Interpretation of Liver Function Test Dr. Wongsakorn Boonkarn Medicine

Liver Function Test Total / Direct bilirubin SGOT (AST), SGPT (ALT) Alkaline phosphatase GGT Albumin/ Globulin

Hyperbilirubinemia TB ≥ 2-3 mg/dl = Jaundice Elevated Bilirubin Hyperbilirubinemia TB ≥ 2-3 mg/dl = Jaundice

Types of Hyperbilirubinemia Indirect Hyperbilirubinemia ( IB > 80% ) Direct Hyperbilirubinemia ( DB > 50% )

Heme Biliverdin Indirect bilirubin Bilirubin Metabolism Heme Biliverdin Indirect bilirubin Indirect hyperbilirubinemia Direct bilirubin UDP-GT hepatocyte Enterohapatic circulation Bile duct UDP glucuronosyltransferase Intestine Bacteria Urobilinogen urine

Heme Biliverdin Indirect bilirubin Bilirubin Metabolism Heme Biliverdin Indirect bilirubin UDP-GT Direct bilirubin hepatocyte Direct hyperbilirubinemia Enterohapatic circulation Bile duct Intestine Bacteria Urobilinogen urine

Jaundice & Hyperbilirubinemia Indirect IB > 80% Direct DB > 50% Mild jaundice Normal urine color (may be dark in intravascular hemolysis) - Urine bile -ve Mild to marked jaundice Dark urine - Urine bile +ve

Causes of Indirect Hyperbilirubinemia RBC Hemolytic jaundice Liver Inherited disorder (Gilbert’s disease) Congested liver (CHF) Thyrotoxicosis

Causes of direct Hyperbilirubinemia Liver Hepatocellular jaundice Intrahepatic cholestasis (medical cholestasis) Biliary tract Obstructive jaundice (extrahepatic cholestasis

Hepatocellular Jaundice Key Features Symptoms & sign - Malaise, weakness, anorexia and N-V - Degree of jaundice varies - Dark urine - Normal-colored stool LFT - TB varies - DB > 50% of TB - ↑ SGOT/SGPT > 5X - ALP < 3X Urine - Urine bile +ve

Hepatocellular Jaundice Common Causes of Hepatocellular Jaundice Alcohol Viral hepatitis Drug & Herb

Hepatocellular Jaundice Less Common Causes of Hepatocellular Jaundice Ischemic hepatitis Systemic infection (DHF, typhoid, typhus) HSV, CMV, EBV Autoimmune hepatitis Wilson’s disease Acute fatty liver of pregnancy Acute CBD obstruction Acute Budd-Chiari syndrome

Acute viral Hepatitis HAV, HBV Prodomal symptomes: flu-like, malaise, N-V before the onset of jaundice Fever disappears after jaundice begins AST/ALT level usually < 2000 U/L AST < ALT Serology - Anti HAV igM - HBsAg, anti HBc IgM

Alcoholic Hepatitis Heavy, continued drinking Fever, jaundice, malaise, N-V AST/ALT level usually < 300 U/L AST > ALT (usually > 2x) - Alcohol induces release of mitochondrial AST from cells without visible cell damage - Pyridoxine deficiency decreases hepatic ALT activity

Drug-Induced Hepatitis Both modern drugs and herbs can cause hepatitis Onset of exposure usually within 1 mo ( but can be to 3 mo ) Mechanisms Direct toxic effect : Paracetamol Idiosyncrasy : sulfa, phynytoin, CBZ, PTU, anti TB, etc Patterns of LFT vary Diagnosis by exclusion of other causes

LFT clues in Acute Hepatocellular injury Level of aminotranferase Predominant AST or ALT Rate of aminotransferase declination

Level of Aminotransferase Mild ALT elevation (1-2 xULN) is non-specific and usually normal when repeated Alcoholic hepatitis : < 300 U/L Viral hepatitis : Rarely > 2,000 U/L Marked ALT elevation ( > 15-20 xULN) - Ischemic hepatitis - Acute BCS - Drug & toxin : particularly PCM & mushroom ALT level poorly correlated with the extent of hepatocellular injury

Rate of Aminotrasferase Declination Rapid ALT declination - Ischemic hepatitis - Acute CBD obsteruction - Acute BCS Slow ALT declination - Viral hepatitis : 10% /day or 50% /week - Drug-induced (varies) - Autoimmune and metabolic disease

Predominant AST (AST/ALT ratio > 1) Alcoholic hepatitis - AST/ALT ratio usually > 2 Wilson’s disease Any hepatitis flare in cirrhosis Ischemic hepatitis Some drug

Cholestasis Jaundice Key Features Symptoms & sign - Jaundice - Pruritus - Dark urine - Pale stool LFT - TB varies - DB > 50% of TB - ↑ SGOT/SGPT < 5X - ALP > 3X Urine - Urine bile +ve

Causes of Elevated ALP (+ GGT) Liver Intrahepatic cholestasis (medical cholestasis) SOL Infiltrative liver disease Biliary tract Obstructive jaundice (extrahepatic cholestasis

Common Causes of Extrahepatic Cholestasis Extrinsic cancer Fixing and compressing duct intrinsic cancer Impacted stone Stricture

Common Causes of Intrahepatic Cholestasis Drugs (phenothiazines, estrogen, anabolic hormones, erythromycin, arsenic, ect Sepsis Congested liver (from RHF) Thyrotoxicosis Primary biliary cirrhosis Benign post-operative cholestasis ICU jaundice

Differentiate Causes of Elevated ALP Obstructive Jaundice IHC ILD SOL Pruritus, Pale stool Yes (may be absent in first few weeks) Yes or No Rare TB level < 25-30 mg/dl (except in the presence of ARF or hemolysis) Up to 50-60 mg/dl Less prominent Than ALP and Occurs late ALP level Almost always Elevated CBD stone <500 Malignancy varies 3x to > 10x Varies, but May be normal Varies from 3x to >10x US Dilated IHD ± CBD (esp. TB > 12 mg/dl) Normal Mass

ϒ-Glutamyl Transpepetidase (GGT) Usefulness of GGT Exclusion elevated ALP from bone Elevated GGT without elevated ALP Physiology -- infant < 1 yr and after 60 yr Others -- DM, acute pancreatitis, MI -- Alcohol -- Drug : phenytoin, phenobarb, CBZ, rifampicin antidepressants -- Hyperthyroidism -- Obesity, anorexia nervosa

Alumin / Globulin Albumin Hypoalumin Globulin Hyperglobulinemia Liver synthesis half life 14-20 day Hypoalumin - liver disease Malnutrition NS Protein loosing enteropathy Chronic disease Globulin WBC synthesis inflammation Hyperglobulinemia Cirrhosis Chronic infection Auto immune liver disease MM