Practical Gastroenterology Liver Disease Wendy Blount, DVM Primary vs Secondary Liver Disease • One of the most difficult tasks of dealing with liver disease is to distinguish one from another • Primary Liver disease must be treated at it’s cause, if we are to do anything but palliate • Secondary Liver Disease just distracts us from the primary problem, whether liver disease, and/or something else • Secondary Liver Disease = Reactive Hepatopathy • However, as the liver acts as an innocent bystander, it can suffer collateral damage, which we should mediate Primary vs Secondary Liver Disease Signs of Primary Liver Disease – The Liver Is Sick! • Change in liver size or shape – Hepatomegaly – Microhepatia – Liver mass – Irregular liver margins – Radiographs the best test for liver size – Ultrasound the best test for liver shape and to find masses • Icterus without anemia • Hepatic encephalopathy Primary vs Secondary Liver Disease Signs of Primary Liver Disease – The Liver Is Sick! • Acholic feces • Superficial necrolytic hyperkeratosis – aka hepatocutaneous syndrome Primary vs Secondary Liver Disease Signs of Primary Liver Disease • Coagulopathy – The Liver Is Very Sick!! – GI hemorrhage death spiral 1. Increased stomach acidity – Decreased hepatic clearance of gastrin, decreased mucus, mucosal ischemia – Increased bile acids further stimulate HCl secretion 2. Clotting factor’s, AT3 not produced adequately by failing liver – Poor clotting and thromboembolic disease 3. DIC – more AT3 consumption – more thrombosis • Positive Feedback Loop #1 - GI Bleeding exacerbates hepatic encephalopathy • Positive Feedback Loop #2 - Large bleed can cause depletion coagulopathy Primary vs Secondary Liver Disease Signs of Primary Liver Disease • Coagulopathy – The Liver Is Very Sick!! – GI hemorrhage death spiral 4. Cholestasis Vit K absorption – Vit K needed to make factors 2,7,9,10 – Long term antimicrobial Tx inhibits Vit K production – Hemorrhage elsewhere only when near death • Petechiae, bruising, bleeding into cavities Normal Liver Size • Look at the gastric axis!! (fundus to pylorus) • Normal gastric axis range: • From: perpendicular to the spine; To: parallel to the ribs. Hepatomegaly • Look at the gastric axis!! (fundus to pylorus) • Gastric axis more acute angle with the spine Hepatomegaly • Focal hepatomegaly is often, but not always neoplasia • Gallbladder mass can be mistaken for liver mass or even normal liver if filled with amorphous sludge Hepatomegaly • Focal hepatomegaly is often, but not always neoplasia • Gallbladder mass can be mistaken for liver mass or even normal liver if filled with amorphous sludge Hepatomegaly • Focal hepatomegaly is often, but not always neoplasia • Gallbladder mass can be mistaken for liver mass or even normal liver if filled with amorphous sludge Hepatomegaly • Focal hepatomegaly is often, but not always neoplasia • Gallbladder mass can be mistaken for liver mass or even normal liver if filled with amorphous sludge • Glycogen vacuolar hepatopathy can be focal • Nodular hyperplasia is a benign process causing liver masses • Generalized hepatomegaly • Primary or secondary liver disease • Toxic exposure and swelling of the liver – hypoechoic large liver with smooth borders and rounded margins • Steroid hepatopathy – hyperechoic large liver with smooth borders and normal margins • Any generally large liver with rounded margins can be neoplastic, regardless of echotexture and relative echogenicity – LSA, MCT, hepatocellular carcinoma Microhepatia - Microhepatica • Look at the gastric axis!! (fundus to pylorus) • Gastric axis more obtuse angle with the spine Microhepatia - Microhepatica Differential Diagnosis: 1. Atrophy • Portasystemic shunt – any age, chronic disease • AV fistula – usually less than 2 yrs old (rare) • Often normal panel, but elevated bile acids + ammonias Microhepatiacirrhosis - Microhepatica scites Differential Diagnosis: iver 1. Atrophy – Small, maybe hyperechoic liver • Portasystemic shunt – any age, chronic disease • AV fistula – usually less than 2 yrs old (rare) • Often normal panel, but elevated bile acids + ammonias 2. Cirrhosis • history of chronic inflammatory disease • History of massive hepatic necrosis • History of untreated PSS for years • Usually middle aged to older patients • Liver enzymes usually but not always elevated, bile acids elevated, albumin may be low • Ascites is common Microhepatia - Microhepatica Differential Diagnosis: 3. Congenital small size – diagnosis of exclusion • Imaging – no lumps, normal appearing margins, normal echotexture (just small) • All liver blood tests normal, except changes due to secondary liver disease • Liver biopsy normal • Splenic portagram normal Problems Causing Reactive Hepatopathy • Any systemic infection or inflammation – Occult - urinary tract, metritis, prostatitis, dental disease, etc. • Disease of organ drained by portal vein – Gut, spleen, pancreas (ultrasound the best test) • Hyperthyroidism in cats • Severe muscle disease • Untreated Cushing’s Disease or diabetes mellitus • Hypoxia, passive congestion – heart failure, respiratory disease, severe anemia – hypotension • Drugs causing liver enzyme induction • VARYING DEGREES OF COLLATERAL DAMAGE Diagnostics for Liver Disease First Tier Tests: • CBC, panel, urinalysis • Fecal flotation, direct smear, cytology • HWAg in the dog, FeLV/FIV in the cat Second Tier Tests: • Bile Acids • Complete Abdominal Ultrasound (not focused liver/GB and not GlobalFAST®) • Liver sampling & spleen FNA – after BMBT • FNA – 25-50% diagnostic • Ultrasound guided biopsy – 50% diagnostic • Wedge biopsy – more likely to be diagnostic Diagnostics for Liver Disease Third Tier Tests: • if Bile Acids are equivocal and PSS is suspected – Ammonia tolerance test – Splenic portagram • Coagulation tests if significantly systemically ill, severe liver disease is suspected, or liver sampling will be done • Hunt for causes of secondary liver disease • Imaging – thoracic rads and ultrasound • Testing for infectious disease and Cushing’s Disease • Diagnostic surgery, MRI/CT Pattern Recognition - Liver Disease • High liver enzymes – ALT – hepatocellular disease (hepatocellular membrane) – ALKP, GGT – more sensitive indicator of cholestasis than bilirubin (from biliary epithelium) • Low albumin – low alb indicates severe disease (90% loss of hepatic function) – Beware human labs (falsely low values) - Abaxxis • Low fasting glucose (70% loss of hepatic function) • High prost-prandial glucose • Low BUN • Abnormal cholesterol, triglycerides ALT Gems The enzyme formerly known as SGPT • RBC & skeletal muscle contain small amts of ALT – Hemolysis and muscle damage cause moderate elevations in ALT (2-3x) • ALT - t1/2 – 1-2 days – the first to improve – Starts improving within 1-2 weeks of liver disease resolution – remains elevated during hepatic regeneration • DDx hepatocellular turnover – Hepatocellular disease – Poor perfusion – hypotension, passive congestion, anemia • Marker for anaphylaxis, along with increased PTT and AFAST sonogram – Trauma – surgery, trauma, peritonitis – Toxicity ALKP Gems • Bone disease can also cause ALKP elevation – Neoplasia, osteomyelitis, hyperPTH, growth & healing • DDx cholestasis: – Gallbladder disease • Intramural - Gallbladder sludge, mucocoele, stones, infection • Mural - Gallbladder wall polyps, masses, infection • Extramural – Pancreatitis, abdominal mass, duodenal foreign body, diaphragmatic hernia • Gallbladder trauma or rupture – Liver Disease • microscopic cholestatic disease (infectious, inflammatory, toxic), liver trauma, neoplasia, lipidosis ALKP Gems • DDx cholestasis: – Systemic cholestatic disease • Endocrine – diabetes mellitus, hyperadrenocorticism, chronic stress, hyperthyroidism • Passive congestion – RHF, pericardial disease • Systemic infection/inflammation – especially sepsis, rickettsial disease, protozoal disease, fungal disease GGT Gems • less influenced by secondary liver disease or acute hepatic necrosis than ALKP • Not confounded by bone disease as ALKP • more useful in cats to identify fatty liver • More useful in dogs to identify biliary disease • Otherwise, follows ALKP Hepatotoxic Drugs • Drug induced ALKP does not necessarily indicate hepatic pathology – Assess with bile acids if concerned – Phenobarbital can also cause hepatotoxicity, but glucocorticoids almost never do • GGT increases markedly with corticosteroid enzyme induction in dogs • Drug induced ALKP takes weeks to months to resolve after stopping the drug • Glucocorticoids almost always elevate ALKP (and ALT) in dogs, but almost never in cats Hepatotoxic Drugs • Drugs that increase ALT are more likely to cause hepatic damage if continued • At a marked increase in ALT, the offending drug should ideally be stopped, and ALT rechecked in 30 days • Lomustine - missing from the chart, but can cause potentially life threatening hepatotoxicity indicated first by increased ALT and then decreased albumin • Use of any drug on either chart indicates monitoring of liver nz + bile acids, albumin Elevated Liver Enzymes in the Cat Cats are not little dogs – Thumb Rules • Cats with persistently elevated enzymes should be worked up – T1/2 of liver enzymes is hours in the cat, not days as in the dog – cats have 1/3 the liver ALKP compared to dogs • Cats with significant cholangiohepatitis can have normal liver enzymes, though that problem often causes very high ALT • GGT in cats has higher sensitivity but lower specificity for biliary disease • If a cat has biliary disease, GGT is likely high • If cat does