LFTs Flashcards
AST locationin hepatocyte/organ exp
cytosol and mitochondria
liver, heart, muscle, blood
ALT location in hepatocyte/organ exp
cytosol
liver only
AST:ALT ratio
Typically ratio is 1 seen in cirrhosis
Impaired plasma clearance of AST by sinusoidal cells?
Ratio >2 suggestive of alcoholic liver disease
Lower ALT from hepatic deficiency of pyridoxine (B6) in alcoholics which is cofactor for enzymatic activity of ALT
Preferential alcohol-induced injury to mitochondria enriched in AST
etiology of mild (
Hepatic: Chronic HBV and HCV Acute viral hepatitis (A-E, EBV, CMV) Steatohepatitis Alcohol-related liver injury (AST predominant) Hemochromotosis Autoimmune Hepatitis Alpha1-Antitrypsin deficiency Wilson’s disease Celiac disease Cirrhosis
Non-Hepatic: Hemolysis Myopathy Thyroid disease Strenuous exercise
increased AST and ALT
H&P
D.c hepatotoxic meds
Alk phos, bilirubin, INR, albumin, viral hepatitis serologies, iron studies
Neg serologies, w sx
Ultrasound, ANA, anti-smooth muscle antibody, ceruloplasmin, alpha 1-antitrypsin
liver biopsy
Negative serologies, asx
Lifestyle modification
repeat liver chem in 3-6 mo
Etiology of sever (>15x nml) AST and ALT elevations
Acute viral hepatitis (A-E, herpes) Medications/toxins Ischemic hepatitis Autoimmune hepatitis Wilson’s disease Acute Budd-Chiari syndrome Hepatic artery ligation or thrombosis
Alkaline phosphatase: action, location in tiss, elev in
Hydrolase enzyme responsible for removing phosphate groups from nucleotides, proteins and alkaloids
Present in nearly all tissues: Liver, localized to microvilli of bile canaliculus Bone Placenta Intestine
Elevated in Cholestatic or infiltrative diseases of liver Obstruction of biliary system Bone disease Pregnancy
Alk phos hepatobiliary vs nonhepatobiliary origin
Isoenzyme determination (helps w/ location)
5’-nucleotidease
Significantly elevated only in liver disease, highest levels in cholestatic diseases
gamma-glutamyltransferase (GGT)
Not present in bone
Elevated after alcohol consumption and almost all types of LIVER disease (can be elevated in a number of conditions)
Causes of elevated alk phos: hepatobiliary
Bile duct obstruction Primary biliary cirrhosis (PBC) Primary sclerosing cholangitis (PSC) Medications Hepatitis Cirrhosis Infiltrating disease of liver
nonhepatic causes for elevated alk phos
Bone disease Pregnancy Chronic renal failure Lymphoma and other malignancies Congestive heart failure Infection and inflammation
Infiltrating diseases of liver causing elevation in alk phos
Sarcoidosis Tuberculosis Fungal infection Other granulomatous diseases Amyloidosis Lymphoma Metastatic malignancy Hepatocellular carcinoma
elevated Alk phos algorithm
H&P liver chem normal AST and ALT? gamaGGT or 5'nucleotidase (if elevated move to RUQ US below) normal? etiology is not hepatobiliary
Abnormal AST and ALT? RUQ US to assess for biliary duct dilatation yes: ERCP or MRCP No: AMA: Positive? PBC Negative?*Evaluation for elevated ALT, liver biopsy and/or ERCP or MRCP (ie eval for
Bilirubin
Normal heme degradation product
Excreted from body via secretion into bile
Insoluble in water
Requires conjugation (glucuronidation) into water-soluble forms before biliary excretion
- Unconjugated (indirect) bilirubin
- Conjugated (direct) bilirubin
Location of conj/unconj bili
unconjugated bili in blood to liver (ER), conjugated, and put in bile canaliculus
Biliary obstruction and bilirubin
can’t get conjugate bili out, ends up back in blood: increased conjugated bilirubin
Gilbert’s disease
decreased bilirubin uptake
Most common inherited disorder of bilirubin glucuronidation
Mutation in promoter region of gene encoding for UDP-GT resulting in reduced activity
5-10% Western population homozygous for condition
Conditions associated with elevated bilirubin Hemolysis Fasting Febrile illness Physical stress
delay in moving unconjugated bilirubin to liver (elevated total bili)
Crigler-Najjar Syndrome
impaired bilirubin conjugation
Rare, autosomal recessive
UDP-GT deficiency or low levels of enzyme
Type I: severe jaundice, neurologic impairment
Type II: lower serum bilirubin, no neurologic impairment
Dubin-Johnson syndrome*
defective secretion of conjugated bilirubin
rare Impairment of biliary excretion Mutation of MRP-2 gene Protein responsible for transporting conjugated bilirubin from hepatocyte into bile canaliculus Most defects in ATP binding region Benign, no Rx needed
bili and cirrhosis
- RBC membranes less stable
- RBC removed more frequently (so increased unconjugated bili)
- scarring: hard to get bili in and out
- reduced liver mass (Scar tissue)
Hard to process
Classification of cholestasis (decreased bile flow
site of lesion: canaliculus or biliary ductules
detection: lab tests or liver biopsy
common ex: cholestatic drugs rxns, PBC preg
site: intra/extrahepatic bile ducts
Detectin: imaging: US ERCP MRCP
ex: Biliary atresia, PSC, gallstones, malignancy of pancreas or bile duct
unconj (indir) hyperbili
Gilbert’s syndrome
Hemolysis (increased heme breakdown)
Crigler-Najjar syndrome
conjugated (direct) hyperbili
Extrahepatic obstruction of bile flow
Intrahepatic cholestasis
Hepatitis
Cirrhosis
elevated bili algorithm
H&P, liver chem
unconj bili, nml AST & ALT and alk phos:
Gilbert’s syndrome, hemolysis studies
or
Conjugated bili, abnorm AST and ALT and alk phos:
RUQ US to assess for ductal dilatation
Present: ERCP or MRCP
Absent: Elevated ALT evaluation, AMA, ERCP or MRCP and/or liver biopsy
Common Liver chem tests and implications of abnormality
AST: hepatocell damage
ALT: hepatocell damage
Bilirubin: cholestasis, impaired conjugation, or biliary obstruction
Alk phos: cholestasis, infiltrative disease, or biliary obstruction
Albumin: synthetic dysfunction
–
PTT: synthetic dysfunc
PAtterns of liver chem abnormalities
predom AST/ALT elev: hepatocellular injury or necrosis
Cholestatic pattern: predom alk phos elev
Look up bili metabolism and review handout**
–
Reasons to treat chronic hepatitis
Prevent liver failure and development of cirrhosis and associated complications:
Varices
Ascites
Hepatic encephalopathy
Reduce risk of hepatocellular carcinoma
HBsAg
hep B surface antigen:
marker of active infection
presence for>6 mo defines chronic hep B infection
HBsAB
(or anti-HBs)
antibody to HBsAG
-marker of immunity to hepatitis B
HBcAB
hep B core antibody
-marker of active or prior infection
(can’t tell if chronic or new)
HBeAg
hep B “e” antigen
-marker of high viral load
HBeAB (or anti-Hbe)
antibody to hep B “e” antigen
HBV DNA
presence means active viral replication
Goal of HBV treatment
HBeAg seroconversion:
Loss of HBeAg and development of HBeAb associated with negative HBV DNA when treatment stopped
Prevention of decompensated cirrhosis in those with advanced fibrosis
Note: Loss of HBsAg rarely occurs
Chronic HBV infection indications for tx
- HBsAg(+) > 6 months*
- Serum HBV DNA >105 copies/mL
- Persistent or intermittent elevation in ALT and AST levels
- Liklihood of HBeAg seroconversion with normal ALT is very low
-treat pts w/ advanced liver disease
Treatment options for HBV
Interferon
- Finite duration of therapy (1 year)
- Absence of resistant mutations
- More durable response
- feel like you have flu
Nucleoside/tide analoges
Fewer side effects
Resistant mutations
(people choose this option)
If undergo tx for HBV, and still have HBs Ag… risk of
liver cancer still.
tx prevented virus replication, but you still technically have hepatitis B
Look at cases 10/27 8a
–
chronic HCV and goal of tx
defined as presence of HCV RNA in blood >6mo after infection
Goal of antiviral therapy is to clear HCV RNA: HCV RNA negative 12 weeks after stopping therapy
Sustained virological response (SVR) = cure
(HCV antibody often positive, but definition of infection is HCV RNA >6mo)
tx of HCV
Tx: pills, but very expensive ($1,000/d)
Hereditary hemochromatosis
Inherited disorder: increased intestinal iron absorption
Consider w/ elevated AST and ALT
Tx: therapeutic phlebotomy:
500 mL of whole blood = 200-250 mg iron
Endpoint is serum ferritin 50 ng/mL
Maintenance phlebotomy to keep ferritin 50-100 ng/mL
For anemic patients not able to tolerate phlebotomy, chelation therapy with desfuroxamine
Gene: C282Y
look at case!
Autoimmune hepatitis
Chronic hepatitis characterized by immunologic and autoimmune features
Treatment based on immune suppression:
Corticosteroids
Azathioprine
Relapse typically occurs if treatment stopped after liver enzymes normalized
50% chance of flair with cessation of therapy 2 year after achieving remission
Often see plasma cells on histology, bridging necrosis, etc.
***Primary biliary cirrhosis
Immune mediated disease causing damage to SMALL (micro) intrahepatic bile ducts
Tx: ursodeoxycolic acid (UDCA):
Secondary bile acid, metabolic byproduct of intestinal bacteria
Improves bile acid transport, “detoxifies” bile and providing cytoprotection
Use of UDCA:
Improved liver biochemistries
Improve survival
Reduce need for liver transplantation
Alk phos more elevated than ALT
Dx: antimitochondrial Ab
Check DEXA for osteoporosis
PSC
Inflammatory disease of the intra- and extrahepatic LARGE bile ducts
Leads to strictures and obstruction of bile ducts and can ultimately result in cirrhosis
No effective medical therapy
Treatment focused on management of complications of bile duct obstruction:
- Stenting strictures
- Antibiotics for cholangitis
Risk for cholangiocarcinoma
Most with this have UC (20% w/ UC have this)
Wilson Disease
AR
Decreased hepatocullar copper excretion –> hepatic copper accumulation and injury
Tx: copper chelation:
D-penicillamine
Trientine
Maintenance therapy with zinc
Might see Kayser-Fleisher rings (Cu rings around iris)
Non-alcoholic steatohepatitis
NASH is presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning with or without fibrosis) Tx: modifying risk factors -Obesity -Diabetes mellitus type 2 -Dyslipidemia
Investigational therapies
Diabetes medications – even if not diabetic
Vitamin E - antioxidant
no real effective tx currently
