Ursodiol

Liver Disease Ursodiol as one therapeutic option

The liver is a multifaceted organ. It is involved in digestion by the metabolism of protein, lipids and carbohydrates; storage of vitamins, minerals and production of bile acid, which is essential for detoxification of many end-products of digestion. It also produces and stores coagulation factors recruited for production of clots resulting in wound healing. This organ protects itself by regenerating his own cells to a certain extend, but can still be at great risk due to its filtering capacity and exposure to many metabolites, products of digestion, drugs, and toxins. This could be leaving temporary or even permanent damage to the cells it harbors.

Symptoms or clinical signs you might encounter in animals with liver disease are vomiting, anorexia, gastric ulcers, diarrhea, liver encephalopathy, fever, abnormal coagulation, fluid in abdomen (ascites), yellow gums, areas of skin and/or eyes (jaundice), weight loss, increase water consumption and excessive urination. There is a wide repertoire of clinical signs. Of those, the ones that are more characteristics of primary liver disease are ascites, jaundice and liver encephalopathy*. But, a combination of signs can occur, especially if there are secondary diseases. Making imperative a good thru history of current medications with doses, ingestion of new foods or treats, history of toxicities, vaccine records, exposure to outdoor areas and/or chronic health issues.

Laboratory findings in a chemistry panel usually show elevations of liver enzymes like ALT, ALP, AST, and/or GGT. The degree in severity in each laboratory parameter of liver enzymes can give us clues of where in the liver is the problem is located. These, in combination, with a specific clinical sign and other blood values like white blood cell count, platelet count, BUN, cholesterol and total protein can guide us towards a diagnosis. We may need the help of other blood diagnostics and imaging like abdominal X-rays to evaluate liver size and ultrasound to see if diffuse disease is present. During ultrasound, is possible to take liver samples using fine needle aspirate of the area of concern for cytology interpretation and complete diagnosis.

Treatment is initiated according to the type of liver disease: primary liver disease (see Table 1) versus by secondary causes like some endocrine diseases (Cushing’s disease, diabetes mellitus), hepatic lipidosis or “fatty liver” from malnutrition (eg. in cats), tumors in the surroundings (extra-hepatic tumors), infections (viral, bacterial, fungal), pancreatitis and others. Attention is given to electrolyte, acid-base balance, and proper nutrition to give the best possible regeneration of the cells and decrease the liver workload during digestion.

Now, when there are cases involving intrahepatic cholestasis** and biliary obstruction has been ruled out using tests like ultrasound, we can rely on medications like Ursodiol (Ursodeoxycholic acid). Ursodiol (Trade Name: Actigall) is a naturally occurring, water soluble bile acid, that stimulates the flow of bile and protect the liver from developing an obstruction. It is mainly used to treat primary biliary cirrhosis, cholestatic liver disorders and chronic liver disease. Since Ursodiol is given orally as a capsule in humans, your veterinarian may prescribe a compounded formulation to achieve the right dose. Dogs and cats usually receive the medication orally with a fatty meal twice daily. Horses DO NOT possess a gall bladder so bile is not produced for which this drug will be of no benefit. Guinea pigs and rabbits should NOT receive it since they are hindgut fermentors and do convert the compound into a toxic substance. A side effect in all animals includes diarrhea. Typical dosage goes from 10 to 15 mg/kg once daily to twice daily depending on severity. The medication should be stored in light resistant and tight containers at room temperature. If is in liquid form, it should be shaken well and discarded after 35 days.

Notes:

*Liver encephalopathy occurs when ammonia, productions of metabolism or neurotoxins are not cleared by the liver causing damage to neuron in the brain. Symptoms are circling, head pressing, weakness, ataxia, blindness, seizure and even coma.

**Cholestasis means impairment of the release of bile from liver cells at the location before reaching biliary ducts.

Table 1: Examples of primary and secondary liver disease

 

PrimarySecondaryGall Bladder and Extrabiliary system
Portosystemic Shunts Hepatotoxins (NSAID, aflatoxins, blue-green algae) Obstructive-Pancreatitis
Canine Chronic Hepatitis
-Copper accumulation
-Idiopathic 
-Lobular Dissecting
Infectious
-Viral (Adenovirus)
-Leptospirosis
-Sepsis
- Toxoplasmosis
-Fungal
Cholecystitis
Hepatic cysts and Nodular hyperplasia Hepatic Lipidosis due to 
-Malnutrition
-Stress 
-Diabetes mellitus
-Inflammatory bowel disease 
-Pancreatitis
-Cholangiohepatitis
Choleliths
Hepatic Neoplasia
-Primary tumors
-Metastatic Tumors
-Lymphoma
Metabolic Effects
-Diabetes Mellitus
-Hyperthyroidism
-Cushing’s disease
Parasitic Infection
Miscellaneous disease
-Glycogen Storage Disease
-Hepatic Amyloidosis
-Liver Fibrosis
Hepatocutaneous Syndrome
-Pancreatic tumor 
-Neuroendocrine tumor
Gall bladder rupture

 

REFERENCES:

(1) Kahn, C. M., & Line, S. (9th Ed.). (2005). The Merck/Merial Manual For Pet. In Chapter: Hepatic disease in small animals. Pages 368-389. Simon and Schuster.

(2) M. G. Papich (2011). Saunders Handbook of Veterinary Drugs: Small and Large Animal. 3rd Edition. Elsevier Saunders. Pages 795-796.

Brief biography:

Dr. Joanne Fernandez-Lopez is a small animal veterinarian graduated from North Carolina State University in 2014. She has been working at a small animal general practice in the South Miami Area. Recently, she accepted a position at a Small Animal Internal Medicine and Surgical internship in west Florida to pursue specialization. Her interest are dermatology, surgery, emergency medicine, exotic animal medicine, marine biology and research.



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