Steve Bradley Chief Medical Resident, HMC Inpatient Services Liver Function Tests Steve Bradley Chief Medical Resident, HMC Inpatient Services

What are “Liver Function Tests” Few are truly associated with function Albumin: protein synthetic function INR: clotting factor synthesis Most are related to cell injury Patterns point to specific cell injury

Tests of Liver Injury AST/ALT Alkaline Phosphatase/GGT Cytoplasmic enzymes found in hepatocytes Very sensitive marker for hepatocyte injury Specificity is poor (other sources, e.g. muscle) Mitochondrial isoenzyme AST increased by ethanol (explains 2:1 ratio) Alkaline Phosphatase/GGT Canicular enzymes Gradual increase in plasma levels with obstruction of canicular flow

Patterns of Enzyme Elevation Hepatocellular injury AST/ALT Cholestatic Bilirubin/alkaline phosphatase Mixed Isolated/predominant alkaline phosphatase elevatioin

Caveats to Patterns Hepatocellular injury Cholestatic Also results in release of bilirubin Alkaline phosphatase also found in hepatocyte Cholestatic Biliary obstruction can lead to hepatocellular injury History and Physical guide your thinking!!

Patient #1: Suzie Duzie Presents with two days of fever, abdominal pain, yellow skin, nausea, vomiting. Labs demonstrate the following: AST 3210 ALT 3060 Alk phos 249 TBili 6.2 (Direct 4.3) Albumin 3.1 INR 1.2

What targets the hepatocyte? Toxins Alcohol Medications Tylenol Mushrooms Viral Hepatitis A/B/C EBV/HSV/CMV Ischemia Severe hypotension Vasoconstriction Sepsis Autoimmune Wilson’s Alpha-1 antitrypsin deficiency

Degree of elevation points to etiology Ischemia Toxin Virus >500 to 1000 Acute biliary obstruction <300 Alcoholic liver disease, cirrhosis, chronic obstruction AST/ALT>2 and each <300 suggests EtOH or cirrhosis If >500, unlikely EtOH

Back to our patient Transaminases in the 1000s IVDU Cocaine Suggests ischemia/toxin/viral IVDU Risk of acute Hep B or acute Hep C Cocaine Risk of ischemia Recent infection Doxycycline

Patient #2: Ima Hurtin 40 year-old overweight woman presents with right UQ abd pain, fever, chills. Previous episodes after fatty meals. Laboratory Studies AST 67 ALT 57 Alk Phos 293 TBili 4.1 (Direct 2) Albumin 4 INR 1

Increased Bilirubin Sources Conjugated=direct=processed by liver Increased production Hemolysis, hematoma reabsorption Impaired uptake/conjugation Dubin-Johnson, Gilbert’s Impaired excretion Renal failure, biliary obstruction Conjugated=direct=processed by liver Unconjugated=indirect=not processed by liver Fractionation – helpful to assess for unconjugated hyperbilirubinemia < 20% direct AND indirect >1.2

Biliary Obstruction Canicular cell injury Alkaline phosphatase GGT Liver and bone major sources Increased synthesis and release in liver disease Up to 3x normal in variety of liver disease GGT Sensitive indicator of canicular cell injury Parallels alkaline phosphatase increase when of liver origin

Causes of Biliary Obstruction Extrahepatic Choledocholithiasis Malignancy Cholangiocarcinoma Pancreatic cancer Gallbladder cancer Ampullary cancer Primary sclerosing cholangitis AIDS Cholangiopathy Intrahepatic TPN Sepsis Primary sclerosing cholangitis Primary biliary cirrhosis Intrahepatic mass

How would you like to approach this patient? Finding the source of obstruction Ultrasound: good for extrahepatic cause CT/MRI/ERCP: for both intra or extrahepatic cause In our patient?

Patient #3: Biggie Smalls 46 yo man with history of IVDU and long-standing alcohol use following up in clinic. Laboratory AST 68 ALT 37 Alk phos 194 TBili 1.3 Albumin 2.9

Mixed Patterns of Elevated Liver Function Chronic Liver disease Hepatitis B, Hepatitis C NASH Alcoholic liver disease Hemochromatosis Autoimmune hepatitis

Patient#4: Iva Fallen 72 yo man fell in bathroom. Found the next day. Laboratory AST 167 ALT 58 Alk phos 127 TBili 1.8 Albumin 3.9

What else do you want to know? Where else is AST and ALT found? How can you look for evidence of muscle injury?

Additional Laboratory CK 7260 Myoglobin 23390 UA – 2+ blood, microscopic no RBC Diagnosis?

Isolated or Predominant Alk Phos Chronic Biliary Disease Primary biliary cirrhosis Primary sclerosing cholangitis Infiltrative disorder Amyloid Granulomatous diseases Metastatic carcinoma abscesses

Last Case: Sue Sadd 32 yo woman, depressed, “took some pills” a few days ago Laboratory AST 1450 ALT 1620 Alk phos 242 TBili 8 (direct 4) Albumin 2.9 INR 1.7

Fulminant Hepatic Failure Rapid development of severe acute liver injury with impaired synthetic function and encephalopathy Previously had a normal liver or had well-compensated liver disease

Causes

Treatment Directed therapy Liver transplant Acetaminophen - mucomyst Acute fatty liver of pregnancy - delivery of infant Amanita mushroom poisoning - penicillin and silibinin Wilson's disease - D-penicillamine Herpes Simplex Infection – acyclovir Liver transplant