Abnormal Liver Test!by !

George Vagujhelyi M.D.!

1!

Liver Enzymes!

•  AST asparate aminotransferase!

•  ALT alanine aminotransferase!

•  Alkaline phosphatase!

•  GGT Gamma-glytamyl transpeptidase!

•  5’-nucleosidase!

•  LDH lactate dehydrogenase!

•  AST: found in hepatocytes, skeletal and cardiac muscle and other organs.!

•  ALT: relatively specific for liver injury!

•  ALP: found in bone, liver and placenta!

•  Prothrombin time:!

•  marker of liver function !

•  factors II,V,VII,and X synthesized in the liver, !

•  factors are dependent on Vit K!

•  Vit K deficiency: antibiotics, prolonged fasting, SB disorder(celiac)!

•  Albumin: prolonged illness, cancer!

•  elevations in liver enzymes reflect damage to the liver or biliary obstruction!

•  abnormal serum albumin or prothrombin time seen in impaired hepatic synthetic function!

•  bilirubin reflects the ability of the liver to detoxify metabolites and transport organ anions into bile!

Evaluation!

•  History: this helps identify potential risk factors!

•  Family history!

•  ETOH consumption!

•  >210 gm/wk men, >140gm/wk women 2yrs!

•  Drugs !

•  prescription, OTC, herbal, dietary!

•  Travel!

•  Transfusion prior to 1992!

•  Medical conditions!

•  right sided heart failure!

•  DM, !

•  obesity,!

•  pregnancy, !

•  IBD,!

•  Celiac,!

•  thyroid!

Physical exam!•  Temporal and proximal muscle wasting!

•  spider nevi, palmar erythema, gynecomastia and caput medusae!

•  Ascities!

•  Hepatic encephalopathy!

•  Dupuytrens contractures, testicular atrophy!

•  Right sided pleural effusion!

•  liver and spleen size!

Acute !•  generally less then 3 months !

•  can produce levels more then 1000, ALT>AST!

•  associated with malaise, anorexia, abdominal pain and jaundice!

•  Hepatitis A,: exposure hx!

•  Hepatitis B risk factors!

•  drug induced!

•  alcoholic hepatitis ( AST>ALT,2:1, levels 400) !

•  ischemia, hypotensive event!

•  Wilsons disease!

Dx!

•  Actaminophen!

•  Toxicology!

•  Acute hepatitis !

•  IgM anti-hepatitis A!

•  HBsAg and IgM anti-hepatitis B core!

•  HCV RNA!

•  Autoimmune markers(ANA,ASMA)!

•  Ceruloplasmin if <40 yrs usually less the 20mg/dl)!

•  U/S!

Chronic !•  > 3 months of elevated enzymes!

•  2-5 times ULN!

•  usually asymptomatic, slight fatigue and RUQ pain!

•  Causes!

•  Hepatitis C, B, !

•  NAFLD!

•  hemochromatosis!

•  AIH !

•  Alcoholic liver disease.!

Mild Chronic AST/ALT !•  Medications!

•  Chronic B or C (HBsAg,HBsAb, HB PCR, HCV)!

•  Screen for alcohol abuse (AST/ALT >2:1)!

•  Hemochromatosis(iron studies,Ferritin >400?)!

•  NAFLD ( imaging U/S,CT)!

•  AIH!

•  Wilson ( ceruloplasmin,Kaiser-Fleisher rings, urine copper)!

•  Thyroid!

•  Celiac disease!

Mild Chroinc AST/ALT!•  Medication!

•  Timing!!!

•  Antibiotics, antidepressants, lipid lowering drugs,sulfonamides,salicylates NSAIDS,anti-epileptics anti TB!

•  OTC!

Mild Chronic AST/ALT!•  Viral hepatitis!

•  Exposure history!

•  Travel !

•  Serology studies!

•  HBsAg,HBsAb,Hepatitis B core,HCV!

Hereditary Hemochromatosis!•  common disorder 1: 200-300 white persons are homozygous!

•  1:10 are heterozygous !

•  Family history!

•  Screening!

•  serum Fe and TIBC get a transferrin saturation >45%!

•  Ferritin >400 (acute phased reactant)!

•  dx with genetic testing/liver biopsy !

Mild Chronic AST/ALT !•  Fatty Liver/NAFLD!

•  it is a hepatic manifestation of !

•  metabolic syndrome!

•  obesity!

•  type 2 DM !

•  hyperlipidemia!

•  Dx!

•  U/S!

•  CT!

Mild Chronic AST/ALT!•  Who to observe!

•  general approach to a “first-time” increase in LFT’s!

•  asymptomatic, incidental finding!

•  rule out !

•  risk factors!

•  LFT’s less then 2 time normal!

•  liver function is preserved!

•  it is reasonable to observe but if there is a change then further evaluation is required.!

Jaundice!•  Bilirubin greater then 2.5 mg/dl!

•  determine whether it is conjugated vs unconjugated.!

•  common unconjugated disorder is Gilbert syndrome!

•  total bilirubin is about 3 mg/dl, direct bilirubin is about 0.3mg/dl!

•  under periods of stress,illness, fasting an isolated elevated Tbil with normal, LFT’s and Hgb. !

•  Obstructive !

•  abdominal pain, fever, palpable GB!

•  Non obstructive !

•  hepatocellular dysfunction!

Isolated Hyperbilirubinemia unconjugated!

•  Increased bilirubin production !

•  Hemolysis!

•  Hemotoma!

•  Impaired hepatic uptake!

•  heart failure!

•  Portosystemic shunts!

•  drugs- rifampin and probenecid!

•  Impaired bilirubin conjugation!

•  Gilberts!

•  Thyroidism!

Hyperbilirubinemia conjugated!

•  Extrahepatic!

•  CBD stones!

•  PSC!

•  Acute and Chronic Pancreatitis!

•  Intrahepatic !

•  viral hepatitis!

•  alcoholic hepatitis!

•  NASH!

•  cirrhosis!

•  Drugs!

•  Sepsis!

•  TPN!

•  infiltrative diseases!

!!

Alkaline phosphatase !!!!!!!

alkaline !

•  Determine if an isolate ALP is from the liver check a GGT.!

•  ALP can also be fractionated to see if coming from the bone, liver or placenta.!

•  If isolated but coming from the liver think of!

•  chronic cholestatis( partial biliary obstruction, PBC,PSC)!

•  infiltrative process( amyloidosis,sacroidosis, cancer)!

•  may have normal bilirubin!

•  DX!

•  U/S, ERCP,MRCP and CT!

•  intrahepatic causes; (if imaging studies normal)!

•  AMA, drug hx, liver biopsy?!

Cholestatic disorders!disease! clue! dx!

PBC! middle age female! AMA!

PSC! UC! MRCP,ERCP!

Large bile duct!

jaundice and pain!

U/S,ERCP MRCP!

drug induced!

meds and timing! w/drawal!

infiltrative! amyloid,!sarcoid! CT, US!

inflammatory! inflammation! bd cultures!

Questions!

•  A 60 yr old man is brought to the ER, by his wife who admits that the patient has a drinking problem and has been complaining of back pain for several days.!

•  PE : spider nevi and palmar erythema, liver edge is firm and spleen is palpable.!

•  labs: Hgb 11.9, PLT 130 AST 4200 ALT 5100, total bili 3.1mg/dl ALP 70 U/L, INR 1.6!

•  whats the most likely cause!

•  pancreatic cancer!

•  Acute hep A!

•  Acetaminophen toxicity!

•  ischemic hepatitis!

•  Alcoholic hepatitis!