LIVER FUNCTION TESTS:
BILIARY
Megan Chan, PGY-1
UHCMC 2015
GUESS THE LFTS
CHOLELITHIASIS
If Asymptomatic:
If Pass a Stone:
 AST
 AST
• Normal
 ALT
• Normal
 Alk Phos
• Normal
 T bili
• Normal
• Elevated
 ALT
• Elevated
 Alk Phos
• Elevated
 T bili
• Normal
http://radiopaedia.org/articles/cholelithiasis
ACUTE CHOLECYSTITIS
 AST
• Normal
 ALT
• Normal
http://radiopae
dia.org/images/
1780983
 Alk Phos
• Elevated
 T bili
• Normal
http://radiopaedia.or
g/cases/acutecholecystitis-4
CHOLEDOCHOLITHIASIS
 AST
• Normal  Elevated
 ALT
• Normal  Elevated
 Alk Phos
• Elevated
 T bili
• Elevated
http://radiopaedia.org/articles/choledocholithiasis
PRACTICE CASES
CASE 1
46 y/o female presents with
intermittent RUQ pain and
heartburn to your clinic. Vitals
are stable and exam is
unremarkable. CT abdomen
from an OSH is shown on the
right.
What is the diagnosis?
http://radiopaedia.org/articles/cholelithiasis
CASE 1
46 y/o female presents with
intermittent RUQ pain and
heartburn to your clinic. Vitals
are stable and exam is
unremarkable. CT abdomen
from on OSH is shown on the
right.
What is the diagnosis?
Cholelithiasis
http://radiopaedia.org/articles/cholelithiasis
CHOLELITHIASIS
 Gallstones or sludge in the gallbladder
 ~10% population, symptomatic in only 25% of cases
 3 types of stones:
• Cholesterol stones—associated with obesity, DM, HLD, OCP use, multiple
pregnancies, advanced age, Crohn’s disease, ileal resection, cirrhosis, CF
• Pigment stones
•
•
Black stones—hemolysis, alcoholic cirrhosis
Brown stones—biliary tract infection
• Mixed stones = 80%
 Pathophysiology:
• Cholesterol supersaturation from reduced bile secretion (age, TI disease, liver dz) or
hypersecretion of cholesterol (e.g. estrogen, obesity liver dz)
• Crystal nucleation
• Gallbladder hypomotility (e.g. pregnancy, prolonged TPN, somatostatin)
• Other: Decreased bile transit time, bacteria presence
CHOLELITHIASIS
 Clinical features:
• Biliary colic, esp after eating & at night, lasts 30 min to 3 hrs
• Boas’ sign = referred right subscapular pain of biliary colic
 Diagnosis: RUQ ultrasound has sensitivity and specificity >
95% for stones > 2mm, best if fasting ≥ 8 hrs
 Tx: Elective cholecystectomy for pts with recurrent biliary colic
 DDx: Gallbladder polyp/carcinoma
CASE 2
55 y/o male with PMHx of recurrent pancreatitis presents to the ED
with RUQ abdominal pain and vomiting. Pt is found to be febrile and
hypotensive. IV fluids are initiated and the following labs are obtained:
WBC 13,000, AST 25, ALT 30, Alk Phos 450, T bili 1.0, Lipase 20
What is the most likely diagnosis and what is the next best
diagnostic step?
CASE 2
55 y/o male with PMHx of recurrent pancreatitis presents to the ED with
RUQ abdominal pain and vomiting. Pt is found to be febrile and
hypotensive. IV fluids are initiated and the following labs are obtained:
WBC 13,000, AST 25, ALT 30, Alk Phos 450, T bili 1.0, Lipase 20
What is the most likely diagnosis and what is the next best diagnostic
step?
Acute Cholecystitis, RUQ ultrasound
ACUTE CHOLECYSTITIS
 Inflammation of gallbladder 2/2 obstruction of cystic duct
 Develops in 10% of those with cholelithiasis
 Clinical features:
• RUQ tenderness >4-6 hrs ± rebound
• Murphy’s sign = inspiratory arrest during deep palpation of RUQ
• Low grade fever, leukocytosis, nausea, vomiting, hypoactive bs
ACUTE CHOLECYSTITIS
 Diagnosis:
• US is test of choice
• Distended gallbladder with thickened wall > 5mm,
pericholecystic fluid, ± stones
• HIDA radionuclide scan if US inconclusive
• If gallbladder not visualized 4 hours after injection, diagnosis
is confirmed.(97% sensitive, 96% specific)
 Treatment:
• Supportive: IV fluids, NPO, IV abx (Zosyn, Unasyn, 3rd gen
cephalasporin + Flagyl), analgesics, electrolyte replacement
• Semiurgent Cholecystectomy w/in 72 hrs to avoid
gangrenous/emphysematous cholecystitis
http://www.stritch.luc.edu/l
umen/MedEd/Radio/curric
ulum/Procedures/HIDA_sc
an1.htm
CASE 3
52 y/o male transferred from an OSH for intermittent abdominal pain
and progressive jaundice over the past 2 days. Further history reveals
symptoms consistent with biliary colic. Exam shows a patient in mild
distress with tenderness in the RUQ and jaundice. Labs are significant
for: AST 450, ALT 520, Alk Phos 630, T Bili 4.2
What is the most likely diagnosis and what is your next step in
management?
CASE 3
52 y/o male transferred from an OSH for intermittent abdominal pain and
progressive jaundice over the past 2 days. Further history reveals symptoms
consistent with biliary colic. Exam shows a patient in mild distress with
tenderness in the RUQ and jaundice. Labs are significant for: AST 450, ALT
520, Alk Phos 630, T Bili 4.2
What is the most likely diagnosis and what is your next step in
management?
Choledocholithiasis, ERCP—diagnostic and therapeutic
CHOLEDOCHOLITHIASIS
 Gallstones within the common bile duct or common hepatic
duct, formed in situ or passed from gallbladder
 Presentation: asymptomatic (~50%) biliary colic  ascending
cholangitis, obstructive jaundice, acute pancreatitis
 Definitions of dilated bile duct
• >6mm + 1mm per decade above 60 y/o
• >10 post-cholecystectomy
• Dilated intrahepatic biliary tree
CHOLEDOCHOLITHIASIS
 Diagnostic studies:
• Transabdominal US 13-55% sensitivity1, Endoscopic US higher
sensitivity and specificity for intraductal stones
• CT w/ contrast 65-88% sensitive2, CT cholangiography 93%
sensitive, 100% specific but difficult to perform3
• MRCP and ERCP both have sensitivities and specificities
approaching 100%4
 Treatment:
• ERCP with sphincterotomy, stone extraction, stent placement
• Successful in 90% of patients
• Complication rates 6-24%5, including pancreatitis
 DDx: cholangiocarcinoma, pancreatic adenocarcinoma
CHOLEDOCHOLITHIASIS
ERCP
MRCP
http://radiopaedia.org/images/2413474
http://www.jcdr.net/article_fulltext.asp?issn=0973709x&year=2013&volume=7&issue=9&page=1941&issn=0973709x&id=3365
CASE 4
50 y/o female admitted to the MICU for AMS. Vitals include temp
39, HR 110, BP 90/60, RR 20, sat 96% on RA. Exam reveals a
somnolent female with jaundice, scleral icterus, and guarding upon
palpation of the RUQ. Labs reveal: WBC 16,000, AST 160, ALT 200,
Alk Phos 650, T bili 8.0. Blood cultures are pending.
What is the most likely diagnosis?
CASE 4
50 y/o female admitted to the MICU for AMS. Vitals include temp
39, HR 110, BP 90/60, RR 20, sat 96% on RA. Exam reveals a
somnolent female with jaundice, scleral icterus, and guarding upon
palpation of the RUQ. Labs reveal: WBC 16,000, AST 160, ALT 200,
Alk Phos 650, T bili 8.0. Blood cultures are pending.
What is the most likely diagnosis?
Septic shock 2/2 Acute Cholangitis
CHOLANGITIS
 Infection of biliary tract 2/2 obstruction  biliary stasis & bacterial
overgrowth
• Ecoli & Klebsiella 70%, Enterococcus & Anaerobes (15%)
 Choledocholithiasis accounts for 60% of cases
 Other causes: pancreatic/biliary neoplasm, strictures, s/p ERCP,
choledochal cysts
 Clinical features:
• Charcot’s Triad: RUQ pain + Jaundice + Fever
•
Present in 60-79%
• Reynolds’ Pentad: Charcot’s triad + Septic shock + AMS
•
Present in ~15%
• Medical emergency if fever >40ºC, septic shock, peritoneal signs, or
bilirubin > 10
CHOLANGITIS
 Diagnosis/Treatment:
• IV abx (Zosyn, Unasyn, 3rd gen cephalasporin), IV fluids
• RUQ ultrasound as initial study
• When pt stable and afebrile for 48 hrs perform either:
• PTC (percutaneous transhepatic cholangiography) decompression via catheter
placement
• ERCP sphincterotomy
• T-tube insertion via laparotomy
• May need emergent procedures if pt doesn’t respond to IV abx (~15%)
SUMMARY
Cholelithiasis
Cholecystitis
Choledocholithiasis
Cholangitis
Stones in
gallbladder
Obstruction of
cystic duct 
Inflammation
Gallstones in
CBD
Infection of
biliary tract
Biliary colic
Murphy’s sign
Fever, ↑ WBC
Biliary colic,
jaundice
Charcot’s triad
CASE 5
You are asked to consult on a 62 y/o Caucasian female with pruritis for 4
months. She has also noticed progressive fatigue and a 5-lb wt loss. She
has intermittent nausea but no vomiting & denies changes in her bowel
habits. She denies any history of alcohol use, blood transfusions or illicit
drugs. She is widowed and had 2 heterosexual partners in her lifetime.
PMHx if significant only for hypothyroidism, for which she takes
levothyroxine. Her mother has Sjogren’s but there is no family hx of liver
disease.
On exam, she is mildly icteric, has spider angiomata on her torso, and the
following skin findings:
CASE 5: EXAM
What is this?
http://www.hxbenefit.com/wpcontent/uploads/2011/12/Xanthe
lasma.jpg
CASE 5: EXAM
Xanthelasma
http://www.hxbenefit.com/wpcontent/uploads/2011/12/Xanthe
lasma.jpg
CASE 5 CONT
Furthermore, you palpate a nodular liver edge 2cm below the right costal
margin. The remainder of the exam is unremarkable.
A RUQ ultrasound confirms your suspicion of cirrhosis. CBC and CMP
are pending.
What is the most appropriate next step?
A. 24-h urine copper
B. Antimitochondrial antibioties (AMA)
C. ERCP
D. Hepatitis B serologies
E. Serum ferritin
CASE 5
What is the most appropriate next step?
A. 24-h urine copper
B. Antimitochondrial antibioties (AMA)
C. ERCP
D. Hepatitis B serologies
E. Serum ferritin
The presence of cirrhosis in an elderly woman with no prior risk factors for
viral or alcoholic cirrhosis should raise the possibility of primary biliary
cirrhosis (PBC). AMA is + in 95% with low false positives. Liver biopsy
showing chronic inflammation and fibrous obliteration of intrahepatic
ducts can confirm the diagnosis.
PRIMARY BILIARY CIRRHOSIS




Autoimmune destruction of intrahepatic bile ducts
Associated with other autoimmune dz & often presents with fatigue and pruritus
Clinical jaundice when total bilirubin >2 mg/dL
Labs:
• Increased alk phos, bilirubin, and cholesterol (but no ↑ risk for CAD)
• + antimitochondrial Ab (AMA) in 95%
 Tx:
• Ursodeoxycholic acid (13-15 mg/kg/d)—reduces the overall toxicity of bile salt pool,
↑ survival
• Cholestyramine for puritis--↓ serum bile levels by binding & preventing gut absorption
• Fat soluble vitamins: Vit A, E, D, K
• Screen for osteoporosis (independent risk factor for Vit D deficiency)
• Liver transplant: ~20% recur
•
However without liver transplant, medial survival is 10-12 yrs after dx
CASE 6
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 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
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 7
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 7
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 8
44 y/o woman is evaluated for complaints of abdominal pain. She
describes the pain as postprandial burning pain. It is worse with spicy
or fatty foods and is relieved with antacids. She is diagnosed with a
gastric ulcer and treated appropriately for H. pylori. Following
treatment of H. pylori, her symptoms have resolved. During the
course of her evaluation for her abdominal pain, the patient has a
RUQ ultrasound that demonstrates the presence of numerous
gallstones, including in the neck of the gallbladder. The largest stone
measures 2.8cm. She is requesting your opinion regarding whether
treatment is required for her gallstone disease.
CASE 8
What is your advice to the patient regarding the risk of complications
and the need for definitive treatment?
A. Given the size and number of stones, prophylactic cholecystectomy is
recommended.
B. No treatment is necessary unless the patient develops symptoms of
biliary colic frequently and severely enough to interfere with the
patient’s life.
C. The only reason to proceed with cholecystectomy is the development of
gallstone pancreatitis or cholangitis.
D. The risk of developing acute cholecystitis is about 5-10% per year.
E. Ursodeoxycholic acid should be given at a dose of 10-15 mg/kg for a
minimum of 6 months to dissolve the stones.
CASE 8
What is your advice to the patient regarding the risk of complications and the need for definitive treatment?
A. Given the size and number of stones, prophylactic cholecystectomy is recommended.
B. No treatment is necessary unless the patient develops symptoms of biliary colic frequently and severely
enough to interfere with the patient’s life.
C. The only reason to proceed with cholecystectomy is the development of gallstone pancreatitis or cholangitis.
D. The risk of developing acute cholecystitis is about 5-10% per year.
E. Ursodeoxycholic acid should be given at a dose of 10-15 mg/kg for a minimum of 6 months to dissolve the
stones.
Only 1-2 % of patients with asymptomatic gallstone disease will develop compliations that will
require surgery yearly. 4 factors should be considered in evaluation for surgery:
1) Symptoms that are severe and frequent enough to necessitate surgery.
2) Hx of prior complications of gallstone disease (e..g pancreatitis, acute cholecystitis)
3) Presence of anatomic factors that increase the likelihood of complications (e.g. porcelain
gallbladder, congenital biliary tract abnormalities)
4) Large stones >3cm
Ursodeoxycholic acid can be used in some instances to dissolve gallstones. It acts to decrease
the cholesterol saturation of bile & allows the dispersion of cholesterol from stones. It is only
effective, however, for radiolucent stones <10mm.
CASE 9
62 y/o man has been in the ICU for the past 3 weeks following an automobile
accident results in multiple long-bone fractures and ARDS. He has been slowly
improving, but remains on mechanical ventilation. He is now febrile &
hypotensive, requiring vasopressors. He is being treated empirically with
cefepime and vancomycin. Multiple blood cultures are negative. He has no new
infiltrates on CXR. Labs show a risk in AST, ALT, bilirubin, and alk phos.
Amylase and lipase are normal. A RUQ ultraound shows sludge in the
gallbladder, but no stones. The bile duct is not dilated.
What is the next best step in the evaluation and treatment of this
patient?
A. Discontinue cefepime
B. Initiate clindamycin
C. Initiate metronidazole
D. Perform hepatobiliary scintigraphy (HIDA)
E. Refer for exploratory laparotomy
CASE 9
What is the next best step in the evaluation and treatment of this patient?
A. Discontinue cefepime
B. Initiate clindamycin
C. Initiate metronidazole
D. Perform hepatobiliary scintigraphy (HIDA)
E. Refer for exploratory laparotomy
Have a high index of suspicion for acalculous cholecystitis in critically ill patients who
develop decompensation during the course of treatment with no other apparent source of
infection. Some predisposing conditions include serious trauma or burns, postpartum after
prolonged labor, prolonged parenteral hyperalmentation, post op after orthopedic or major
surgery. US and CT scan typically only show biliary sludge, but may demonstrate
large/tense gallbladder. HIDA often showed delayed or absent gallbladder emptying. In
critically ill pts, a percutaneous cholecytostomy may be the safest immediate procedure to
decompress an infected gallbladder. Once the pt is stabilized, early elective cholecystectomy
should be considered. Metronidazole to cover anaerobes should be added, but would not
elucidate the underlying condition.
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!