Liver Document - Treatments

What are the main reasons to use glucocorticoids in hepatobiliary disease?

Anti-inflammatory, anti-fibrotic, cholerectic effects, appetite stimulation, and reduction of copper absorption.

In which diseases are glucocorticoids indicated?

Chronic hepatitis, cholangitis, or cholangiohepatitis with lymphoplasmacytic inflammation.

Why are glucocorticoids contraindicated in infectious hepatitis?

They suppress immunity, allowing infection to worsen.

Why are glucocorticoids not recommended for acute hepatitis?

They have been linked to increased mortality; most acute liver injuries recover with supportive therapy alone.

What complication can glucocorticoids cause in dogs with portal hypertension?

Exacerbation of GI ulceration and worsening of portal hypertension.

What are the potential metabolic side effects of glucocorticoids?

Muscle catabolism, weakness, polyuria/polydipsia, immunosuppression.

Why is prednisolone preferred over prednisone in cats?

Cats have limited hepatic ability to convert prednisone to prednisolone.

What is the typical prednisolone dose for chronic hepatitis in dogs?

1–2.2 mg/kg/day (max 60 mg/day), tapered after improvement.

Which glucocorticoid offers more localized hepatic action and fewer systemic effects?

Budesonide — undergoes extensive first-pass hepatic metabolism.

What is a key precaution when using budesonide?

 It can still suppress the HPA axis despite lower systemic absorption.

What are alternatives to glucocorticoids in chronic hepatitis or steroid-refractory cases?

Azathioprine, mycophenolate mofetil, cyclosporine, chlorambucil, and leflunomide.

Which drug is preferred for chronic hepatitis in dogs with immune-mediated etiology?

Cyclosporine (≈50% remission rate).

Why is azathioprine generally avoided in cats?

Causes severe bone marrow suppression.

Which immunosuppressant can cause hepatotoxicity in dogs?

Azathioprine.

What are common adverse effects across immunosuppressants?

GI upset, hepatotoxicity, pancreatitis, and bone marrow suppression.

What monitoring is recommended during immunosuppressive therapy?

Periodic CBC, liver enzymes, and drug level monitoring (especially cyclosporine).

What is the mechanism of ursodeoxycholic acid (ursodiol)?

Hydrophilic bile acid that replaces toxic hydrophobic bile acids, stimulates bile flow, and protects hepatocytes.

What are other benefits of ursodiol?

Anti-apoptotic, antioxidant, and membrane-stabilizing effects.

What is the dose of ursodiol?

15 mg/kg/day, divided (BID dosing preferred for steady flow).

Why should ursodiol be given with food?

It’s fat-soluble, enhancing absorption.

When is ursodiol contraindicated?

Biliary obstruction, since increased bile flow can cause rupture.

Which antioxidant may have mild cholerectic properties?

SAMe, via increased glutathione synthesis.

What is the mechanism of colchicine in liver disease?

Inhibits microtubule assembly, increasing collagenase activity and decreasing fibrosis.

When is colchicine used?

For chronic fibrotic liver disease or amyloidosis.

What is the main adverse effect of colchicine?

Gastrointestinal upset (vomiting, diarrhea).

What is the typical dose of colchicine for dogs?

0.03 mg/kg/day.

True or False? There is little evidence of the efficacy of colchicine.

True.

What are other drugs that may have mild anti-fibrotic effects?

Glucocorticoids, SAMe, silymarin, vitamin E, azathioprine, zinc, penicillamine, and possibly losartan (angiotensin blocker).

Name common antioxidants used in hepatobiliary disease

Vitamin E, SAMe, silymarin/silybin, zinc, curcumin, NAC, and ursodiol.

What is the general role of antioxidants in hepatic therapy?

Reduce oxidative injury, stabilize membranes, and support hepatocellular regeneration.

What is the role of vitamin E?

Protects against lipid peroxidation in membranes; water-soluble forms are better in cholestatic disease.

Vitamin E dose for dogs?

10 IU/kg/day (as d-alpha tocopherol).

What is SAMe (S-adenosyl-L-methionine)?

A methyl donor and precursor of cysteine/glutathione for detoxification and antioxidation.

What happens to SAMe levels in liver disease?

Decrease due to reduced synthesis and SAMe-synthase activity.

SAMe dose for dogs?

20 mg/kg/day.

What are the veterinary SAMe formulations?

Denosyl® (SAMe alone), Denamarin® (SAMe + silybin), and Marin® (silybin + vitamin E + zinc).

What is silymarin/silybin, and what is its role?

Extract from milk thistle; increases superoxide dismutase, protects against oxidative and toxin-induced hepatic injury.

What is the typical silybin dose?

5 mg/kg (50–250 mg BID).

What toxicities has silybin been shown to protect against?

Acetaminophen and Amanita mushroom poisoning.

What is N-acetylcysteine (NAC) used for?

Replenishes glutathione, improves hepatic blood flow, and protects against ischemia-reperfusion injury.

How can NAC be administered?

IV (140 mg/kg loading, then 50–70 mg/kg × 7 doses) or PO (50–70 mg/kg TID).

When is NAC especially useful?

In hospitalized patients with acute hepatopathies unable to take oral meds.

True or False? Anti-oxidants such as vitamin E, s-adenyl-L-methione (SAMe), silymarin/silybin, zinc, curcumin, N-acetylcysteine and UDA has lots of peer-reviewed evidence to support its treatment of naturally occurring liver disease in dogs and cats.

False. There is little peer-reviewed evidence to support the use of antioxidants to treat naturally occurring liver disease in dogs and cats.

When are copper chelators indicated?

When hepatic copper > 1000 ppm (toxic accumulation).

What is the first-line chelator for copper-associated hepatitis?

D-penicillamine

What is the D-penicillamine dose?

10–15 mg/kg BID with meals.

What is the mechanism of copper chelators?

Bind extracellular copper → increase urinary excretion → draw intracellular copper outward.

What are side effects of D-penicillamine?

Vomiting, anorexia, and reactions similar to penicillin hypersensitivity.

What other chelators exist but are less available?

2,2,2-tetramine and tetrathiomolybdate.

What mineral supplement reduces copper absorption?

 Zinc (zinc gluconate or acetate).

How does zinc reduce copper absorption?

Induces intestinal metallothionein, which binds and sequesters copper in enterocytes.

When should zinc be given relative to food?

1 hour before meals (food reduces absorption).

Why should chelators and zinc not be given together?

Chelators bind zinc, reducing efficacy of both.

How long is chelation therapy given for?

3–8 months depending on copper level:
- Mild (1,000–1,500 ppm): 3–4 mo
- Moderate (1,500–2,500 ppm): 4–6 mo
- Severe (> 3,000 ppm): 6–8 mo.

What follow-up is recommended after chelation?

Recheck liver enzymes or repeat biopsy for copper quantification.

When copper levels normalize, what maintenance is used?

Low-copper diet ± low-dose chelator or zinc supplement.

What is the goal of diet therapy in HE, hepatic encephalopathy?

Reduce ammonia production while maintaining adequate protein for repair.

What protein level is recommended for dogs without HE?

~60 g/1000 kcal (normal hepatic diet).

What protein level for dogs with HE?

45–50 g/1000 kcal (reduced protein).

What protein sources are preferred in HE diets?

Eggs, dairy, and soy (less ammoniagenic).

What is the main pharmacologic agent for HE?

Lactulose (reduces intestinal ammonia absorption).

What is the oral dose of lactulose?

0.25 mL/kg PO 2–3 × daily; adjust to produce soft stools.

What is the IV or enema form of lactulose used for?

Moribund or comatose patients unable to take oral medication.

What antibiotics can reduce ammonia-producing bacteria?

Metronidazole, ampicillin, or neomycin (though metronidazole is most common).

What is a recent recommendation regarding chronic antibiotics for HE?

Not always necessary; lactulose + diet may suffice.

Why is hydration critical in HE?

Prevents ammonia concentration buildup and renal hypoperfusion.

What dietary modification helps manage ascites from PH, portal hypertension?

Sodium restriction (low-sodium liver diets).

What is the preferred diuretic for chronic ascites in PH?

Spironolactone (aldosterone receptor antagonist).

When might a loop diuretic (furosemide) be added?

In acute exacerbations, alongside spironolactone, then tapered off.

Why is spironolactone preferred over furosemide long-term?

It spares potassium and reduces RAAS activation.

What can worsen PH and HE if fluid is removed too aggressively?

RAAS activation → sodium retention → worsening ascites and hypokalemia.

What is the role of IV fluids in PH management?

Correct dehydration, improve renal perfusion, and reduce RAAS drive.

Why are dogs and cats with portal hypertension predisposed to ulcers?

Gut ischemia from venous congestion.

Why is sucralfate (Carafate) often ineffective for proximal GI ulcers in these patients?

It acts locally and poorly adheres to mucosa under bile conditions.

Which acid suppressant is preferred?

Omeprazole (proton pump inhibitor).

What is a risk of long-term PPI use?

Alters gut microbiota and may worsen HE.

Why should PPIs be tapered slowly when discontinued?

To avoid rebound hypergastrinemia and acid rebound.

What other GI drugs can support hepatic patients?

Antiemetics such as serotonin inhibitors (ondansetron) or NK-1 antagonists (maropitant).

Drugs to use for inflammatory hepatitis:

Immunosuppression ± glucocorticoid.

Drugs to use for cholestatic disease:

Ursodiol, SAMe, antioxidants.

Drugs to use for fibrosis:

Colchicine, anti-fibrotics, antioxidants.

Drugs to use for copper storage disease:

Chelators, zinc, low-copper diet.

Drugs to use for encephalopathy:

Lactulose, protein-modified diet, metronidazole.

Drugs to use for portal hypertension

Spironolactone, sodium restriction.