Liver Document - Liver diseases

Chronic hepatitis, copper-associated hepatitis (CAH), acute hepatitis (AH), granulomatous hepatitis, cholestatic liver disease, cirrhosis/end-stage liver disease, hepatic lipidosis

Define chronic hepatitis.

A chronic inflammatory disease of the liver characterized by hepatocellular necrosis, inflammation, and fibrosis.

What is the typical histologic triad of chronic hepatitis?

Inflammation (lymphoplasmacytic), hepatocellular necrosis/apoptosis, and fibrosis.

What species is most commonly affected by chronic hepatitis?

Dogs (especially middle-aged to older), rarely cats.

What are the most common causes of chronic hepatitis in dogs?

Idiopathic (immune-mediated), copper accumulation, drug-induced, infectious (rare), or secondary to toxins.

What breeds are predisposed to idiopathic chronic hepatitis?

Dobermans, Cocker Spaniels, Labradors, Dalmatians, Bedlington Terriers, Skye Terriers, West Highland White Terriers.

What are typical clinical signs of chronic hepatitis?

Lethargy, anorexia, vomiting, weight loss, polyuria/polydipsia, ascites, and intermittent jaundice.

What are laboratory findings in chronic hepatitis?

Increased ALT (early), increased ALP and GGT, mild to moderate hyperbilirubinemia, low albumin (late), prolonged PT/PTT.

What may the bile acids test reveal?

Markedly elevated pre- and post-prandial bile acids due to decreased clearance and shunting.

What imaging findings suggest chronic hepatitis?

Microhepatica, irregular margins, hyperechoic parenchyma, and acquired shunts.

What histopathologic features confirm CH?

Mononuclear portal inflammation, interface hepatitis, necrosis, regenerative nodules, bridging fibrosis.

What is interface hepatitis?

Lymphocytic infiltration at the junction between portal tracts and parenchyma, leading to hepatocyte apoptosis.

What are the goals of treatment for CH?

Reduce inflammation, control fibrosis, treat copper accumulation if present, and support hepatic regeneration.

What is the first-line treatment for idiopathic CH?

Immunosuppression with prednisolone or budesonide, plus ursodiol, SAMe, and vitamin E.

What additional immunosuppressants can be added?

Cyclosporine or azathioprine (dogs only).

When copper accumulation is present, what should be added?

D-penicillamine or zinc.

What is the prognosis for chronic hepatitis?

Variable; fair to good if caught before cirrhosis, poor if advanced with ascites or encephalopathy.

In chronic hepatitis → __ dominantes early, __ later and __ rises with progression.

ALT, ALP, bilirubin

What causes copper-associated hepatitis?

Abnormal hepatic copper accumulation causing oxidative injury, inflammation, and necrosis.

What are two major forms of CAH?

Primary (genetic) defect in copper excretion and secondary (acquired) accumulation from cholestasis.

Which breeds have hereditary CAH?

Bedlington Terriers (COMMD1 mutation), Labrador Retrievers, Dobermans, and West Highland White Terriers.

What does the COMMD1 gene normally do?

Regulates biliary copper excretion — its loss causes hepatic copper buildup.

What copper concentrations are diagnostic for CAH?

> 1,000 ppm dry weight (normal < 400 ppm).

Where in the lobule does copper accumulate in primary CAH?

Centrilobular (zone 3) hepatocytes.

Where does copper accumulate in secondary CAH (cholestasis)?

Periportal (zone 1) hepatocytes.

What are the clinical signs of CAH?

Similar to CH — chronic liver enzyme elevation, lethargy, anorexia, jaundice, and sometimes acute collapse.

What is the primary diagnostic test for CAH?

Liver biopsy with rhodanine or rubeanic acid stain and quantitative copper analysis.

What are the treatment options for CAH?

Copper chelation (D-penicillamine or trientine), zinc therapy, low-copper diet, antioxidants, and ursodiol.

What diet modifications are recommended for CAH?

Avoid liver, shellfish, nuts, chocolate; feed prescription low-copper hepatic diets (e.g., Royal Canin Hepatic, Hill’s l/d).

What is the duration of chelation therapy for CAH?

3–8 months depending on copper level, then maintenance with zinc or diet alone.

What is the long-term prognosis for CAH?

Good with early detection and lifelong copper control.

How are primary CAH and secodnary CAH different and similar?

Primary CAH: genetic, centrilobular

Secondary CAH: cholestatic, periportal

Both → oxidative injury → chronic hepatitis

Define acute hepatitis.

Rapid hepatocellular necrosis and inflammation secondary to toxins, hypoxia, or infection.

What are common causes of AH in dogs and cats?

Drugs/toxins (NSAIDs, phenobarbital, carprofen, acetaminophen), infection (leptospirosis, adenovirus, herpesvirus), and hypoxia.

What are the clinical signs of acute hepatitis?

Sudden vomiting, anorexia, lethargy, jaundice, and possibly coagulopathy.

What are key lab findings in AH?

Marked ALT and AST elevation, mild ALP/GGT increase, hyperbilirubinemia, possible hypoglycemia.

What does imaging usually show?

Enlarged, hypoechoic liver.

What is the mainstay of AH treatment?

Aggressive supportive care: IV fluids, antiemetics, antioxidants (NAC, SAMe), and nutrition.

When should immunosuppressive therapy be avoided?

In acute hepatitis unless clear immune-mediated cause is confirmed.

What specific antidote treats acetaminophen toxicity?

N-acetylcysteine (NAC) IV or PO.

What adjuncts can support hepatic regeneration post-AH?

SAMe, silybin, vitamin E, ursodiol (if no obstruction).

What is the prognosis for AH?

Guarded to good — reversible if cause identified early; poor if fulminant failure or hepatic encephalopathy occurs.

Define granulomatous hepatitis.

Chronic hepatic inflammation dominated by macrophages forming granulomas.

What are common causes of granulomatous hepatitis?

Infectious: Mycobacteria, Bartonella, Leishmania, Histoplasma, Toxoplasma, FIP.
Noninfectious: Idiopathic immune-mediated.

What are the clinical signs of granulomatous hepatitis?

Chronic weight loss, fever, hepatomegaly, and sometimes icterus.

What does cytology of granulomatous hepatitis often reveal?

Macrophages, multinucleated giant cells, organisms (if infectious).

How is granulomatous hepatitis confirmed?

Liver biopsy with special stains (Ziehl–Neelsen, PAS, silver, Fite-Faraco).

What treatment is used for infectious causes of granulomatous hepatitis?

Targeted antimicrobial/antiparasitic therapy based on organism identified.

How are noninfectious (immune-mediated) cases of granulomatous hepatitis treated?

Immunosuppressive therapy (prednisolone ± azathioprine or cyclosporine).

What is the prognosis of granulomatous hepatitis?

Variable — depends on cause and response to therapy.

Define cholestasis.

Impaired bile formation or flow leading to bile acid retention and hepatocellular damage.

Differentiate intrahepatic vs extrahepatic cholestasis.

Intrahepatic: hepatocellular or canalicular dysfunction;

Extrahepatic: bile duct obstruction

What are the hallmark lab findings of cholestatic liver disease?

Increased ALP and GGT (especially in dogs), conjugated hyperbilirubinemia, mild ALT/AST rise.

What are common causes of extrahepatic cholestasis?

Pancreatitis, cholelithiasis, mucocele, neoplasia, duodenal obstruction.

What drugs can cause intrahepatic cholestasis?

Anabolic steroids, azathioprine, chlorpromazine.

What imaging findings indicate cholestasis?

Dilated bile ducts, thickened gallbladder wall, or mucocele pattern.

What are treatments for cholestasis?

Ursodiol (if non-obstructive), antioxidants, low-fat diet, and addressing the underlying cause.

When is surgery indicated for cholestatic liver disease?

In extrahepatic obstruction or gallbladder rupture.

Intrahepatic cholestasis can be medically managed

Define cirrhosis.

End-stage hepatic fibrosis with nodular regeneration and distorted architecture.

What are typical sequelae of cirrhosis?

Portal hypertension, acquired shunts, ascites, and hepatic encephalopathy.

What are clinical features of cirrhosis and end-stage liver?

Weight loss, ascites, stunted growth, icterus, and intermittent neurologic signs.

What lab findings occur in cirrhosis?

Normal or mildly elevated liver enzymes, low albumin, high bilirubin, prolonged PT/PTT.

Why may ALT normalize in advanced cirrhosis?

Few hepatocytes remain functional, reducing enzyme release.

What imaging findings are characteristic?

Small nodular liver, irregular margins, large spleen, and ascites.

What is the treatment goal in cirrhosis?

Symptomatic management — diuretics, low-sodium diet, antioxidants, lactulose, and supportive care.

What is the prognosis of cirrhosis?

Poor; irreversible once fibrosis and portal hypertension are advanced.

What is feline hepatic lipidosis?

Accumulation of triglycerides in hepatocytes causing hepatic failure, often secondary to anorexia or stress.

What cats are predisposed to hepatic lipidosis?

Overweight adult cats under stress or with concurrent disease.

What are the hallmark lab findings of hepatic lipidosis?

Severe ALP elevation (>> GGT), hyperbilirubinemia, mild ALT increase.

What is essential for treatment of hepatic lipidosis?

Aggressive nutritional support via feeding tube, fluids, antiemetics, antioxidants.

Why is protein restriction avoided in hepatic lipidosis?

Cats require high protein for hepatic repair; restriction worsens recovery.

What is the prognosis for hepatic lipidosis?

Good if feeding initiated early and maintained until normal intake resumes.

What other feline liver diseases are common?

Cholangitis/cholangiohepatitis, FIP, lymphoma, hepatic lipidosis.