Liver Function/Hepatitis Flashcards
Vascular and hematologic functions of the liver
Blood storage
Bacterial and foreign particle removal
Synthesis of clotting factors
Produce bile to absorb fat-soluble vitamins
Reticuloendothelial system produces monocytes, macrophages, antigens
What minerals and vitamins are stored by the liver?
Vitamin A Vitamin D Vitamin B12 Iron Copper
How are liver abnormalities classified?
Liver function/synthesis: Prothrombin (PT/INR) and albumin
Hepatocellular markers: Aminotransferases, ALT & AST
Cholestatic Markers: Alkaline phosphatase and bilirubin
Role of PT/INR and albumin in assessing liver?
Monitors synthetic function in acute and chronic liver disease
Unreliable markers if taking warfarin, nephrotic syndrome, malabsorption, or malnutrition
Liver Function Tests (LFTs)
ALT - Alanine aminotransferase (SGPT) ALP - Alkaline phosphatase (SGOT) GGT - Gamma-glutamyl transpeptidase LAP - Leucine aminopeptidase 5'-Nucleotidase
Viral hepatitis ALT/AST ratio
> 1
About equal
Causes of increased ALT?
Damage to liver parenchymal cells
Liver disease
Viral hepatitis
What causes an increase in ALP1?
Liver pathology with increase in 5’-nucleotidase
What causes an increase in ALP2?
Bone pathology with normal 5’-necleotidase
What causes significant increases in ALP?
Extrahepatic and intrahepatic biliary disease
Cirrhosis
What causes increases in GGTP levels?
Biliary obstruction
Cholangitis
Cholecystitis
Elevations after acute MI
What causes increases in LAP?
Liver disorders
Parallels ALP
Useful in differential diagnosis of increased ALP
What causes increases in 5’-nucleotidase?
Increased ALP + 5’-nucleotidase = liver pathology
Specific to cholestasis (bile formation and flow obstruction)
Similar to GGT
What are the hepatocellular markers?
Aminotransferases
ALT, AST
Young healthy adults and mild ALT/AST elevations considerations
<5x upper limit of normal seen commonly in healthy young adults
Workup if persists >6mos
Causes of persistent elevations in ALT/AST
Hepatitis B, Hepatits C, Wilson’s disease, hemochromatosis, autoimmune hepatitis, medications, Celiac’s, alpha1-antitrypsin deficiency, fatty liver
What does ALT>AST indicate?
Inflammation - drugs or infection
What does AST>ALT indicate?
Alcohol use usually
May be associated with APAP use or statins
What do severe elevations in AST or ALT (>1000) indicate?
Infection
Toxins
Shock liver
What causes ALT elevations?
Pneumonic
Avandia (rosiglitazone) and Actos (pioglitazone),
Liver infection
Therapeutic agents and toxins
What causes AST elevations
Pneumonic
Alcohol
Statin
Tylenol
What can cause AST/ALT elevations 1-5x the norm?
Alcohol use, skeletal muscle injury r/t seizure, protracted immobilization
What can cause AST/ALT elevations >5x the norm?
Infectious hepatitis
Significance of GGT elevations?
Normal GGT 0-45 U/L
Marked sustained elevation with binge drinking and high alcohol intake
What are the cholestatic markers?
ALP
- Not liver specific
- Seen in bone, intestine, lung, placenta
Bilirubin
What are the GGT, 5-Nucleotidase, and LAP relationships to ALP in liver etiology?
Parallels
What can cause isolated increases in indirect bilirubin?
Indirect unconjugated bilirubin is a byproduct of normal RBC breakdown
Not excreted in urine
Not liver disease
Hemolysis or Gilbert’s syndrome
What can cause increases in direct conjugated bilirubin?
Direct bilirubin is water soluble, can be excreted in urine
Increases seen in cholestasis
How to distinguish etiology in patients who present with both hepatocellular and cholestatic abnormalities?
AST, ALT elevations
LAP, ALP, GGT, 5-N
One usually predominates to guide diagnosis
What does NAFL stand for?
Non-alcoholic fatty liver
What does NASH stand for?
Non-alcoholic steatohepatitis
What are the complications of NASH?
Steatosis and inflammation which can lead to cirrhosis, liver failure, and cancer
When do you workup NAFL?
Workup incidental finding on imaging:
S/S of liver disease or abnormal liver biochemistries: Full NAFLD workup
No s/s and normal liver biochemistries: assess risk factors and alternate causes (ETOH, meds)
Asymptomatic and have normal liver biochemistries - liver biopsy not recommended
How is heavy alcohol use defined?
Men: 4> drinks per day or >21 drinks on average per week
Women: 3> drinks per day or >14 drinks on average per week
NAFLD and Alcohol considerations
Should not consume heavy amounts of alcohol
No recommendation for non-heavy consumption
NAFLD Management
Minimize alcohol use Manage CVD risk factors and diabetes Hep A and Hep B immunizations if serologically negative PPSV-23 age 19-64 Bariatric surgery Refer to hepatologist
Medications and NASH in NAFLD
Atorvastatin-found to be safe NAFLD
Pioglitozone DM2 Tx- Not as primary therapy
Metformin?-recent studies have not shown improvement histology
Vitamin E 400 IU for those advanced fibrosis on bx without DM or CAD
UDCA (ursodeoxycholic acid) and Omega-3
What do IgM and IgG elevations in hepatitis signify in relation to chronicity?
IgM first response, acute
IgG response later, subacute or chronic
Acute Hepatitis A
Diagnostics
IgM anti-HAV
IgM Antibody to HAV
HepA Previous exposure & Immunity Diagnostics
Total Anti-HAV
Total antibody to HAV
HepB Diagnostic Components
Central core (c) antigen (ag) Surrounding envelop (e) Surface (s) antigen (Ag)
HBcAg core antigen
HBeAg envelop antigen
HBsAg surface antigen
HBcAb
HBeAb
HBsAb
What does +HBsAg signify?
Acute antigen infection or chronic infection
What does +HBeAg signify?
Acute active infection
Highly infectious
What does +IgM HBcAb signify?
Acute infection
What does +HBsAb signify?
Previous exposure
Permanent immunity
What does +HBeAb signify?
Acute infection resolution
HepC Diagnostics
Anti-HCV
ELISA, PCR
HepD Diagnostics
HDAg - early infection
Anti-HDV - later infection
HepE Diagnostics
IgG and IgM antibodies
in progress
When do HepG infections occur?
Only seen with concurrent HepB or HepC infections, never alone
Interpret
HBsAg - neg
HBcAb - neg
HBsAb - neg
Susceptible to HBV
Interpret
HBsAg - neg
HBcAb - pos
HBsAb - pos
Immune due to natural HBV infection
HBcAb as indicator for infection vs vaccine
Interpret
HBsAg - neg
HBcAb - neg
HBsAb - pos
Immune due to HBV vaccine
Interpret HBsAg - pos HBcAb - pos HBcAb IgM - pos HBsAb - neg
Acute HBV infection
IgM acute, early infection indicator
Interpret HBsAg - pos HBcAb - pos HBcAb IgM - neg HBsAb - neg
Chronic HBV infection
Indicator for chronic infection is positive HBsAg and HBcAb with IgM negative
Interpret
HBsAg - neg
HBcAb - pos
HBsAb - neg
May be: Resolved infection (most common) False-positive HBcAb, thus susceptible Low level chronic infection Resolving acute infection
Hepatitis A
Overview
ROT: Fecal-oral
Sequelae: Survive or die
Vaccine available
PEP with HAV IgG for close contacts
Acute infection: HAV IgM confirms active infection, elevated liver enzymes
Total anti-HAV/HAV IgG confirms past infection
Hepatitis B
Overview
ROT: Blood, body fluids
Sequelae: chronic HBV infection, hepatocellular carcinoma
Vaccine available
PEP with HBV IgG for blood or body fluid exposure
Acute disease: HBsAg, HBeAg extra contagious, elevated liver enzymes
Chronic disease: No symptoms, Normal or slightly elevated liver enzymes, HBsAg
Past infection: HBsAb
Hepatitis C
Overview
ROT: Blood, body fluids
Sequelae: chronic HCV infection, hepatocellular carcinoma
No vaccine
No PEP
Acute disease: Anti-HCV, HCV viral RNA, elevated liver enzymes
Chronic disease: Anti-HCV, HCV viral RNA, no symptoms, Normal or slightly elevated liver enzymes
Past infection: Anti-HCV, HCV RNA absent, normal hepatic enzymes
Hepatitis B
Exposure Treatment
PEP: HBIG and HBV vaccine
Hepatitis A Exposure Treatment
HAV IgG within 2 weeks
