Download Liver function tests: Hepatic

LIVER FUNCTION TESTS:
HEPATIC
Megan Chan, PGY-1
UHCMC 2015
LIVER FUNCTION
 Bile synthesis & secretion
 Bilirubin production and
excretion
 Detoxification: e.g. converts
ammonia into urea
• “First pass metabolism”
• Phase 1 reaction via cytochrome
P450 enzymes
• Phase 2 reaction—conjugation
of substances
• Kupffer cells—liver
macrophages
 Metabolic function
• Gluconeogenesis, glycogen
storage
• Synthesis of plasma proteins,
albumin, clotting factors, nonessential amino acids
• Fatty acid oxidation, synthesis of
cholesterol, lipoproteins
LIVER ANATOMY
 Afferent vessels
• Hepatic artery—30% of blood flow, oxygenated
• Portal vein—70% of blood flow
 Efferent vessels
• Bile duct
• Central vein (aka Terminal hepatic vein)
 Portal Triad
• Bile duct + Hepatic artery + Portal vein
http://studydroid.com/imageCards/0a/k1/card-11143124-back.jpg
BILIRUBIN
First Aid for USMLE Step 1
GUESS THE LFTS
ACUTE HEPATITIS
 AST
• Elevated
 ALT
• Elevated
 Alk Phos
• Normal
 T bili
• Normal
http://www.atsu.edu/faculty/chamberlain/Website/lectures/lecture/hepatit
2.htm
CIRRHOSIS
 AST
• Normal/Elevated
 ALT
• Normal/Elevated
 Alk Phos
• Normal/Elevated
 T bili
• Normal/Elevated
http://hepatitiscnewdrugresearch.com/evaluation-staging-andmonitoring-of-chronic-hepatitis-c.html
CIRRHOSIS
 As cirrhosis progresses, Total Bili increases because the liver can
still conjugate bilirubin but can’t excrete it.
 MELD Score for 3 month mortality:
•
•
•
•
Total bilirubin
Serum creatinine
INR
± Dialysis
40 + --71.3% mortality
30-39– 52.6% mortality
20-29– 19.6% mortality
10-19 – 6.0% mortality
<9 – 1.9% mortality
CHILD PUGH SCORE
 Classification to assess severity of liver disease & hepatic functional reserve
Points
1
2
3
Ascites
None
Controlled
Uncontrolled
Bilirubin
<2.0
2.0-3.0
>3.0
Encephalopathy
None
Minimal
Severe
INR
<1.7
1.7-2.2
>2.2
Albumin
>3.5
2.8-3.5
<32.8
Classification
A
B
C
Total points
5-6
7-9
10-15
1-yr survival
100%
81%
45%
2-yr survival
85%
57%
35%
LIVER TRANSPLANT
 Evaluate when Child Class B or MELD ≥ 10
 Indications:
•
•
•
•
•
•
•
Recurrent/severe encephalopathy
Refractory ascites
SBP
Recurrent variceal bleeding
Hepatorenal or Hepatopulmonary syndrome
HCC if no single lesion > 5cm or ≤ 3 lesions w/ largest ≤ 3 cm
Fulminant hepatic failure
 Contraindications:
• Advanced HIV, active substance abuse (ETOH w/in 6 mo), sepsis,
extrahepatic malignancy, severe comorbidity (esp cardiopulm), persistent
non-compliance
PRACTICE CASES
CASE 1
65 y/o male with 25 year history of alcohol and tobacco abuse who presents
with abdominal swelling and confusion. Pt reports an unintentional 15 lbs
weight gain and frequent forgetfulness. On exam, pt is A&O x1 (only to
person), is slow to answer questions and often answers inappropriately. Pt
has scleral icterus, distended abdomen with + fluid wave, and several
ecchymoses on his lower extremities. Slight asterixis is observed.
What is the most likely diagnosis?
CASE 1
65 y/o male with 25 year history of alcohol and tobacco abuse who presents with
abdominal swelling and confusion. Pt reports an unintentional 15 lbs weight gain
and frequent forgetfulness. On exam, pt is A&O x1 (only to person), is slow to
answer questions and often answers inappropriately. Pt has scleral icterus,
distended abdomen with + fluid wave, and several ecchymoses on his lower
extremities. Slight asterixis is observed.
What is the most likely diagnosis?
Alcoholic Cirrhosis
EARLY/LATE CIRRHOSIS
http://radiopaedia.org/cases/cirrhosis
HISTOLOGY
 Focal hepatocellular necrosis with 3 characteristics:
• Fibrosis
• Nodular regeneration
• Distortion of hepatic architecture
http://tissupath.co
m.au/educationmedical-studentliver/
http://medchrome.com/basic-science/pathology/morphologyalcoholic-liver-disease/
“LIVER STAMP”








Liver US with dopplers (for portal vein thrombosis)
ANA, Anti smooth muscle Ab (autoimmune)
Anti-mitochondrial Ab (primary biliary cirrhosis)
Ceruloplasmin (Wilson’s)
Ferritin + Iron studies w/ TIBC (Hemochromatosis)
HepBs Ag, HepBs Ab, HepBc Ab
HepC Ab, HepC PCR
Alpha-antitrypsin
“LIVER STAMP”
AVERAGE COST?
~$1,200
CIRRHOSIS ETIOLOGY
 Fatty liver diseases
• Alcoholic liver disease
• NASH/NAFLD
 Viral hepatitis: Hep B, C, D
 Autoimmune
• Autoimune hepatitis
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
 Cardiovascular
• Budd-Chiari syndrome
• Chronic right heart failure
 Chronic biliary disease
• Recurrent bacterial cholangitis
• Bile duct stenosis
 Storage diseases
• Hemochromatosis
• Wilson disease
• α-1-antitrypsin deficiency
 Meds: APAP toxicity, MTX
 Cryptogenic 10-15%
DIAGNOSTIC IMAGING
 Ultrasound
• Surface nodularity: 88% sensitive, 82-95% specific (1)
• Coarse & heterogeneous echotexture
• Signs of portal HTN:
• Portal vein >13mm: 42% sensitive, 95-100% specific (2)
• Splenomegaly, ascites
 CT insensitive in early cirrhosis
 MRI also insensitive in early cirrhosis, but significant role in
assessing small hepatocellular carcinoma (HCC)—develops in 10-25%
 Liver biopsy = gold standard for diagnosis
TREATMENT
 Ascites
•
Furosemide + Spironolactone with goal negative ~1L/day (~80% effective)
•
•
Lasix: Aldactone ratio of 2:5 helps maintain K+ (thus Lasix 40mg qday, Aldactone 100mg qday initially)
Low-sodium diet (1-2 g/day)
 Refractory Ascites= no response on max doses of Lasix (160mg) & Aldactone (400mg)
•
LVP 4-6L (does not improve mortality)
•
•
•
Albumin replacement controversial. AASLD 2009 guidelines recommend if >5L removed, provide 6-8
g/L of albumin 25% (IIA, Grade C)
If >5L removed, can have post-paracentesis circulatory dysfxn via RAAS activation
TIPS (↓ ascites in 75%, improves mortality but ↑ HE, 40% need revision for stent stenosis)
 Hepatic encephalopathy
•
Lactulose
 Hepatorenal syndrome
•
Transplantation
CASE 2
57 y/o known HepC cirrhotic presents with malaise, fevers and chills. Her
husband reports she has been intermittently confused over the past few
days despite taking her lactulose. Exam shows significant ascites and
diffuse abdominal tenderness to palpation. Diagnostic paracentesis reveals:
straw-colored fluid with pH < 7.3, WBC 1000 with 70% PMNs, glucose 35,
total protein 30. SAAG is calculated to be 1.5.
What is the most likely diagnosis?
CASE 2
57 y/o known HepC cirrhotic presents with malaise, fevers and chills. Her
husband reports she has been intermittently confused over the past few days
despite taking her lactulose. Exam shows significant ascites and diffuse
abdominal tenderness to palpation. Diagnostic paracentesis reveals: strawcolored fluid with pH < 7.3, WBC 1000 with 70% PMNs, glucose 35, total
protein 30. SAAG is calculated to be 1.5.
What is the most likely diagnosis?
Spontaneous Bacterial Peritonitis (SBP)
SBP
 Develops in ~20% cirrhotics, ~10-25% asymptomatic, ~20% mortality
 Risk factors:
• AFTP < 1 g/dL, current GIB, hx of SBP, Lines/catheters, Childs C
cirrhosis, fulminant hepatic failure
 Culture can be negative in 30-50%, Gram stain + in only 5-10%
 70% is GNR (E.coli, Klebs), 30% GPC (S. pneumo, Enterococcus)
SBP
 Treatment
• Cefotaxime 2gm IV q8hrs x 5 days, Norfloxacin PO in uncomplicated
SBP
• IV albumin 1.5g/kg at time of dx then 1g/kg on day 3 (↑ survival and ↓
renal impairment)
 If no improvement, repeat para at 48 hrs (~25% ↓ PMN count = tx
success)
 Prophylaxis
• GI bleeds: Norfloxacin 400mg PO q12 hrs
• Hx of SBP: Norfloxacin400mg qd, Cipro 750mg qwk, Bactrim DS qd (↓ 1
yr recurrence from 70% to 20%, ↑ survival)
http://medicine.ucsf.edu/education/resed/Chiefs_cover_sheets/SBP,%20cirrhosis,%20empyema.pdf
ASCITES:
PATHOPHYSIOLOGY
Also:
1. Hypoalbuminemia  ↓
serum oncotic pressure
2. ↑ hepatic lymph  ↑
splanchnic pressure
http://medical-dictionary.thefreedictionary.com/ascites
PARACENTESIS
 What tests would you send?
• 4 C’s: Cells, Culture, Chemistry, Cytology
• Cell count and differential, gram stain, culture, albumin, total protein,
glucose, LDH, cytology
• Optional: amylase, bilirubin, Cr, TG, AFB cx + adenosine deaminase
 How do you calculate the SAAG?
• SAAG = [Serum albumin] – [Ascites albumin]
 What does the SAAG indicate?
• If ≥ 1.1 g/dL, portal HTN is very likely (~97% accurate1)
• If < 1.1 g/dL, portal HTN is unlikely.
Runyon et al. “The serum-ascites albumin gradient is superior to the exudates-transudate concept in the differential diagnosis of ascites.”
Annals of Internal Medicine 1992; 117:215-20.
PARACENTESIS
SAAG ≥ 1.1
 Sinusoidal
• Cirrhosis(81%), SBP
• Acute hepatisis
• Extensive malignancy
(HCC/mets, 10%)
 Postsinusoidal
• R heart failure (3%)
• Budd-Chiari Syndrome
 Presinusoidal
• Portal/splenic vein
thrombosis
SAAG < 1.1
 Peritonitis: TB, ruptured viscus
 Peritoneal carcinomatosis
 Pancreatitis
 Vasculitis
 Hypoalbuminemia (e.g. nephrotic
syndrome)
 Meigs’ syndrome (ovarian tumor)
 Bowel obstruction/infarction
 Post-op lymphatic leak
Runyon et al. “The serum-ascites albumin gradient is superior to the exudatestransudate concept in the differential diagnosis of ascites.” Annals of Internal
Medicine 1992; 117:215-20.
PARACENTESIS
 Ascites fluid total protein (AFTP) useful when SAAG ≥ 1.1









• Cirrhosis (AFTP < 2.5) vs Cardiac ascites (AFTP > 2.5)
Bloody fluid: 50% with HCC, 22% with malignancy
For traumatic taps, subtract 1 PMN for every 250 RBC.
Cell count: PMN ≥ 250 cells/μL = SBP (93% sensitivity, 94% specificity)
Total protein < 1 g/dL  high risk for SBP
Glucose: ↓ in infection and malignancy
LDH: ↑ in infection and malignancy
Amylase (fluid/serum ratio > 0.4): pancreatitis, gut perforation
TG: > 1000 in chylous ascites
Cytology overall sensitivity 58-75%
• However 100% sensitive in peritoneal carcinomatosis (~2/3 of malignantrelated ascites)
Runyon et al. “The serum-ascites albumin gradient is superior to the exudates-transudate concept in the differential diagnosis of ascites.”
Annals of Internal Medicine 1992; 117:215-20.
BACTERIAL PERITONITIS
Type
Ascites Cell
Count
Ascites Culture
Sterile
< 250 PMNs
Neg
Spontaneous bacterial peritonitis (SBP)
≥ 250 PMNs
+ (1 organism)
Culture neg neutrocytic ascites (CNNA)
≥ 250 PMNs
Neg
Nonneutrocytic bacterascites (NNBA)
< 250 PMNs
+ (1 organism)
Secondary
≥ 250 PMNs
+ (polymicrobial)
≥ 100, PMNs predom
+
Peritoneal dialysis-associated
CASE 3
35 y/o male presents with fatigue and tea-colored urine for 5 days. Exam
reveals jaundice and tender heaptomegaly but is otherwise unremarkable.
Labs are significant for AST 2400, ALT 2640, Alk Phos 210, and Total
Bilirubin 8.6.
Which of the following is least likely to cause this clinical picture?
A. Acute hepatitis A infection
B. Acute hepatitis B infection
C. Acute hepatitis C infection
D. Acetaminophen ingestion
E. Budd-Chiari Syndrome
CASE 3
Which of the following is least likely to cause this clinical picture?
A. Acute hepatitis A infection
B. Acute hepatitis B infection
C. Acute hepatitis C infection
D. Acetaminophen ingestion
E. Budd-Chiari Syndrome
Extreme elevations in transaminases usually fall into 3 major categories:
viral infections, toxic ingestions, and vascular/hemodynamic causes
(shock liver). Hep C does not typically cause acute infection.
CASE 4
24 y/o patient is admitted to the MICU with obtundation and jaundice
over 1-2 days. No further history is available. The following labs are
obtained:
Total Bili 7.2, Direct Bili 4.0, AST 1478, ALT 1056, Alk Phos 132, INR
3.1, Albumin 3.6.
All of the following tests are indicated except?
A. Antinuclear Ab (ANA)
B. Ceruloplasmin
C. Hepatitis B surface Ag
D. ERCP
E. Toxicology screen
CASE 4
All of the following tests are indicated except?
A. Antinuclear Ab (ANA)
B. Ceruloplasmin
C. Hepatitis B surface Ag
D. ERCP
E. Toxicology screen
When evaluating a patient with jaundice, initial steps include determining
whether the hyperbilirubinemia is predominantly unconjugated or conjugated
and whether there is any other evidence for hepatobiliary dysfxn. Next is to
discriminate into a predominantly cholestatic or hepatocellular pattern. In this
case, the pt has a hepatocellular pattern with AST/ALT elevated out of
proportion to Alk Phos.
Harrison’s
Internal Medicine
CASE 5
41 y/o male who presents to your clinic with a week of jaundice. He notes
pruritus, icterus, and dark urine. He denies fever or abdominal pain. Exam is
unremarkable except for jaundice.
Labs: Total bili 6.0 , direct bili 5.1, AST 84 , ALT 92, Alk phos 662.
CT scan of abdomen is unremarkable. RUQ ultrasound shows a normal bile
duct but does not visualize the common bile duct.
What is the most appropriate next management step?
A. Antibiotics and observation
B. ERCP
C. Hepatic serologies
D. HIDA scan
E. Serologies for antimitochondrial Ab
CASE 5
What is the most appropriate next management step?
A. Antibiotics and observation
B. ERCP
C. Hepatic serologies
D. HIDA scan
E. Serologies for antimitochondrial Ab
Anatomic abnormalities are more common when there is a cholestatic pattern of
injury (Alk Phos elevated out of proportion to AST/ALT). Painless jaundice
always requires extensive workup with concern for malignant causes (e.g.
cholangiocarcinoma, tumor of ampulla of vater) vs nonmalignant causes (e.g.
primary sclerosing cholangitis), which may only be detected by direct visualization
with ERCP. Negative CT does not rule out source of cholestatis in biliary tree.
Furthermore, ERCP is useful therapeutically with stenting to alleviate the
obstruction.
Harrison’s
Internal Medicine
CASE 6
61 y/o male is admitted to your service for new onset ascites. You
perform a paracentesis with the following results of the non-bloody
peritoneal fluid:
WBC 300 with 35% PMNs, albumin 1.2, protein 2.6, TG 320
Peritoneal cultures are pending. Serum albumin 2.7.
Which of the following is the most likely diagnosis?
A. Peritoneal tuberculosis
B. Peritoneal carcinomatosis
C. Congestive heart failure
D. Bacterial peritonitis
E. Chylous ascites
CASE 6
Which of the following is the most likely diagnosis?
A. Peritoneal tuberculosis
B. Peritoneal carcinomatosis
C. Congestive heart failure
D. Bacterial peritonitis
E. Chylous ascites
SAAG 1.5, AFTP 2.6  Cardiac ascites
Low WBC and PMNs make SBP and TB less likely
CASE 7
An alcoholic cirrhosis patient has increasing ascites despite dietary sodium control and
diuretics. A paracentesis shows clear, turbid fluid. There are 2300 WBCs and 150 RBC.
Differential shows 75% lymphocytes. Fluid protein is 3.2 and SAAG is 1.0.
What is the most appropriate next test?
A. Adenosine deaminase activity of ascitic fluid
B. CT scan of liver
C. Peritoneal biopsy
D. None; consider transplant evaluation
CASE 7
What is the most appropriate next test?
A. Adenosine deaminase activity of ascitic fluid
B. CT scan of liver
C. Peritoneal biopsy
D. None; consider transplant evaluation
In pts with chronic cirrhosis who develop new or worsening ascites without dietary
or medication nonadherence, consider an occult disorder (e.g. peritoneal TB, HCC,
portal vein thrombosis). ↑ WBC is more common in neoplasm, bacterial peritonitis,
or TB. Predominance of lymphocytes raises the suspicion for TB. SAAG is
classically low in TB peritonitis but can be elevated in concomitant
cirrhosis/transudative ascites. The sensitivity of ADA is poor in those with
cirrhosis 2/2 poor T cell-mediated response. Thus peritoneal biopsy or visual
diagnosis during laparoscopy is likely needed to confirm the diagnosis.
PARACENTESIS
SAAG ≥ 1.1
 Sinusoidal
• Cirrhosis(81%), SBP
• Acute hepatisis
• Extensive malignancy
(HCC/mets, 10%)
 Postsinusoidal
• R heart failure (3%)
• Budd-Chiari Syndrome
 Presinusoidal
• Portal/splenic vein
thrombosis
SAAG < 1.1
 Peritonitis: TB, ruptured viscus
 Peritoneal carcinomatosis
 Pancreatitis
 Vasculitis
 Hypoalbuminemia (e.g. nephrotic
syndrome)
 Meigs’ syndrome (ovarian tumor)
 Bowel obstruction/infarction
 Post-op lymphatic leak
Runyon et al. “The serum-ascites albumin gradient is superior to the exudatestransudate concept in the differential diagnosis of ascites.” Annals of Internal
Medicine 1992; 117:215-20.
WHEN TO TAP/RETAP
 New ascites
 Admission of all patients with cirrhotic ascites
 Deterioration in clinical status
 Complication of cirrhosis (GI bleed, confusion)
 Polymicrobial culture or + culture with PMN < 250 (MNB that may be
early SBP)
 Retap 24-48 hrs after treatment started in pts with PMN> 1000
(associated with 88% mortality) or lack of improvement.
http://medicine.ucsf.edu/education/resed/Chiefs_cover_sheets/SBP,%20cirrhosis,%20empyema.pdf
CASE 8
When evaluating a patient with chronic ascites, a SAAG > 1.1 is
consistent with all of the following diagnoses except?
A. Cirrhosis
B. Congestive heart failure
C. Constrictive pericarditis
D. Hepatic vein thrombosis
E. Nephrosis
CASE 8
When evaluating a patient with chronic ascites, a SAAG > 1.1 is
consistent with all of the following diagnoses except?
A. Cirrhosis
B. Congestive heart failure
C. Constrictive pericarditis
D. Hepatic vein thrombosis
E. Nephrosis
PARACENTESIS
SAAG ≥ 1.1
 Sinusoidal
• Cirrhosis(81%), SBP
• Acute hepatisis
• Extensive malignancy
(HCC/mets, 10%)
 Postsinusoidal
• R heart failure (3%)
• Budd-Chiari Syndrome
 Presinusoidal
• Portal/splenic vein
thrombosis
SAAG < 1.1
 Peritonitis: TB, ruptured viscus
 Peritoneal carcinomatosis
 Pancreatitis
 Vasculitis
 Hypoalbuminemia (e.g. nephrotic
syndrome)
 Meigs’ syndrome (ovarian tumor)
 Bowel obstruction/infarction
 Post-op lymphatic leak
Runyon et al. “The serum-ascites albumin gradient is superior to the exudatestransudate concept in the differential diagnosis of ascites.” Annals of Internal
Medicine 1992; 117:215-20.
http://image.slidesharecdn.com/complicationsofcirrhosis-100914093820-phpapp02/95/complications-of-cirrhosis-18-728.jpg?cb=1284460955
CASE 9
28 y/o woman who is 30 weeks pregnant presents with 2 week history
of pruritus and scleral icterus. It is her first pregnancy, and she has
no significant medical hx. She does not drink alcohol and takes only a
prenatal vitamin. Vitals are stable. Exam reveals a gravid uterus, mild
scleral icterus and linear excoriations on the skin. There is no ascites
or lower extremity edema.
CASE 9
Labs reveal:
Hb 13.4 Platelet 275.000
AST 44, ALT 38, Total Bili 4.2, Direct Bili 2.3, Alk Phos 180
LDH 82, INR 1.0
Hep Bs Ag Neg, Hep Bs Ab Positive,
Hep C Ab Neg, Hep A Ab (IgG) Positive
ANA negative, Anti-smooth muscle Ab neg
Ultrasound of the liver is normal.
CASE 9
Which of the following is the most likely diagnosis?
A. Acute fatty liver of pregnancy
B. Acute hepatitis A infection
C. Cholestasis of pregnancy
D. HELLP syndrome
CASE 9
Which of the following is the most likely diagnosis?
A. Acute fatty liver of pregnancy
B. Acute hepatitis A infection
C. Cholestasis of pregnancy
D. HELLP syndrome
Cholestasis of pregnancy is the most common pregnancy-related liver disorder that is benign
for the mother but increases risk for pre-term delivery and fetal loss if untreated. It often
presents in the 2nd or 3rd trimester of pregnancy and treatment is with ursodeoxycholic acid
for symptomatic treatment.
In contrast acute fatty liver occurs in the 3rd trimester and is associated with high AST/ALT,
high bilirubin and fat on liver US.
HELLP syndrome is part of spectrum of eclampsia/pre-eclampsia and presents with HTN,
hemolytic anemia, proteinuria high AST/ALT, & thrombocytopenia. It occurs during 3rd
trimester and up to 48 hrs postpartum. Tx is delivery of the baby.
CASE 10
45y/o male admitted for 2 day hx of fever and abdominal pain. Medical hx is
notable for HepC cirrhosis and esophageal varices. Medications include
furosemide, spironolactone, nadolol, and lactulose. Pt is afebrile, BP 100/50, HR
84. Abdominal exam is consistent with ascites and is nontender to palpation.
Labs: Hb 10, WBC 3500, Plt 70,000, INR 1.5, Albumin 2.5, Alk Phos 220, AST
40, ALT 30, T bili 4, Cr 1.8, UA normal.
Abdominal US shows cirrhosis, spenomegaly, & ascites. Portal & hepatic veins are
patent. Diagnostic paracentesis shows WBC 2000 with 20% PMNs, Total protein
1, Albumin 0.7.
Which of the following is the most appropriate treatment?
A. Cefotaxime
B. Cefotaxime and albumin
C. Furosemide and spironolactone
D. LVP
E. Observation
CASE 10
Which of the following is the most appropriate treatment?
A. Cefotaxime
B. Cefotaxime and albumin
C. Furosemide and spironolactone
D. LVP
E. Observation
In patients with SBP, the concomitant use of IV albumin with antibiotic
therapy is associated with a survival benefit compared with antibiotic therapy
alone.
REFERENCES
 Adamek HE, Albert J, Weitz M et-al. A prospective evaluation of magnetic resonance cholangiopancreatography in
patients with suspected bile duct obstruction. Gut. 1998;43 (5): 680-3.
 Agabegi SS, Agabegi ED. Step –Up to Medicine, 3rd ed. 2013. Lippincott Williams & Wilkins. Philadelphia, PA.
 Caoili EM, Paulson EK, Heyneman LE et-al. Helical CT cholangiography with three-dimensional volume rendering
using an oral biliary contrast agent: feasibility of a novel technique. AJR Am J Roentgenol. 2000;174 (2): 487-92.
 Cronan JJ. US diagnosis of choledocholithiasis: a reappraisal. Radiology. 1986;161 (1): 133-4.
 Guardino JM. Primo Gastro. 2008. Lippincott Williams & Wilkins. Philadelphia, PA.
 Miller FH, Hwang CM, Gabriel H et-al. Contrast-enhanced helical CT of choledocholithiasis. AJR Am J Roentgenol.
2003;181 (1): 125-30.
 Sabatine, MS. Pocket Medicine, 4th ed. 2011. Lippincott Williams & Wilkins. Philadelphia, PA.
 Sugiyama M, Suzuki Y, Abe N et-al. Endoscopic retreatment of recurrent choledocholithiasis after sphincterotomy.
Gut. 2004;53 (12): 1856-9.
 Wiener C, Fauci AS, Braunwald E, et al. Harrison’s Principles of Internal Medicine Self-Assessment & Board Review,
17th ed. 2008. McGraw Hill. New York, NY.
 http://medicine.ucsf.edu/education/resed/Chiefs_cover_sheets/SBP,%20cirrhosis,%20empyema.pdf
 http://radiopaedia.org
 Special thanks to Dr. Caroline Soyka for the inspiration!