Cholestatic liver diseases in dogs & cats and treatment

The Concept Of Cholestasis 

Cholestasis refers to a pathological state in which bile formation, secretion, and excretion are impaired due to various reasons inside and outside the liver, and bile cannot flow into the duodenum normally for metabolism. Cholestasis liver disease is a general term for hepatobiliary diseases whose main manifestations are cholestasis caused by various reasons. There are many causes of cholestatic liver disease, including viruses, bacteria, parasites, drugs, poisons, autoimmunity, stones, tumors, genetic diseases, etc.

Due to poor bile excretion, the biochemical indicators of the bile duct system ALKP and GGT, the bilirubin indicator TBIL, and the serum total bile acid indicator TBA may all increase. If there is further liver damage, liver enzyme indexes AST and ALT indexes may also increase.

Etiological Classification Of Common Cholestatic Diseases In Dogs And Cats

Cholesterol precipitation: the most common type of cholestasis disease

A high proportion of cholesterol in the bile or the low proportion of bile acid and lecithin in the bile will leads to cholesterol precipitation, which is deposited in the biliary system, causing cholestasis and severe stones that can form. There are agglomerated flocculent deposits in the gallbladder on imaging examination. Such diseases are generally treated with choleretic drugs to clear the biliary tract.

Protein precipitation: hyperlipidemia and elderly animals are prone to get such diseases

proteinaceous substances in the bile are precipitated, causing a mucous cyst of the gallbladder. There are "kiwi-like" deposits in the gallbladder imaging examination. The pathogenesis is still unclear and generally used the surgical treatment to remove the gallbladder.

Blockage of the biliary tract due to mechanical reasons

Parasites, biliary system tumors, liver tumors, pancreatic tumors, intestinal inflammation, etc. The biliary system is squeezed by the mechanical or external force, resulting in poor bile excretion. Surgery combined with medication is generally used.

The Role Of Bile Acids In The Treatment Of Cholestatic Liver Disease

Hepatoenteric Circulation Of Bile Acid

Bile acid is the final product synthesized by the liver using cholesterol as a raw material. It is called primary bile acid and mainly includes chenodeoxycholic acid (CDCA) and cholic acid (CA). Most of the primary bile acids combine with glycine and taurine to form a combined bile acid, which is secreted from the hepatocytes into the bile duct through the bile salt export pump (BSEP) and enters the duodenum with bile. More than 95% of the bile acids will be reabsorbed in the terminal ileum, enter the hepatic portal vein and return to the liver to participate in a new round of enterohepatic circulation. About 5% of bile acids are excreted in feces.

The Role Of Bile Acids In The Treatment Process

a) Replenish intestinal bile acid, giving bile acid or bile acid derivatives to correct intestinal bile acid deficiency;

b) Increase the bile acid content in the intestine, and inhibit the secretion and synthesis of bile acid in the liver through negative feedback regulation;

c) Activate the bile acid nuclear receptor FXR, thereby up-regulating its target genes and correcting abnormal lipid metabolism;

Ursodeoxycholic acid UDCA has been widely used in the treatment of digestive system diseases. It is approved by the US Food and Drug Administration for gallstone dissolution and primary bile duct PBC. It is now known that UDCA does not activate FXR, but as an antagonist of FXR. Currently, bile acid replacement therapy is mainly used for PBC and cholestasis of pregnancy. UDCA can improve liver function, reduce itching, and increase the time between liver transplantation (or death). It has been reported in the literature that about 40% of patients do not respond to UDCA treatment in PBC. Obeticholic acid (OCA), a new derivative of CDCA, is used as an FXR agonist. When CDCA is administered to PBC patients who are not well treated with UDCA, the effect is significantly improved. As mentioned earlier, FXR activation can reduce fat deposits in the liver and relieve cholestasis in many ways.

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