Steve Bradley Chief Medical Resident, HMC Inpatient Services

 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

 AST/ALT  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

 Hepatocellular injury  AST/ALT  Cholestatic  Bilirubin/alkaline phosphatase  Mixed  Isolated/predominant alkaline phosphatase elevatioin

 Hepatocellular injury  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!!

 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

 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

 >1000 to 2000  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

 Transaminases in the 1000s  Suggests ischemia/toxin/viral  IVDU  Risk of acute Hep B or acute Hep C  Cocaine  Risk of ischemia  Recent infection  Doxycycline

 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

 Sources  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  1.2

 Canicular cell injury  Alkaline phosphatase  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

 Extrahepatic  Choledocholithiasi s  Malignancy  Cholangiocarcinom a  Pancreatic cancer  Gallbladder cancer  Ampullary cancer  Primary sclerosing cholangitis  AIDS Cholangiopathy  Intrahepatic  TPN  Sepsis  Primary sclerosing cholangitis  Primary biliary cirrhosis  Intrahepatic mass

 Finding the source of obstruction  Ultrasound: good for extrahepatic cause  CT/MRI/ERCP: for both intra or extrahepatic cause  In our patient?

 46 young man with history of IVDU and long-standing alcohol use following up in clinic.  Laboratory finding  AST 68  ALT 37  Alk phos 194  TBili 1.3  Albumin 2.9

 Chronic Liver disease  Hepatitis B, Hepatitis C  NASH ( Nonalcoholic steatohepatitis )  Alcoholic liver disease  Hemochromatosis  Autoimmune hepatitis

 72 yo man fell in bathroom. Found the next day.  Laboratory  AST 167  ALT 58  Alk phos 127  TBili 1.8  Albumin 3.9

 Where else is AST and ALT found?  How can you look for evidence of muscle injury?

 CK 7260  Myoglobin  UA – 2+ blood, microscopic no RBC  Diagnosis?

 Chronic Biliary Disease  Primary biliary cirrhosis  Primary sclerosing cholangitis  Infiltrative disorder  Amyloid  Granulomatous diseases  Metastatic carcinoma  abscesses

 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

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

 Directed therapy  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