

famotidine, Vit K, IV fluids, catheterize TID

SebastianDay 5• Fever has resolved, feels better• Eating chicken, but not rice• Urinating on own, but does not empty the bladder• Can support weight on rear legs but not front legs• If ulcer perforates, owners will not do surgery• PCV 20%, albumin 1.8 g/dl

Plan• Continue milk thistle, ampicillin, enrofloxacin, carafate,

famotidine, Vit K, IV fluids, catheterize BID

SebastianDay 6• Will not eat, no fever• When put on feet, attempts to move forward, but can

not move front legs well yet, can take a few steps• Urinating on own• neutrophils 75K, monocytes 1,100/ul• No stools passed, but melena on thermometer

Ultrasound

SebastianDay 6• Will not eat, no fever• When put on feet, attempts to move forward, but can

not move front legs well yet, can take a few steps• Urinating on own• neutrophils 75K, monocytes 1,100/ul• No stools passed, but melena on thermometer

Ultrasound

SebastianDay 6• Will not eat, no fever• When put on feet, attempts to move forward, but can

not move front legs well yet, can take a few steps• Urinating on own• neutrophils 75K, monocytes 1,100/ul, 6% bands• No stools passed, but melena on thermometer

Ultrasound• Local peritonitis R Cranial abdomen

SebastianPlan• Drained fluid percutaneously• Discontinue catheterization• Continue milk thistle, ampicillin, enrofloxacin, carafate,

famotidine, Vit K, IV fluids• Wrap front feet to prevent abrasions from knuckling

SebastianDay 7• neutrophils 38K, monocytes normal, 3% bands• HCT 20%• Albumin 1.6 g/dl, glob 5.3 g/dl• SAP >4600 U/L, ALT 1868, bili 6.7 mg/dl• Black tarry liquid stools

Plan• Barium 5ml/lb PO• Continue milk thistle, ampicillin, enrofloxacin, carafate,

famotidine, Vit K, IV fluids, wrap front feet

Sebastian

Sebastian

Sebastian

SebastianDay 8• Owners came to visit – Sebastian ate a rib eye• Black tarry soft stools• Can walk 5-10 feet without assistance

Plan• Continue milk thistle, ampicillin, enrofloxacin, carafate,

famotidine, Vit K, IV fluids, wrap front feet

SebastianOver the next 2 weeks• Switched form injectable to oral meds• Recovered well

Recurrence of liver failure 1 year later• Owners elected euthanasia

Inky

Inky

Handouts• This PowerPoint – behind the blue tab• Client Drug Handouts

• Colchicine• Cyproheptadine• Lactulose• Milk Thistle• SAMe• Ursodiol

Handouts• Client Handouts

• Cholangiohepatitis• Chronic Liver Disease• Fatty Liver• Leptospirosis• Portasystemic Shunt