LIVER FUNCTION TESTS:BILIARY

Megan Chan, PGY-1

UHCMC 2015

GUESS THE LFTS

CHOLELITHIASIS

If

Asymptomatic:

AST• Normal

ALT• Normal

Alk Phos• Normal

T bili• Normal http://radiopaedia.org/articles/cholelithiasis

If Pass a

Stone:

AST• Elevated

ALT• Elevated

Alk Phos• Elevated

T bili• Normal

ACUTE CHOLECYSTITIS

AST• Normal

ALT• Normal

Alk Phos• Elevated

T bili• Normal

http://radiopaedia.org/cases/acute-cholecystitis-4

http://radiopaedia.org/images/1780983

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 cases3 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/lumen/MedEd/Radio/curriculum/Procedures/HIDA_scan1.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 gallbladderPresentation: asymptomatic (~50%) biliary colic ascending cholangitis, obstructive jaundice, acute pancreatitisDefinitions 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

ERC

P

MRCP

http://radiopaedia.org/images/2413474

http://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2013&volume=7&issue=9&page=1941&issn=0973-709x&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 casesOther causes: pancreatic/biliary neoplasm, strictures, s/p ERCP, choledochal cystsClinical 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%)

Cholelithiasis

Cholecystitis Choledocho-lithiasis

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

SUMMARY

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/wp-content/uploads/2011/12/Xanthelasma.jpg

CASE 5: EXAM

Xanthelasmahttp://www.hxbenefit.com/wp-content/uploads/2011/12/Xanthelasma.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 copperB. Antimitochondrial antibioties (AMA)C. ERCPD. Hepatitis B serologiesE. Serum ferritin

CASE 5

What is the most appropriate next step?A. 24-h urine copperB. Antimitochondrial antibioties (AMA)C. ERCPD. Hepatitis B serologiesE. 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 ductsAssociated with other autoimmune dz & often presents with fatigue and pruritusClinical jaundice when total bilirubin >2 mg/dLLabs:

• 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. CeruloplasminC. Hepatitis B surface AgD. ERCPE. Toxicology screen

CASE 6

All of the following tests are indicated except?A. Antinuclear Ab (ANA)B. CeruloplasminC. Hepatitis B surface AgD. ERCPE. 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 observationB. ERCPC. Hepatic serologiesD. HIDA scanE. Serologies for antimitochondrial Ab

CASE 7

What is the most appropriate next management step?A. Antibiotics and observationB. ERCPC. Hepatic serologiesD. HIDA scanE. 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 8What 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 >3cmUrsodeoxycholic 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 cefepimeB. Initiate clindamycinC. Initiate metronidazoleD. 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 cefepimeB. Initiate clindamycinC. Initiate metronidazoleD. 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.pdfhttp://radiopaedia.orgSpecial thanks to Dr. Caroline Soyka for the inspiration!