Liver Failure

Introduction

Liver failure results from inadequate liver function. It occurs even though the liver has a large functional reserve and a high regenerative capacity. Due to the multiple functions of the liver the animal may present with a variety of clinical signs and although some syndromes such as GI ulceration and jaundice are very suggestive of hepatic disease, often ancillary tests are necessary to diagnose liver failure.

Causes

Hereditory Liver Disease

Portsosystemic vascular abnormalities such as portosystemic shunt (PSS) and storage diseases.

Low Liver Mass

A low liver mass depletes the functional reserve.

NB: liver enzyme levels in blood may not be markedly raised in chronic ongoing liver damage because there may be few liver cells remaining to leak enyzmes

Remodelling of the Vascular and Connective Components after Damage

This may lead to inadequate nutritional supply to the hepatocytes, thus reducing their function

Impaired Function of One Specific/Many of its Diverse Functions

The livers many functions include detoxification and inactivation of drugs and hormones; carbohydrate metabolism; lipid metabolism and storage; biotransformation and excretion; immunological function; vitamin storage, activation and elimination; and the storage of minerals. Failure of one or more of these functions can result in disease.

Signalment

Several breed predispositions exist. These include hereditory abnormalities such as PSS and storage diseases, amyloidosis and idiopathic chronic inflammatory hepatobiliary disease. Otherwise there may be a history of the ingestion of hepatotoxic drugs which raises suspicion of disease.

Clinical Signs

The animal may present with non specific signs such as weight loss, anorexia, vomiting, diarrhoea, lethargy and PU/PD. As these signs may occur in many disease processes, clinical pathology may be necessary to confirm liver disease. The may also present with syndromes specifically related to primary or secondary liver disease such as:

• Icterus

• Photosensitisation

• Hepatic Encephalopathy

• Bleeding Tendencies or coagulopathy

• Hypoalbuminaemia and ascites

• Hepatomegaly or fibrosis of the liver

• Drug intolerance

These specific signs are more likely to occur further into the disease course as the liver has an extremely large functional reserve.

Diagnosis

Laboratory Tests

• Haematology, biochemistry, urinanalysis
• Serum bile acid test pre- and post-prandial
• Coagulation profile

• Plasma ammonia
• Abdominocentesis

Imaging

Radiography can be used to assess the size and shape of the liver. Diffuse hepatomegaly is suggestive of infiltrative disease (such as neolasia or amyloidosis), inflammation, and congestion. Focal hepatomegaly is more suggestive of a single neoplastic mass, cyst , abscess, regenerative nodule or granuloma. Hepatomegaly or a small liver may be suggestive of acute or chronic disease. Reduced liver size suggests fibrosis and atrophy. The use of radiographic contrast studies can be used to identify vascular abnormalities such as PSS.

Ultrasonography is a useful tool for assessing the liver for signs of disease. It can be used to evaluate the parenchyma, vascular system and biliary system for pathology but is not the most reliable tool for assessing liver size. Diffuse disease can be identified and further classified as hypoechoic or hyperechoic. Hypoechoic pathology includes hepatic lymphoma, congestion and suppurative disease. causes of hyperechoic liver arenchyma include fibrosis (accompanied by regenerative nodules, ascites and a small size), neoplasia, lipidosis and corticosteroid hepatopathy. With localised disease as focal lesion should be identifed, and ultrasonograhic appearance may allow the differentiation of cysts, regenerative nodules, abscesses, neoplasia, granulomas and haematomas, however this is not always possible due to their sometimes variable appearance. If disease is diffuse or a localised mass is ameanable to biopsy then ultrasound can be used to guide sampling. It is also extremely useful for the diagnosis of vascular abnormalites and biliary stasis.

Biopsy

Livers with either diffuse disease or a focal lesion that is ameanable to biopsy should be biospied and the sample sent for histopathology if diagnosis has not yet been achieved.

Either a surgical biopsy or ultrasound guided needle biopsy should be performed to confirm diagnosis. However coagulation test should be performed before any biopsies are taken as the liver is a very vascular organ and animals with liver disease are often deficient in clotting factors (which results in a coagulopathy). Clearly there are risks associated with the procedure and the risk-benefit should be considered before performing a biopsy.

Treatment

The aim of treatment are to:

• Remove the causative agent
• Stop inflammation
• Minimise fibrosis
• Promote regeneration
• Treat secondary complications such a ascites, secondary bacterial infection and hepatic encephalopathy.

There are numerous drugs including glucocorticoids, immunosuppressive agents, vitamins, antioxidants, bile acids (ursodeoxyycholic acid (UDCA)), antioxidants such as S-Adenosyl-L-methionine (SAMe), vitamin C and E and milk thistle (silymarin), and antifibrotic drugs. Treatment of liver-specific syndromes such as photosensitisation and hepatic encephalopathy are cover in their associated sections.

References

Rutgers, C (1996) Liver disease in dogs In Practice 1996 18: 433-44

Rutgers, C (1996) Feline liver disease' In Practice 1998 20: 16-2

Dunn, j (1992) Assessment of liver damage and function In Practice 1992 14: 193-200

Bexfield, N & Watson, P (2006) Diagnosis of canine liver disease In Practice 2006 28: 444-45

1) Failure of detoxification

Aldosterone - a failure of its proper inactivation results in hypervolaemia since a feature of this hormone is to cause sodium and hence water rentention. This is a factor in the development of ascites

Oestrogen - a failure of its proper inactivation will result in an accumulation of this hormone with atrophy of the genitals and an enlargement of the breasts in the male

Plant Pigments - failure to detoxify will lead to their accumulation in the tissues and photosenistisation may result if they are photodynamic

2) Metabolic upset

• The failing liver is unable to convert ammonia to urea, resulting in a rise in the level of blood ammonia
• Lowered level of plasma albumin contributes to the development of ascites

3) Failure of