HEPATOBILIARY BOARD REVIEWDarrell Laudate6-16-10 AM Report

First important to attempt to sort out hepatitis vs cholestatic liver disease

Approach to Abnormal LFTs

Hepatitis Hepatitis typically has elevations of

AST/ALT Present typically with fatigue, nausea, mild

upper abdominal pain, and juandice Recall the typical culprits of AST/ALT

elevations of the thousands Viral, toxins, shock/ischemia, occasionally AIH However, an acute increase in biliary pressue

(e.g. from choledocolithiasis can also cause transient AST elevations as high as 1000 but returns to normal after 48hrs

Serum Alk Phos may not be elevated

Cholestatic Diseases Typically heralded by elevations of Alk Phos Refers to injury of the microscopic ducts (e.g

PBC), large bile ducts, (e.g pancreatic cancer with CBD obstruction) or both (PSC)

Infiltrative diseases can also cause elevated Alk Phos yet near normal serum bilirubin

Any systemic inflammatory process such as an infection or immune disorder may result in a mixed pattern

Serum Bilirubin What is the fraction? Overproduction of bilirubin (e.g. hemolysis or

hematoma resorption) is associated with ≤ 20% conjugated bilirubin fraction

Hepatocyte dysfunction or impaired bile flow typically causes a hyperbilirubinemia with ≥ 50% conjugated bilirubin fraction Direct hyperbilirubinemia more common than indirect

in those with jaundice Abdominal pain, fever, and/or palpable GB with direct

hyperbilirubinemia suggests a large bile duct obstruction

Bilirubin (continued) Viral hepatitis risk factors, a total bilirubin >

15mg/dL and persistent AST/ALT elevations suggest hepatocellular injury

In patients with acute hepatocellular dysfunction, improvement in serum bilirubin levels often lags behind improvement in ALT/AST

Synthetic Liver Function (PT and Alb) Abnormal PT and Alb levels imply severe

hepatocellular injury Note that PT may also be elevated from Vit

K deficiency (via Abx administration, prolonged fasting, samll-bowel mucosal disorders (celiac), or severe cholestasis leading to fat-soluble deficiencies)

Vitamin K will improve the INR within 2 days with Vitamin K but will have no effect if due to liver disease with poor synthetic dysfunction

MKSAP Questions

Question 24 30-year-old woman is evaluated because of

an abnormal serum total bilirubin level detected when she had a life insurance examination. Medical history is unremarkable. Her only medication is an oral contraceptive agent. Physical examination is normal.

Labs: Hgb 13; MCV 90; Total bilirubin 2.4; Direct bilirubin 0.2; AST 23; ALT 25; Alk phos 90

Question 24 (continued) Which of the following is the most appropriate management at

this time? Discontinue the oral contraceptive agent

Cholestasis due to an oral contraceptive agent will typically cause conjugated (direct) hyperbilirubinemia and an elevated serum alkaline phosphatase level

Repeat the liver chemistry tests in 3 months

Evaluate for the presence of hemolysis Patients with hemolysis significant enough to cause unconjugated

hyperbilirubinemia typically low Hgb and abnormal MCV Schedule abdominal ultrasonography

Ultrasound may be a helpful study for direct hyperbilirubinemia as it is usually associated with liver disease

No additional diagnostic studies are indicated An isolated indirect (unconjugated) hyperbilirubinemia in an asymptomatic

patient with a normal Hgb level suggestive of Gilbert's syndrome, no further work-up indicated.

Gilbert’s Syndrome Common, benign inherited disorder

associated with indirect hyperbilirubinemia (with serum total bili > 3.0mg/dL but direct is 0.3mg/dL) Recall that the Bilirubin will typically rise during

illness or fasting periods Presumptive diagnosis can be made in an

otherwise healthy individual with an isolated indirect hyperbilirubinemia and a normal Hgb.

Question 32 37yo F with history of hypothyroidism (on

Levothyroxine) presents with 1-week history of fatigue, jaundice, and slight fever. She traveled to Mexico 5 months ago and received one dose of hepatitis A vaccine before her trip. Physical examination significant for mild jaundice and hepatomegaly.

Labs: CBC normal; TSH normal; AST 310; ALT 450; Alk phos 180; total bili 2.3

Question 32 (continued) Which will confirm the diagnosis?

Anti-mitochondrial antibody Serologic marker for PBC, a cholestatic disease, thus will have a typically higher Alk

Phos and T bili, lower AST/ALT Antinuclear antibody and anti–smooth muscle antibody

Most likely AIH given concomitant autoimmune thyroid disease and abnormal liver test results. Antinuclear antibody and anti–smooth muscle antibody titers should therefore be obtained (titers >1:80 for both assays support the diagnosis)

IgM antibody to hepatitis A virus (IgM anti-HAV) Does have travel risk factor but this was 5 months ago, incubation period for Hep A is

typically 2-6 weeks of exposure. Furthermor she also received 1 dose of the Hep A vaccine before travel, which typically protects people for at least 4 weeks

Serum acetaminophen Measurement of Acetaminophen level is appropriate for acute hepatitis of uncertain

cause but is typically associated with more significantly elevated AST/ALT values and is typically not associated with the week-long prodrome noted prior to presentation

Endoscopic retrograde cholangiopancreatography ERCP is indicated for evaluation of suspected biliary obstruction and could be

considered given the fever, jaundice and acutely elevated ALT/AST values but the absence of pain makes obstruction very unlikely

Autoimmune Hepatitis Typically develops in patients 20-40 years old Females> Males (3.6:1) 1/3rd to 1/2 have concomittant autoimmune disease Most pts have features of chronic disease but up to

40% will have an acute or fulminant presentation Fatigue present in 85%; jaundice (46%), anorexia

(30%), myalgias (30%), diarrhea (28%) Acne, hirsutism, menstrual irregularities, and fever are

less common Pruritis and weight loss are uncommon thus alternative

etiologies should be considered

AIH (continued) Some patients have features of both autoimmune hepatitis and a

cholestatic liver disease Referred to as an overlap syndrome

Exam often shows enlarged liver (78%) but otherwise typically normal despite presence of advanced disease

AST/ALT typically elevated (typically 150->1000 but often < 500) Serum gamma globulin ≥ 1.5 of upper limit of normal Mild hyperbilirubinemia (often < 3mg/dL) present in 83% Elevated AlkP often present but values > 2x normal suggest

another disorder ANA, Anti-smooth muscle Ab, or antibody to liver/kidney

microsome type 1 (anti-LKM1) is present in 87% typically titers ≥1:80 support diagnosis

Biopsy shows Interface hepatitis with portal plasma cell infiltrate.

Treatment of AIH Prednisone alone or Pred + Azathioprine associated

with remission in 80% at 3 years Relapse occurs in 50-86%, typically within 6 months of

withdrawal of therapy & associated with an increase in AST/ALT

Relapse treatment is same as initial treatment Liver transplant reserved for patients who do not

respond to treatment alone AIH can develop in the transplanted liver but is typically

mild Prognosis excellent for patients with treated AIH and is

same for that of healthy persons matched for age, sex, and geographic location

Question 133 21yo F brought to ER by her roommate for slurred

speech, tremor, and clumsy gait. Roommate last saw patient 2 days ago and does not know how long these changes have been present. Roommate believes the patient is health and does not take any prescription medications. However, a decline in her school performance over the last several months has been noted. PE shows she is jaundiced, tremulous, and delirious.

Labs: Hgb 8.2, WBC 6000/µL, plts 250,000/µLAST 250, ALT 275, AlkP 40, t bili 8.5 (direct 1.5)

Question 133 (continued) Which of the following studies is most likely to suggest the

diagnosis? Measurement of serum acetaminophen

Should always be obtained for evaluation of her AST/ALT but does not explain all of her features, e.g. prolonged cognitive decline, hemolytic anemia

Measurement of serum ceruplasmin Her chronic progressive decline along with her liver test abnormalities and

evidence of hemolytic anemia (via a disproportionate elevation of the T bili) are highly suggestive of Wilson’s. A ceruplasmin level <20mg/dL will be supportive of this diagnosis.

Measurement of ANA and serum gamma-globulin Helpful in diagnosis of AIH but this diagnosis would be hard to explain her

cognitive deficits and hemolysis Serologic studies for viral hepatitis

Should always be done with AST/ALT elevations but presentation and labs studies are lab studies are not strongly suggestive of viral hepatitis (more likely to have more significantly elevated AST/ALT; AlkP not likely

Urine Toxicology Screen Would explain her overt psychosis and hepatitis but again would not explain

her hemolytic anemia

Wilson’s Disease A condition of aberrant biliary copper excretion that

should be considered in a young patient with abnormal liver chemistry studies

A low ceruplasmin (esp. < 20mg/dL) is most likely to be strongly supportive of Wilsons

Hepatic Manifestations range from asymptomatic LFT elevations to fulminant hepatic failure

Copper deposition in the basal ganglia manifests as cognitive decline to overt pyschosis or delirium 1/3rd will present with Parkinsonian features

Also associated with cardiomyopathy, endocrine dysfunction, and Fanconi’s syndrome

Wilson’s Disease (continued) PE may show the Kayser-Fleischer rings

(usually can only be seen on slit lamp examination)

Labs may show variable AST/ALT elevations but Alk Phos will typically be lower than normal

A ceruplasmin will typically be < 20mg/dL with Wilson’s but this test is neither confirmatory nor diagnostic

Wilson’s Disease (continued) Wilson’s should be considered in a young

patient with characteristic clinical features and a serum ceruplasmin An elevated urine copper level (usually

>250ug/24h is also characteristic Biopsy will confirm the diagnosis via

hepatic copper concentration

Treatment of Wilson’s Pencillamine is in the initial therapy of choice, is

lifelong Side effects include neurologic deficits, hypersensitivity

reactions, bone marrow suppression, and autoimmune disorders

Trientine and zinc acetate are alternative agents Transplant indicated for those with fulminant disease

or ESLD who do not respond to medical therapy Significant improvement in neurologic function may

occur s/p transplantation thus severe neurologic dysfunction should not be a contraindication to transplantation

Question 9 42yo F w/ history of dysmenorrhea (on

estrogen/ progesterone) and hypothyroidism (on levothyroxine) has progressive fatigue without dyspnea, chest pain, or systemic symptoms. She sleeps well at night with no features of sleep apnea. Exam significant for slight but nontender thyromegaly and xanthomas on extensor surfaces.

Labs: nml CBC & TSH; AST 25, ALT 32, t bili 1.1, AlkP 278

Question 9 (continued) In addition to fasting serum lipid profile, which of the following

studies would most likely be helpful in establishing the diagnosis? Antimitochondrial antibody assay

80% of PBC pts report fatigue but presence of xanthomas and elevated AlkP are characteristeic of PBC; Antimitochondrial Antibody titer ≥ 1:40 present in > 90% of PBC pts

Serum 25-OH Vitamin D Although metabolic bone disease is associated with PBC, it vitamin D

deficiency would not explain exam/lab findings ERCP

Indicated for assessing cholestatic disease that affects large ducts (such as PSC) but would not be helpful in the diagnosis of PBC

Abdominal U/S Helpful in detecting bile duct dilatation for those with an elevated AlkP but

would be neither sensitive or specific for diagnosis PBC as U/S may be normal in PBC

PBC Chronic, progressive, autoimmune cholestatic liver disease Occurs predominantly in females (80-90%) between ages

of 40-60 years old 80% of PBC pts report fatigue but presence of xanthomas

and elevated AlkP are characteristeic of PBC Localized or generalized pruritis frequently develops; often in

the perineal area, or the palmar/plantar surfaces and worsens at night or in a warm environement

Jaundice or abdominal pain may also develop However many patients may be asymptomatic on presentation

Other autoimmune diseases are frequently present Metabolic Bone disease, hypercholesterolemia, and fat-

soluble Vitamin deficiencies are common

PBC (continued) Exam typically include:

Skin thickening and hyperpigmentation from repeated excorations

Exanthomas, xanthelasma and Hepatamegaly Advanced disease may have clinical

manifestations of portal hypertension

PBC (continued) Diagnostic triad associated with PBC includes

Cholestatic liver profile Positive Antimitochondrial antibody titers

>1:40 titers is serologic hallmark occurring in 90-95% of patients Compatible histologic findings on liver biopsy

AlkP and GGT are usually elevated 10x or more above normal

Bilirubin increases with disease progression thus is a helpful prognostic factor AMA titers do not correlate severity or prognosis

Biopsy characteristically shows nonsuppurative cholangitis plus findings ranging from bile duct lesions to cirrhosis

Question 105 42yo M is evaluated after an elevated

Alk Phos is noted during a life insurance exam. Denies pruritis, abdominal pain, or jaundice. He has loos bowel movements for many years and occasionally has rectal bleeding, which he attributes to hemorrhoids. PE is unremarkable.

Labs show a Hgb of 11.9, MCV 74, AST 45, ALT 52, Alk Phos 620, t bili 2.1 (1.6 direct)

Question 105 (continued) Which of the following diagnostic studies is most appropriate at this

time? Abdominal U/S

May show bile duct dilatation but this is a non-specific finding CT scan of the abdomen

May show bile duct dilatation but this is a non-specific finding ERCP

PSC most likely diagnosis but this is confirmed with ERCP or MRCP showing a string of beads” pattern of the biliary tree. His chronic loose stools and rectal bleeding is likely to due to ulcerative colitis that often accompanies PSC in most patients.

HIDA scan May be helpful for diagnosing acute cholecystitis, which is unlikely given lack of pain

CEA determination Metastatic colorectal cancer should be considered in a patient with rectal bleeding

and LFT elevations. However, the chronic nature of his altered bowel habits makes cancer unlikely. Furthermore, CEA is neither specific nor diagnostic for colorectal cancer

PSC Chronic cholestatic liver disease

characterized by progressive bile duct destruction and may lead to secondary biliary cirrhosis

3M : 1F, typically occurs between 20-30y 80% of PSC patients have IBD, typically

UC Conversely only 5% of UC develop PSC

Also associated with bacterial cholangitis, pigmented bile stones, steatorrhea, malabsoption and metabolic bone disease

PSC (continued) Most commonly presents as pruritis, jaundice,

abd pain, and fatigue Almost 50% are asymptomatic at initial diagnosis More advanced disease may have cirrhosis and its

associated complications Labs fit a cholestatic liver profile with Alk Phos

3-5x normal and mild hyperbilirubinemia ERCP or MRCP confirms diagnosis with findings

of multifocal strictures and dilatation of the intra- and extrahepatic bile ducts Aka “beads on a string

PSC (continued) Liver biopsy is usually done for staging

rather than dianosis and may show findings ranging from portal hepatitis to biliary cirrhosis Classic histologic lesion termed periductal

(“onionskin”) fibrosis is only in 10% of biopsy specimens

PSC (continued) PSC pts are at risk for developing

cholangiocarcinoma with a lifetime prevalence of 10-30% Detection at an early stage is difficult despite

availability of CA12-9, CEA, cytologic sampling and advanced imaging techniques

Also have risk for HCC if cirrhosis is present Pts with both PSC and UC have a higher risk of

colorectal neoplasia compared to UC alone pts Should have aggressive surveillance immediately

after diagnosis for both diseases

Treatment of PSC Management includes

Assessment of dominant strictures Treatment of superimposed bacterial

cholangitis Symptomatic therapy

Median survival after diagnosis is ~12 years Only transplant improves overall survival

and quality of life

Question 54 23yo F w/ no PMH presents with an 8-month

history of dyspnea and dry cough. Only medication is an OCP. PE significant for bilateral crackles on lung ausculation and mild hepatomegaly.

Labs: CBC normal; AST 45; ALT 55; Alk phos 430CXR shows shows mild diffuse pulmonary infiltrates but normal heart size. PPD is negative. Abdominal U/S shows mild hepatomegaly without bile duct dilatation.

Question 54 (continued) What is the most likely diagnosis?

Amyloid Causes HM and cholestasis but is usually accompanied by

evidence of other organ involvement suchas nephrotic syndrome or neuropathy. Also is rare in young pts.

Sarcoid High serum Alk Phos is commonly associated with infiltrative

liver disease and with presence of pulmonary infiltrates and hepatomegaly. Liver biopsy showing noncaseating granulomas will confirm the diagnosis of sarcoidosis

Tuberculosis Usually presents with a fever and + PPD

Primary biliary cirrhosis Disease of middle aged women and generally does not cause

pulmonary findings OCP induced cholestasis

Can rarely cause cholestasis but again would not be associated with pulmonary findings

Question 96 63yo F w/ 3 month history gradually increasing

abdominal distention and fatigue. She has no other symptoms and medical history is noncontributory. PE shows jaundice, mild muscle wasting, Xanthelasma spider angiomata, hepatosplenomegaly and moderate abdominal distension consistent with ascites.Labs shows Hgb 12.3, plts 102, AST 53, ALT 47, AlkP123, T bili 3.2, Alb 2.9, INR 1.3U/S shows hepatomegaly, coarse echotexture of liver, patent hepatic/portal vessels, mild splenomegaly, moderate ascites, and no bile duct dilatationParacentesis signficant for 80 PMNs, protein of 1.4g/dL, Albumin of 0.7g/dL

Question 96 (continued) Which of the following is the most likely diagnosis?

Key here is the SAAG (2.9-0.7 = 2.2) Peritoneal carcinomatosis

Has a low-gradient-high protein ascitic fluid Cirrhosis

SAAG > 1.1g/DL and fluid protein of < 2.5g/DL is consistent with siusoidal hypertension from chronic liver disease such as cirrhosis

Budd-Chiari syndrome High-gradient, high protein ascitic fluid

Dilated Cardiomyopathy High-gradient, high protein ascitic fluid

Serum-to-ascites albumin gradient (aka SAAG) Accurately identifies the presence of portal hypertension

Patients with heart failure and ascites can narrow their gradient during diuresis, whereas the SAAG in the setting of cirrhosis remains stable unless blood pressure or portal pressure decreases significantly.

Use of SAAG & Ascitic Fluid Protein to Determine cause of AscitesAscitic Protein

SAAG >1.1 SAAG < 1.1

< 2.5g/dL Cirrhosis Nephrotic Syndrome

> 2.5g/dL RHF, Budd Chiari

Malignancy, TB

Question 7 38yo F w/ HTN presents with a 3 month history of

intermittent, moderately severe epigastric pain that is sometimes associated with nausea and vomitting. The pain typically begins abruptly, lasts for 30-120 minutes before spontaneously abating, and sometimes awakens her at night. May be precipitated by eating. Current Meds include HCTZ. PE shows mild subjective epigastric tenderness only.

Labs show Hgb 12.1, QBC 10.1, AST 312, ALT 468, Alk Phos 190, T bili 0.7, Amylase 182Abd U/S shows several small gallstones but no GB wall thickening or pericholecystic fluid; negative U/S Murphy’s sign. CBD is 7mm (normal <6mm)

Question 7 (continued) Which of the following is the most likely cause of her abdominal

pain? Acute Pancreatitis

Unlikely given episodic (vs constant) nature of her pain. Additionally will typically see an Amylase rise of 2-3 times the upper limit of normal

Acute Cholecystitis U/S is not supportive of this diagnosis.

Choledocholithiasis

Typical presentation is with epigastric rather than RUQ pain that is intermittent, moderate-severe, not associated with N/V and can be nocturnal. LFTs particularly AST/ALT are almost always abnormal. CBD may be normal to slightly increased. Concomittant gallstones are present in 90%.

Peptic Ulcer Disease Typically present with epigatric pain that is relieved with eating

Chole this, Chole that,Holy Moley

Gallbladder Disease Overview

Cholelithiasis

Affects 20 million Americans but vast majority are asymptomatic

When symptoms do present, it is typically that of biliary pain or colic Once symptoms are present, ~50% will have

recurrent symptoms Therefore Cholecystectomy is indicated for most

symptomatic patients with laprascopic preferred over the open procedure

Patients with symptomatic gallstones have a 1-2% annual risk of developing complications Including acute cholecystitis, choledocholithiasis,

Mirizzi’s syndrome, and cholecystoenteric fistula

Acute Cholecystitis Most common complication of

cholelithiasis Due to impaction of a stone within the

cystic duct that subsequently becomes distended and GB may become inflamed

Secondary bacterial infection of bile/GB occurs in 50% of acute cholecystitis patients These patients will have fever and biliary

pain that persists for more than 6 hours Murphy’s sign is relatively specific on PE

Acute Cholecystitis (continued) Abd U/S may show the stone but also

frequently shows a thickened gallbladder wall and pericholecystic fluid

If findings are uncertain, a HIDA scan may fail to visualize the GB and confirms the suspicion of cystic duct obstruction

Acute Cholecystitis (continued) Treatment includes IVF and antibiotics

followed by lap chole Patients with repeated episodes of acute

cholecystitis characterized by a shrunken gallbladder containing stones or sludge Therefore paitents with more than one

episode of acute cholecystitis require cholecystectomy (lap vs open)

Choledocholithiasis ~5-19% of patients with cholelithiasis have

concomittant CBD stones These are stones that have migrated from the GB or

formed de novo within the CBD Also often asymptomatic but may cause

epigastric/RUQ pain (that radiates to the back), biliary pancreatitis, or life-threatening cholangitis

Should be suspected in a patient with cholelithiasis, development of abnormal LFTs (typically AST/ALT that can mimic that of hepatitis) and dilatation of the CBD on imaging Rarely the stone may be identified as well

Choledocholithiasis (continued) U/S while very sensitive in detecting

cholelithiasis is only 30-50% sensitive in detecting CBD stones but can be suggested by CBD dilatation

Helical CT scan is more sensitive (80%) EUS very senstive (90%)’ MRCP is less sensitive in detecting small CBD

stones ERCP is sensitive and allow for stone extraction

at the same time. It is therefore the preferred test when cholethiasis is suspected Also indicated for patients with acute cholangitis

and prior to lap cholecystectomy when choledocholithiasis is highly suspected on imaging and liver chemistry studies.

Management of Choledocholithiasis Dependent on comorbid conditions and

availability of experts (laproscopic, endoscopic, and intervential radiology) ERCP indication for those with cholangitis or for

those with pancreatitis complicated by cholangitis Contraindicated in patients with preveious enteric

reconstruction (e.g Billroth II, Roux-en-Y), complex stones > 1cm in diameter, or a biliary stricture

Laproscopic transcystic bile duct exploration also effective in detection and removal of CBD in 90% if expertise is available

Laproscopic choledochotomy with stone extraction +/- T-tube placement should be consider if transcystic bile duct exploration is unsuccessful

Choledocholithiasis & Pancreatitis Most common cause of pancreatitis worldwide Most patients with mild pancreatitis associated

with Choledocholithiasis will pass the stone spontaneously

These patients should usually undergo cholecystectomy prior to hospital discharge to prevent further episodes of pancreatitis. ERCP with sphincterotomy but without

cholecystectomy may be suitable for the elderly or high risk patients and can significantly reduce the risk of recurrent pancreatitis

Cholangitis Associated with biliary obstruction with

subsequent suppurative infection within the biliary tree Obstruction most often due to gallstones with ~6-

9% of patients with gallstone disease developing acute cholangitis

Charcot’s triad (pain, fever, and jaundice) occurs 50-100% of patients with cholangitis Hypotension and AMS occur in ~14%

All 5 are called Reynold’s pentad Mortality approaches 100% unless emergent

bile duct decompression is performed

Cholangitis (continued) Serum T bili is usually > 2mg/dL but may be

normal in early cholangitis Bacteremia occurs in 21-83%

Bile cultures grow bacteria in > 80% Aerobic and anaerobic GN bacilli and enterococci

are most commonly found CT scan or U/S can help differentiate

cholecystitis from cholangitis as well as detect a hepatic abscess or biliary obstruction

EUS may also be used to exclude bile duct stones if diagnosis of cholangitis is uncertain

Treatment of Cholangitis Immediate IV Abx with empiric coverage

for enteroccoci FQ preferred given their ability to enter an

obstructed biliary system ERCP +/- sphincterotomy or stent

placement is essential to remove the stone or bypass the obstruction

Question 3 51y F w/ history of well controlled DM2 presents

with acute onset of moderately severe, constant upper abdominal pain associated with nausea and vomiting. Current medications include an oral hypoglycemic agent, a statin, and low dose ASA. PE shows she is obese but afebrile and there is moderate upper abdominal pain without rebound

Labs show a T bili 0.8, AST 180, ALT 285, Alk Phos 152, Amylase 1010, Lipase 950

Question 3 (continued)Symptomatic treatment for pancreatitis is begun with IVF and pain management. 12 hours later, she has minimal symptoms.

Repeat Labs show a T bili 0.9, AST 82, ALT 100, Alk Phos 130, Amylase 580, Lipase 410

Question 3 (continued) Which of the following is the most appropriate next step in her

management? Abdominal U/S

Has classic presentation for acute gallstone pancreatitis with markedly elevated LFTs and pancreatic enzymes that rapidly return to normal. Abd U/S is required to exclude cholelithiasis as CT scan may not detect gallstones or sludge.

Cholescintigraphy (HIDA scan) May show cystic duct obstruction (indicative of chronic

cholecystistis but will not show gallstones ERCP

Indicated if LFTs become significantly abnormal, particularly if jaundice develops and U/S shows ductal dilatation

Laproscopic Cholecystectomy Although relapse rate for gallstone pancreatitis is high, lap chole

should be performed before hospital d/c but should not be performed until diagnostic studies are done

Question 17 78yo M w/ history of dementia, HTN, DM2 presents to the

ED by family members for concern of increasing somnolence and “not acting normal” for several hours. Current meds include HCTZ and pioglitazone. PE shows he is older than his stated age, temperature is 38.3C, pulse 100, BP 110/82. Mild jaundice is present; he is oriented to person and place but not year.

Labs shows Hgb 12.8, WBC 18.6, Cr 1.2, AST 186, ALT 230, Alk Phos 260, T bili 4.1, Alb 3.4Alb U/S shows normal liver architecture, CBD of 9mm (normal <6 mm), multiple gallstones, and no evidence of cholecystitis. A CXR shows emphysema.

Question 17 (continued) In addition to broad spectrum antibiotics, which of the following

is most appropriate at this time? CT scan of the abdomen

CT scan may identify alternative abnormalities with similary features and may be more sensitive than U/S for detecting CBD stones but the high likelihood of choledocholithiasis already present means that performing this test will delay what he really needs.

Biliary scintigraphy (HIDA scan) May confirm the presence of chornic cholecystitis or rarely show

ductal obstruction (via lack of contrast in duodenum) but will not show CBD stones

MRCP May identify the stones but has no therapeutic value

ERCP Severe cholangitis is evident by his fever, AMS, and juandice. LFTs

show bile duct obstruction and U/S shows gallstones and a minimally dilated CBD. Even with IV Abx, mortality is high unless ductal decompression is performed.

Question 44 68yo F presents with 2 day history of RUQ

pain, low-grade fever, and nausea. PE shows RUQ tenderness and possible fullness.

Labs show WBC 12.9, AST 35, ALT 50, Alk Phos 148, T bili 0.7, Alb 3.9Abd U/S shows a slightly dilated GB, markedly thickened GB wall w/ a small amount of pericholecystic fluid and multiple gallstones. Positive U/S Murphy’s sign is present but no CBD or pancreatic abnormalities are present.

Question 44 (continued) In addition to requesting a surgical consultation, which of the

following is most appropriate at this time? Pain meds and broad spectrum antibiotics

Acute cholecystitis is evident along with U/S findings that are highly specific for this diagnosis. Initial management should be IVF, IV ABx, and surgery c/s for elective cholecystectomy

Biliary scintigraphy (HIDA scan) Both sensitive and specific for diagnosis cholecystitis but would

not add any more information already obtained with U/S ERCP

Despite the mild LFT abnormalities, ERCP is not indicated given the lack of bile duct dilatation that would suggest choledocholithiasis

Percutaneous Cholecystostomy Appropriate for draining a markedly dilated GB in a patient who

cannot undergo cholecystectomy

Question 75 26yo M w/ AIDS has 2 month history of increasingly severe

epigastrium/RUQ abdominal pain that is variably precipitated by eating and is not associated with N/V. However, the pain is severe enough such that he cannot work. ROS significant for low-grade fever, loose stools, and weight loss of 4.5kg. Prior trial of HAART failed due to nonadherence; last CD4 count was 22. PE shows obvious signs of weight loss, thrush, a scaphoid but soft abdomen with mild RUQ pain but no HSM.

Labs show WBC of 3.1, repeat CD4 19, AST 62, ALT 90, Alk Phos 410, T bili 0.8, Alb 2.8Abd U/S shows slight intra- and extrahepatic bile duct dilatation with mural wall thickening; GB is slightly distended and has a thickened wall but no evidence of cholecystitis.

Question 75 (continued) In addition to counseling about the need for HAART, which of the

following is most appropriate at this time? Biliary scintigraphy (HIDA scan)

May confirm nonfunctioning GB but will not detect any findings already noted on U/S

CT scan of the abdomen Will confirm biliary tract obstruction and perhaps identify other

intra-abdominal abnormalities but his presentation and studies are suggestive of AIDS cholangiopathy for which CT scan has no therapeutic value

Colonoscopy Evaluation of loose stools is appropriate but routine non-invasive stool

studies should be done before colonoscopy is done ERCP

AIDS cholangiopathy is evident by his upper abdominal pain and obstructive liver injury pattern. ERCP will confirm the diagnosis but given the likely extrahepatic duct obstruction, ERCP with sphincterotomy may improve drainage and relieve pain caused by ampullary stenosis

AIDS cholangiopathy Most often affects paitents who have HIV infection with a

CD4 count < 200. Sclerosing cholangiopathy, papillary stenosis,

cholecystitis, extrahepatic biliary strictures and bile duct dilatation may occur together or independently in these patients

Associated with infections due to Cryptosporidium, Microsporidium, MAC, CMV

May present with cholangitis but will most commonly present with RUQ pain

Almost all have abnormal LFTs with a predominantly elevated Alk Phos

Most patients with AIDS cholangiopathy with papillary stenosis have symptomatic improvement after ERCP with sphincterotomy

Question 95 78yo F w/ history of CHF has 2 week history of

jaundice, loose stools, dark urine, and marked pruritis. Current medications are atorvastatin, HCTZ, and ACEI. PE discloses jaundice, mild temporal wasting, and fullness in the RUQ.

Labs show WBC of 8.6, plts 180, AST 99, ALT 140, Alk Phos 520, T bili 16.2, Alb 3.1U/S shows marked intrahepatic bile duct dilatation, dilated gall bladder, and normal distal CBD. CT scan confirms these findings and shows a normal pancreas.

Question 93 Which of the following should be done next?

EUS May identify a bile duct tumor, but this patient will require palliative

therapy, which this procedure cannot provide MRCP

May help localize the level of obstruction but this has already been done by U/S; MRCP cannot provide therapy either

Percutaneous transhepatic cholangiography Is an alternative to ERCP if ERCP is not technically possible or if local

expertise for PTC is lacking ERCP

New onset of obstructive jaundice in an elderly person is most often due to pancreatic or biliary tract carcinoma. U/S shows the obstruction in the CBD and pancreas is well-visualized and unremarkable (thus pancreatic carcinoma is unlikely). Since she is symptomatic, ERCP is preferable because it can confirm the diagnosis and provide therapy.

Cholangiocarcinoma Rare tumor (incidence of 1/100,000 in

US) Typically arises between the ages of 50-

70 years

60-80% arise near porta hepatis (aka Katskin’s tumor 20% are located in the distal bile duct 5% are intrahepatic

Cholangiocarcinoma (continued) ~90% will have obstructive jaundice

Advanced disease may also have HM or distended palpable GB (Courvoisier’s sign) if a distal obstruction is present

CA19-9 and CEA may be elevated but specificity is poor CEA cut-off of > 100U/ML increases the diagnostic

value CT scans or MRCP may suggest the diagnosis

and define the level of obstruction ERCP with brushings or biopsy may be

diagnotic EUS with biopsy may be helpful in diagnosising

a distal tumor

Treatment of Cholangiocarcinoma Hepatic resection may be effective for an intrahepatic

lesions 35% of patients with perihilar and ductal tumors can be

treated with resection and subsequent Roux-en-Y hepaticojejunostomy

Median survial for perihilar tumors is 12-24 months Radiation therapy provides some improvement in

survival rates when combined with other therapeutic modalities

Endoscopic or percutaneous biliary stent placement can be palliative

Photodynamic therapy may offer porlonged palliation and survival compared with stent alone

Pre- or postoperative chemotherapy does not improve survival or quality of life

Summary of High yield Hep topics

NAFLD EtOH disease Viral Hepatitis

Including the Hepatitis B window

Autoimmune Hepatitis PBC PSC Variceal Management Ascites and SAAG

evaluation Hepatic Encephalopathy

HRS HPS and other

exceptions to transplant HCC TIPS Pregnancy & Liver

disease Cholestasis of Liver

disease Genetic Liver Disease

Wilson’s, Hemochromatosis

References MKSAP Uptodate Sid Barrett’s Hepatology

Board Review 6/9/2010

And when in doubt for your boards, ask yourself: “What would Clint Eastwood do?”