S3 CP2 Liver Disease Test

November 27, 2010

S3 CP2: Liver Disease Tests by Dr. Arnel Amata

I. II. III.

Introduction Lab tests Diseases of the Liver and its Laboratory Findings a. Hepatitis b. Cirrhosis c. Biliary Obstruction d. Cirrhosis and Hepatic Failure e. Hyperbiluruninemia i. Intrahepatic biliary tracts disease with hyperbilirubinemia ii. Hereditary Conjugated Hyperbilirubinemia 1. Dubin Johnson Syndrome 2. Rotor Syndrome iii. Hereditary Unconjugated Hyperbilirubinemia 1. Crigler Najjar Syndrome Type 1 2. Crigler Najjar Syndrome Type II 3. Gilbert Syndrome f. Viral Hepatitis g. Alcoholic Hepatitis h. Hemochromatosis

i.

Wilson Disease

THREE MAJOR CATEGORIES A. Disease from Injury to hepatocyte 1.Infection 2.Drugs or alcohol 3.Autoimmune disease 4.Inborn error of metabolism 5.Complications of pregnancy B. Disease associated with obstruction to bile flow out of the liver and into the GIT 1. Stones in the biliary tract 2. Biliary atresia C. Impaired bilirubin conjugation or excretion 1. Crigler Najjar 2. Dubin Johnson Liver disease

Liver Cirrhosis

Hepatic failure Hepatomegaly and Jaundice Lab test LAB TESTS 1. Integrity and Function • ALT/SGPT – more specific • AST/SGOT • LDH – liver disease and hemolysis

2. Protein Synthesis • Total serum protein • Serum albumin • Prothrombin time – coagulation factors 3. Serum Bilirubin Levels • Total serum bilirubin • Unconjugated bilirubin o RBC hemolysis o Incomplete conjugation of large amounts of bilirubin o Impaired uptake or conjugation • Conjugated bilirubin o Hepatocellular injury o Obstruction of bile flow into the GIT 4. Biliary Obstruction • Alkaline phosphatase (ALP) • γ – glutamyl transferase (GGT) • 5’ nucleotidase (5’ NT) DISEASES OF THE LIVER AND ITS LABORATORY FINDINGS HEPATITIS • Most common cause of hepatocellular pattern o Elevated aminotransferases o Normal or slightly increased ALP, GGT, 5’ NT BILIARY OBSTRUCTION • Request ultrasound • Increase ALP – 2-5 times • Moderate to significant increase GGT and 5’ NT • Normal or slightly elevated aminotransferases HEPATIC FAILURE AND CIRRHOSIS • Document history for: o Excess ethanol x 5yrs o Hepatitis o Hemochromatosis o Wilson disease o α1 antitrypsin o primary biliary cirrhosis o primary sclerosing cholangitis o autoimmune hepatitis HEPATIC FAILURE • Fulminant hepatic failure o severe liver injury o hepatic encephalopathy after 8 weeks of symptoms or 2 weeks after jaundice o viral hepatitis o drugs, chemicals o portal vein thrombosis o metabolic – AFLP, Wilson • Stages

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o Grade I – confused or altered state o Grade II – inappropriate behaviour or drowsiness o Grade III – stuporous but arousable with marked confused behaviour o Grade IV – comatose and unresponsive to painful stimuli • Portal hypertension • Hepatorenal syndrome • Grave prognosis o PT > 30 sec o Total bilirubin (?) 17.5 mg/dl o Age < 10, > 40 o Hepatitis A or b infection o > 7 days jaundice Laboratory Findings TB and B1 Markedly elevated PT Elevated Aminotransf Increase and decrease rapidly erases Serum Often elevated creatinine Others Glucose Decreased WBC Increased Platelet Decreased albumin Decreased CIRRHOSIS • End stage • Fibrosis and scarring • Nodules: micro < 3mm, macro >3mm • Alcoholism 60-70% • Chronic viral hepatitis 10% • Biliary disease 5-10% • Primary hemochromatosis 5% • Cryptogenic 10-15% • Wilson, alpha 1 antitrypsin Laboratory Findings Biopsy TB, B1 AST, ALT ALP, GGT, 5’NT Serum albumin PT

Nodules and fibrous septae Elevated Increased but not very high Elevated Low elevated

HYPERBILIRUBINEMIAS • Bile – solubility of fat • Increased bilirubin formation or decreased excretion • Jaundice – yellow discoloration of the skin and sclerae • Cholestasis – retention of bilirubin and components of bile in the liver Causes: • Increased bilirubin formation or decreased excretion

Types and its Causes: • Extrahepatic biliary obstruction o Gallstones o Carcinoma of pancreas o Structural deformations o Congenital duct malformations o Biliarty strictures and cysts o Extrahepatic primary sclerosing cholangitis o Flukes • Decreased bilirubin excretion from liver (conjugated) o Dubin Johnson Syndrome o Rotor Syndrome o Drug induced impairment of excretion o Primary biliary cirrhosis o Primary sclerosing cholangitis • Unconjugated hyperbilirubinemia 3 groups: o Excess bilirubin  Hemolytic anemias, inneffective erythropoiesis o Reduced hepatic uptake of bilirubin  Drug, Gilbert syndrome o Impaired conjugation  Decreased UDP glucoronyl transferase – physiologic  Crigler Najjar Syndrome I and II – pathologic INTRAHEPATIC BILIARY TRACTS DISEASE WITH HYPERBILIRUBINEMIA • Primary Biliary Cirrhosis o 40-50 y/o Female o (+) antimitochondrial bodies o Increase IgM 40-50% o Liver Function Test  Markedly elevated ALP, GGT, 5’NT  Normal or slightly elevated AST, ALT  Normal serum bilirubin – progressively increase • Primary Sclerosing Cholangitis o Inflammation of biliary tree o Bacterial infection and abscess o “BEADING” o Unknown cause o Males, 39 years o Coexist with IBD’s o Lab Test  Increase ALP, GGT, 5’NT  Bilirubin normal and increased progressively  Hypergamma globulinemia 30% HEREDITARY CONJUGATED HYPERBLIRUBINEMIA Dubin Johnson Syndrome • Mild Jaundice • Elevated conjugated bilirubin

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• Unknown etiology • LIVER: black pigment • After puberty Laboratory Findings TB, B1 TB 2-5 mg/dl, 50% conjugated RBC Hemolysis None LFT except bilirubin Normal Coproporphyrin in Reduced to half urine normal Urinary 85% of total UCP’s coproporphyrin I Rotor Syndrome • Hereditary • Unknown • Symptomatic • Accidental discovery of elevated conjugated bilirubin • Absence of pigment Laboratory Findings TB, B1 TB 2-5 mg/dl, 50% conjugated RBC Hemolysis None LFT except bilirubin Normal Coproporphyrin in 2.5-5x elevated urine Urinary 70% of total UCP’s coproporphyrin I HEREDITARY UNCONJUGATED HYPERBLIRUBINEMIA Crigler Najjar Syndrome Type 1 • Very rare • Fatal • Infancy • Absence of UDP-GT Laboratory Findings TB, B1 Inc 15-50 mg/dl RBC Hemolysis None LFT except bilirubin Normal Crigler Najjar Syndrome Type II • Reduced UDP-GT Laboratory Findings TB, B1 Inc 6-25 mg/dl RBC Hemolysis None LFT except bilirubin Normal Gilbert Syndrome • Relatively common 5% of general population • Young adults with mild jaundice • Drug or fasting • Reduced UDP-GT • Asymptomatic • Mild jaundice in healthy adolescents Laboratory Findings TB, B1 < 3 mg/dl unconjugated RBC Hemolysis None

LFT except bilirubin

Normal

VIRAL HEPATITIS • Marked elevated aminotransferases • Limited increase in ALP, GGT, 5’NT • Serologic Assays • Viral genomic DNA ALCOHOLIC HEPATITIS • 3-4 alcoholic drinks/ day Laboratory Findings GGT Widely used to detect status Elevated with excess ethanol Aminotransferases Elevated PT Elevated HEMOCHROMATOSIS • 40-50 males Laboratory Findings Total serum iron TIBG Serum ferritin Genetic test Serum glucose Liver biopsy

Markedly increased Normal or low Markedly increased HFE gene mutation Increased Iron deposits in hepatocytes and Kupffer cells

WILSON DISEASE • Accumulation of copper • Liver, brain, eye • Hepatolenticular degeneration Laboratory Findings Serum ceruloplasmin 24 hr urinary Cu excretion LFT Serum copper Hepatic copper

Dec < 20 mg/dl > 100 ug copper/ 24 hrs Normal or becom abnormal Elevated, normal or low 250- 300 ug/ g (N1455 ug)

a1- ANTITRYPSIN DEFICIENCY • Most common genetic cause of liver disease in infants and children • Empysema • 1:1600 to 2000 • 10-15% suffer liver damage • Lab tests o Serum alpha1- antitrypsin: < 57 mg/dl o Isoelectric focusing and agarose electrophoresis o Polymerase chain reactions o Liver function test o Liver biopsy- red cytoplasmic granules (+) PAS diastate resistant

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HEPATOCELLULAR CARCINOMA • Associated with history of cirrhosis • AFP • CEA • Not useful for screening or diagnosing • Histopathologic exam is necessary After Chirstmas season comes New Years Day and as we welcome 2011 we the patho-team suggests you guys some resolution that will guide you to SUCCESS next year!  Enjoy

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Just for today, I will not sit in my living room all day in my nightdress. Instead, I will move my computer into the bedroom. I will no longer waste my time relieving the past, instead I will spend it worrying about the future.

MERRY CHRISTMAS and HAPPY NEW YEAR from the Patho-Team!  Have a meaningful holiday!

I will do less laundry and use more deodorant. I will avoid taking a bath whenever possible and conserve more water. I will give up chocolates totally. 100%. Completely. Honestly.... I will try to figure out why I *really* need nine e-mail addresses. I will stop sending e-mail, Instant Messages and be on the phone at the same time with the same person. I will spend less than one hour a day on the Internet. This, of course, will be hard to estimate since I'm not a clock watcher. I will read the medical books... just as soon as I can find it. I will think of a password other than "password." I will not tell the same story at every get together. I won't worry so much. I will cut my hair. I will grow my hair. I will stop considering other people's feelings when they so obviously don't consider mine - if that unwashed fellow sits next to me again, I'll tell him he stinks! I will be more imaginative.

I will not hang around girls - they think you love them and that sucks. (Feeling mo! Gwapo ka?) At kung mahirap parin ang mga resolutions sa tass.. bakit di mo itry tong sa baba…

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Spend more time watching TV / movies. Chat more over phone / Internet. Read less. I want to gain weight. Put on at least 30 pounds. Stop exercising. Waste of time. Procrastinate more. Drink. Drink some more. Start being superstitious. Spend more less time at school.

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