Scenarios Ch.18 Liver & Gallbladder

Question 1

10. 42 y.o female. Right lower quadrant pain. No rebound tenderness. Imaging shows multilocular cycstic mass in region of right overy/distal right adnexa. Suggestion of a small mass lesion associated w/ left ovary as well. Biopsies are most consistent with tehmost common priary ovarian malgiancy. This is?
    a. Keratinizing squamous cell carcinoma
    b. Embryonal carcinoma
    c. Small cell carcinoma
    d. Serous cystadenocarcinoma
    e. Pheochromocytoma

Answer 1

Answer: serous cystadenocarcinoma
Tend to have more bilaterality
Other are more sporadic
Squamous cells not in ovary
Multilocular: compartmentalized
Most primary of gonads is different: germ cell mutations embryonal carcinoma
Small cell carcinoma don’t have good prognosis
Pheochromocytomas: endocrine cancer, catecolamines and metabolites produced

Question 2

6. A 58 year old obese man with right upper quadrant pain 3 weeks after an upper respiratory illness. He admits to drinking 3-5 oz of 40 proof spirits 2-3 days per weeks, as well as significant OTC medication usage for 2 weeks to treat his respiratory symptoms and chronic osteoarthritis. Elevated liver enzymes. Serology negative for hepatits markers. Ultrasound of liver shows normal size. Biopsy of liver shows focal steatosis and areas of centrilobular necrosis. Image B. Which of the following is most likely responsible for these latter biopsy findings?
   a. Alcohol
   b. Congestive heart failure
   c. Acetaminophen toxicity
   d. Von Gierke disease
   e. Arsenic poisioning

Answer 2

Answer: C. Acetaminophen toxicity
Association of acetaminophen and centrilobular necrosis**
Alcohol affects absorption of acetaminophen
Alcohol causes decrease in metabolism of acetaminophen → toxicity → necrosis
Image just correlative
Alcohol induce CYE…

Question 3

1 A previously healthy, 38-year-old woman has become
increasingly obtunded in the past 4 days. On physical examination,
she has scleral icterus, abdominal fluid wave, and
asterixis. She is afebrile, and her blood pressure is 110/55 mm
Hg. Laboratory findings show a prothrombin time of 38 seconds
(INR 3.1), serum ALT of 1854 U/L, AST of 1621 U/L,
albumin of 1.8 g/dL, and total protein of 4.8 g/dL. Serum or
blood levels of which of the following will most likely be
abnormal in this patient?
A Alkaline phosphatase
B Ammonia
C Amylase
D Anti-HCV
E Antinuclear antibody (ANA)

Answer 3

.
1 B The history points to an acute liver failure from fulminant
hepatitis with massive hepatic necrosis. The loss of hepatic
function from destruction of 80% to 90% of the liver results in
hyperammonemia from the defective hepatocyte urea cycle,
and this leads to hepatic encephalopathy within 2 weeks of the
onset of jaundice. An elevated alkaline phosphatase level suggests
extrahepatic or intrahepatic biliary obstruction. An elevated
amylase level suggests pancreatitis. Fulminant hepatitis
from HCV is rare. An autoimmune hepatitis with a positive
ANA finding is not likely to produce a fulminant hepatitis.

Question 4

2 A pathologic study of hepatic cirrhosis is performed.
There is collapse of reticulin with bridging fibrosis from deposition
of collagen in the space of Disse to form fibrous septae.
Which of the following cell types is activated under the influence
of cytokines to give rise to collagen-producing cells?
A Bile duct cell
B Endothelial cell
C Hepatocyte
D Macrophage
E Stellate cell

Answer 4

2 E Stellate cells (formerly Ito cells) may transform into
myofibroblasts secreting collagen when hepatocytes are
injured and elaborate free radicals and cytokines. This process
takes years, but is potentially reversible to some degree if the
injurious stimulus is removed. If sufficient functioning hepatic
parenchyma remains, the cirrhosis may be well-compensated.
The remaining cells listed do not produce collagen. The normal
space of Disse contains only a small amount of type IV
collagen. Trail tip: eating polar bear liver, which contains large
amounts of vitamin A, may produce vitamin A toxicity.

Question 5

3 A 54-year-old woman has a long history of chronic hepatitis
B infection and has had increasing malaise for the past
year. She was hospitalized 1 year ago because of upper gastrointestinal
hemorrhage. Physical examination now shows a
firm nodular liver. Laboratory findings show a serum albumin
level of 2.5 g/dL and prothrombin time of 28 seconds. Which
of the following additional physical examination findings is
most likely to be present in this woman?
A Caput medusae
B Diminished deep tendon reflexes
C Distended jugular veins
D Papilledema
E Splinter hemorrhage

Answer 5

3 A Cirrhosis with portal hypertension increases venous
collateral flow in esophageal submucosal veins, producing
varices, and in the abdominal wall, producing caput medusae.
Hyperreflexia, but not diminution of deep tendon reflexes,
can occur when hepatic encephalopathy develops from
decompensated cirrhosis. Right-sided heart failure, in which
the liver may be enlarged because of passive congestion, is
associated with distended jugular veins. Liver failure with
cirrhosis may lead to hepatic coma, but brain swelling with
papilledema is not a major feature. The coagulopathy from
decreased liver function may lead to purpuric hemorrhages,
but splinter hemorrhages of the nails are most characteristic
of embolization from infective endocarditis.
PBD9 823–824, 827–828 BP9 606–609 PBD8 857–860

Question 6

4 A 57-year-old woman has had increasing abdominal
enlargement for 6 months. During the past 2 days, she developed
a high fever. On physical examination, her temperature is
38.5° C. The abdomen is enlarged and diffusely tender, and
there is a fluid wave. Paracentesis yields 500 mL of cloudy
yellowish fluid. The cell count is 532/μL with 98% neutrophils
and 2% mononuclear cells. A blood culture is positive for
Escherichia coli. The representative gross appearance of her
liver is shown in the figure. Which of the following underlying
diseases most commonly accounts for these findings?
A α1-Antitrypsin deficiency
B Chronic alcohol abuse
C Hepatitis E viral infection
D Hereditary hemochromatosis
E Primary sclerosing cholangitis

Answer 6

4 B The diffuse nodularity with depressed scars between
the nodules is characteristic of cirrhosis, which led to her ascites
complicated by spontaneous bacterial peritonitis and septicemia.
The cirrhosis may be partially decompensated until
infection occurs. A common cause of cirrhosis in the Western
world is alcohol abuse. α1-Antitrypsin deficiency and hereditary
hemochromatosis can result in cirrhosis, but both of these
diseases are uncommon. In hereditary hemochromatosis, the
liver has a dark brown gross appearance caused by extensive
iron deposition. Of the various forms of viral hepatitis, those
caused by HBV or HCV are most likely to be followed by cirrhosis.
This complication is rare or nonexistent in HAV, HGV,
and HEV infections. In sclerosing cholangitis, there is portal
fibrosis, but not much nodular regeneration, so the liver is
green and hard and has a finely granular surface.

Question 7

5 A study of patients with ascites includes measurements
of serum and ascitic fluid protein levels. The serum-ascites
albumin gradient (SAAG) is calculated. Some patients are
found to have a high gradient, along with splenomegaly. They
are found to have serum albumin less than 2.5 g/dL Which
of the following conditions is most likely to produce a SAAG
greater than 1.1?
A Budd-Chiari syndrome
B Cirrhosis
C Nephrotic syndrome
D Pancreatitis
E Peritonitis

Answer 7

5 B The SAAG is calculated by subtracting the ascitic
albumin level from the serum albumin level, and it correlates
with portal pressure. With the architectural remodeling of
cirrhosis, there is portal hypertension and increased loss of
hepatic interstitial fluid with protein into the peritoneal cavity.
This is a transudative ascites. The serum albumin is likely
to be low with chronic liver disease because of decreased
synthetic capacity. The remaining choices include conditions
that lead to an exudative ascites with SAAG less than 1.1.

Question 8

6 A 65-year-old man with a history of alcohol abuse has
had hematemesis for the past day. Physical examination
reveals mild jaundice, spider angiomas, and gynecomastia.
He has mild pedal edema, normal jugular venous pulsation
(JVP), and a massively distended abdomen. Paracentesis
is performed and the fluid obtained shows accumulation of
protein-poor fluid that is free of inflammatory cells. Which of
the following factors is most likely to be responsible for the
collection of abdominal fluid in this man?
A Congestive heart failure
B Hepatopulmonary syndrome
C Hyperbilirubinemia
D Portosystemic shunts
E Splanchnic arterial vasodilation

Answer 8

6 E This patient most likely has alcoholic cirrhosis with
hepatic failure and portal hypertension. The ascites is
caused by portal hypertension which results from two major
changes: (1) mechanical obstruction to blood flow in the liver
due to scarring and compression of sinusoids by regenerating
nodules, and (2) splanchnic arterial vasodilation giving rise
to hyperdynamic circulation which leads to increased portal
venous blood flow. The latter is an important factor in the
pathogenesis of portal hypertension and consequent ascites.
The splanchnic arterial vasodilation is caused by increased
nitric oxide (NO) production in the splanchnic arterial bed.
This patient has no signs and symptoms of congestive heart
failure—notice the normal JVP. Hyperbilirubinemia in this
case is due to hepatic failure. In hepatopulmonary syndrome
there are pulmonary intravascular dilations due to NO synthesis
in the lung, not liver. Portosystemic shunts give rise to
esophageal varices that bleed to cause hematemesis.

Question 9

7 A 59-year-old man has had increasing dyspnea on exertion
for the past year. His dyspnea is worse in the upright
position and diminishes when he is recumbent. On physical
examination he has clubbing of the fingers. Exercise induces
a decrease in his Po2 that improves when he stops and lies
down. Which of the following liver abnormalities is he most
likely to have?
A Biliary obstruction
B Chronic inflammation
C Cirrhosis
D Metastases
E Steatosis

Answer 9

7 C Hepatopulmonary syndrome (portopulmonary
hypertension) is described. The cause is obscure, but the
result is pulmonary arterial vasoconstriction and ventilation-
perfusion (V˙ /Q˙ ) mismatches that lead to hypoxemia.
The remaining choices are conditions that do not cause portal
hypertension. Chronic inflammation and steatosis may
be seen with cirrhosis, but by themselves do not account for
portopulmonary hypertension. Metastases tend to be focal,
leaving residual functioning hepatic parenchyma. Biliary
obstruction leads to jaundice.

Question 10

8 A 50-year-old man has a history of chronic alcoholism,
but he stopped drinking alcohol 10 years ago. He has been taking
no medications. On physical examination, he is afebrile.
The abdomen is not enlarged, and there is no tenderness. The
liver span is normal. Serologic test results for hepatitis A, B,
and C are negative. The hematocrit is 35%. Which of the following
morphologic features is most likely to be present in his
liver?
A Concentric “onion-skin” bile duct fibrosis
B Hepatic venous thrombosis
C Interface hepatitis
D Massive hepatocellular necrosis
E Periportal PAS-positive globule deposition
F Portal fibrosis with regenerative nodules

Answer 10

8 F Portal bridging fibrosis and nodular hepatocyte regeneration
are features of cirrhosis. If liver stem cells support
hepatocyte regeneration, and ductular reactions are minimal,
then cirrhosis may be less progressive, and thin septae suggest
some degree of regression. The massive upper gastrointestinal
bleeding suggests esophageal varices as a consequence of portal
hypertension from cirrhosis. If the patient is currently not
drinking alcohol, no fatty change (steatosis) would be present.
The architectural changes of cirrhosis persist for decades
after cirrhosis develops. Concentric bile duct fibrosis is seen
in primary sclerosing cholangitis, which may be idiopathic or
may appear in association with inflammatory bowel disease.
Budd-Chiari syndrome in hepatic venous thrombosis leads
to hepatic enlargement, and it is rare. Interface hepatitis is a characteristic of chronic active HBV or HCV infection. Massive
hepatocellular necrosis may occur rarely as a complication of
HAV infection or ingestion of massive amounts of acetaminophen.
α1-Antitrypsin deficiency with the PAS-positive periportal
globules is associated with development of cirrhosis,
but this is far less common than alcoholic cirrhosis.

Question 11

9 A 58-year-old woman has experienced gradually
increasing malaise, icterus, and loss of appetite for the
past 6 months. On physical examination, she has generalized
jaundice and scleral icterus. She has mild right upper
quadrant tenderness; the liver span is normal. Laboratory
studies show total serum bilirubin of 7.8 mg/dL, AST of 190
U/L, ALT of 220 U/L, and alkaline phosphatase of 26 U/L.
A liver biopsy is done, and microscopic examination shows
the findings in the figure, along with portal bridging fibrosis.
These findings are most typical of which of the following
conditions?
A Choledocholithiasis
B Congestive heart failure
C HAV infection
D HCV infection
E Hemochromatosis
F Sclerosing cholangitis

Answer 11

9 D The figure shows interface hepatitis (formerly called
piecemeal necrosis but better termed apoptosis of hepatocytes) at the
limiting plate, with a mononuclear infiltrate, and Councilman
bodies. Liver disease that has persisted for 6 months, and histologic
evidence of hepatic necrosis with portal inflammation
and fibrosis, are features of chronic hepatitis. Of all the hepatitis
viruses, HCV is most likely to produce chronic hepatitis,
and HAV is the least likely to produce chronic disease. Choledocholithiasis
leads to extrahepatic biliary obstruction and an
elevated alkaline phosphatase level, but it is unlikely to produce
hepatocellular necrosis. Hepatic congestion with rightsided
heart failure produces centrilobular necrosis, but not
portal fibrosis. Hemochromatosis can produce portal fibrosis
and cirrhosis, but the liver cells show prominent accumulation
of golden brown hemosiderin pigment. Sclerosing cholangitis
leads to inflammation and obliterative fibrosis of bile ducts.

Question 12

10 A 27-year-old man develops malaise, fatigue, and loss
of appetite three weeks after a meal at the Trucker’s Cafe. He
notes passing dark urine. On physical examination, he has
mild scleral icterus and right upper quadrant tenderness.
Laboratory studies show serum AST of 62 U/L and ALT of
58 U/L. The total bilirubin concentration is 3.9 mg/dL, and
the direct bilirubin concentration is 2.8 mg/dL. His symptoms
abate over the next 3 weeks. On returning to the cafe, he finds
that the city’s health department has closed it. Which of the
following serologic test results is most likely to be positive in
this patient?
A Anti-HAV
B Anti-HBc
C Anti-HBs
D Anti-HCV
E Anti-HDV

Answer 12

10 A He most likely developed a mild, self-limited liver
disease from HAV infection after a meal at a restaurant with
consumption of contaminated food or water. The presence of
IgM anti-HAV indicates recent infection. The IgM antibody is
replaced within a few months by IgG antibodies, which impart
immunity to reinfection. The incubation period for HAV infection
is short, and the illness is short and mild, with no significant
tendency to develop chronic hepatitis. The most common
mode of infection for HAV is via the fecal-oral route. HBV and
HCV infections have longer incubation periods and are most
often acquired parenterally. HDV infection develops from coinfection
with HBV or by superinfection in a hepatitis B carrier.

Question 13

11 In a clinical study, patients with infectious hepatitis,
including viral hepatitis A, B, C, D, E, F, and G, are followed
for 5 years. During that time, prothrombin time, serum AST,
ALT, alkaline phosphatase, total bilirubin, and ammonia are
periodically measured. A liver biopsy is performed each year,
and the microscopic findings are recorded. Which of the following
is most likely the best predictor of whether a patient
with viral hepatitis will develop chronic liver disease that progresses
to cirrhosis?
A Degree to which hepatic transaminase enzymes are
elevated
B Length of time that hepatic enzymes remain
elevated
C Presence of chronic inflammatory cells in the portal
tract
D Presence of inflammatory cells in the hepatic
sinusoids
E Specific form of hepatitis virus responsible for the
infection

Answer 13

11 E The most important predictor of whether a patient
with viral hepatitis will develop chronic liver disease is the
etiologic agent that caused the hepatitis. Of all the hepatotropic
viruses, infection with HCV is the most likely to
progress to chronicity and ultimately to cirrhosis. HAV,
HEV, and HGV almost never cause chronic hepatitis. The
pattern of histologic change, the degree of transaminase
elevation, and the duration of transaminase elevation are
poor predictors of chronicity.

Question 14

12 A 30-year-old man had a 2-week episode of malaise,
fever, and jaundice 7 years ago. On physical examination,
there were needle tracks in the left antecubital fossa. Serologic
test results were positive for HBsAg, HBV DNA, and
IgG anti-HBc. Two years later, he was seen in the emergency
department because of hematemesis and ascites. Serologic
test results were similar to those reported earlier. Five years
after this episode, he now has a 5-kg weight loss, worsening
abdominal pain, and rapid enlargement of the abdomen over
the past month. Physical examination shows an increased liver
span. An increase in which of the following is most likely to be
diagnostic of this end stage of his disease?
A Serum alanine aminotransferase (ALT) level
B Serum alkaline phosphatase level
C Serum α-fetoprotein level
D Serum ammonia level
E Serum ferritin level
F Prothrombin time

Answer 14

12 C This intravenous drug user developed chronic HBV
infection, as evidenced by the persistence of HBsAg, HBV
DNA, and IgG anti-HBc antibodies. Of individuals with a
history of intravenous drug use, 80% to 90% are found to
have serologic evidence of HBV or HCV infection. Ruptured
varices and ascites suggest that this patient subsequently developed cirrhosis and portal hypertension. His final presentation
of weight loss and rapid enlargement of the abdomen
suggests that a hepatocellular carcinoma has developed,
and in most cases is confirmed by an elevated α-fetoprotein
level. The other test findings, including prolonged prothrombin
time, increased ALT level, and increased ferritin
level, all indicate chronic liver disease. Any mass lesion in
the liver is associated with an elevated alkaline phosphatase
level. An increasing blood ammonia level indicates marked
liver failure.

Question 15

13 A 42-year-old man experiences malaise and increasing
icterus for 2 weeks. Physical examination shows jaundice, but
there are no other significant findings. Serologic test results are
positive for IgM anti-HAV and negative for anti-HCV, HBsAg,
and IgM anti-HBc. Which of the following outcomes is most
likely to occur in this man?
A Chronic active hepatitis
B Complete recovery
C Fulminant hepatitis
D Hepatocellular carcinoma
E Negative serologic test results

Answer 15

13 B The detection of IgM anti-HAV indicates acute infection.
Progression of HAV infection to chronic hepatitis does
not occur, but a few cases are complicated by fulminant hepatitis.
HAV viremia is transient, so blood-borne transmission
of HAV is rare. HAV is spread by the fecal-oral route, such
as raw shellfish from a bay in which raw sewage is dumped

Question 16

14 An epidemiologic study is conducted in Singapore of
patients infected with HBV. These patients are followed for
10 years from the time of diagnosis. Historical data are collected
to determine the mode of transmission of HBV. The
patients receive periodic serologic testing for HBsAg, anti-
HBs, and anti-HBc, and serum determinations of total bilirubin,
AST, ALT, alkaline phosphatase, and prothrombin time.
The study identifies a small cohort of patients who are found
to be chronic carriers of HBV. Which of the following modes of
transmission of HBV are most likely to be associated with the
development of carrier state?
A Blood transfusion
B Heterosexual intercourse
C Needlestick injury
D Oral ingestion
E Vertical transmission

Answer 16

14 E In regions where HBV is endemic, vertical transmission
produces a carrier rate of 90% to 95%. However,
successful implementation of a national childhood HBV
immunization program can lead to a low prevalence of
HBsAg among children and adolescents. Singapore achieved
the World Health Organization goal to reduce the prevalence
of chronic HBV infection. Development of viral hepatitis
requires an immune response against virus-infected cells. In
immunocompetent individuals, HBV induces T cells specific
for HBsAg that cause apoptosis of infected liver cells. During
the neonatal period, immune responses are not fully developed;
hepatitis does not occur. The high carrier rate is medically
significant because it increases the risk of hepatocellular
carcinomas 200-fold. In populations with a high carrier rate,
coexistent cirrhosis may be absent in 50% of patients. In contrast,
in places where HBV is not endemic, cirrhosis is present
in 80% to 90% of patients who develop liver cancer. HBV
infection from blood transfusion is rare because of screening
of blood products. Transmission of HBV via sexual contact is
uncommon and induces a carrier state in a few cases; in most
cases, an immune response is elicited. Oral transmission of
HAV is common (but not HBV or HCV). The risk of acquiring
HBV through needlestick injury is 1% to 6%.

Question 17

15 A 40-year-old woman wishes to donate blood to help
alleviate the chronic shortage of blood for transfusion. She is
found to be positive for HBsAg and is excluded as a blood
donor. She feels fine. There are no significant physical examination
findings. Laboratory findings for total serum bilirubin,
AST, ALT, alkaline phosphatase, and albumin are normal.
Further serologic test results are negative for IgM anti-HAV,
anti-HBc, and anti-HCV. Repeat testing 6 months later yields
the same results. Which of the following is the most appropriate
statement regarding the pathophysiology of this patient’s
condition?
A Chronic carrier state with no therapy indicated
B Clinically overt hepatitis will occur within 1 year
C Erroneous test results that need to be repeated
D Hepatitis B vaccination series is now required
E Infection acquired through intravenous drug use

Answer 17

15 A Persistence of HBsAg in serum for 6 months or
more after initial detection denotes a carrier state. Worldwide,
most individuals with a chronic carrier state for HBV
acquired this infection in utero or at birth. Only 1% to 10% of
adult HBV infections yield a chronic carrier state. The carrier
state is stable in most individuals, the so-called “inactive”
carrier state, without elevation in liver enzymes, and some
infected persons may eventually clear the virus. There is currently
no therapy to aid this viral clearance Vaccination is
useful to prevent infection, not clear the virus, although carriers
become a reservoir for infection of others.

Question 18

16 A 41-year-old woman who works as a tattoo artist has
had increasing malaise and nausea for the past 2 weeks. On
physical examination, she has icterus and mild right upper
quadrant tenderness. Laboratory studies show serum AST of
79 U/L, ALT of 85 U/L, total bilirubin of 3.3 mg/dL, and direct
bilirubin of 2.5 mg/dL. She continues to have malaise for the
next year. A liver biopsy is done, and microscopic examination
shows minimal hepatocyte necrosis, mild steatosis, and
minimal portal bridging fibrosis. An infection with which of
the following viruses is most likely to produce these findings?
A HAV
B HBV
C HCV
D HDV
E HEV

Answer 18

16 C Necrosis with portal bridging suggests chronic hepatitis.
Mild steatosis is seen in HCV infection. The incidence of
chronic hepatitis is highest with HCV infection. More than
50% of individuals infected with this virus develop chronic
hepatitis, and many cases progress to cirrhosis. This is partly
because the IgG antibodies against HCV that develop after
acute infection are not protective.

Question 19

17 A study is conducted of patients who are infected with
hepatitis virus A, B, C, D, E, or G. The patients are categorized
according to the type of virus and are followed over the next
10 years. They receive periodic serologic testing to determine
whether they are producing antibodies to the virus with which
they were infected. Analysis of the data shows that a cohort
of these patients developed antibodies, but subsequently did
not clear the virus until treated with pegylated interferon and
ribavirin. Which of the following forms of viral hepatitis was
most likely to infect this subset of patients?
A HAV
B HBV
C HCV
D HDV
E HEV
F HGV

Answer 19

17 C Antibodies to hepatitis C do not confer protection
against reinfection. HCV RNA remains in the circulation,
despite the presence of neutralizing antibodies. Treatment
strategies may also target viral polymerase and protease,
similar to antiretroviral regimens for HIV infection. In infections
with HAV, HBV, HDV, HEV, or HGV, development
of IgG antibodies offers lifelong immunity. An HBV vaccine
exists for this purpose.

Question 20

18 A 52-year-old woman has experienced worsening malaise
during the past year. On physical examination, she has
mild scleral icterus. There is no ascites or splenomegaly. Serologic
test results are positive for IgG anti-HCV and HCV RNA
and negative for anti-HAV, HBsAg, ANA, and antimitochondrial
antibody. The serum AST level is 88 U/L, and ALT is 94
U/L. Her condition remains stable for months. Which of the
following morphologic findings is most likely to be present in
this patient’s liver?
A Concentric “onion-skin” bile duct fibrosis
B Copper deposition within hepatocytes
C Granulomatous bile duct destruction
D Hepatic venous thrombosis
E Interface hepatitis
F Massive hepatocellular necrosis
G Microvesicular steatosis

Answer 20

18 E This patient has evidence of HCV infection with
symptoms of liver disease for 1 year. Clinically, she has
chronic hepatitis (>6 months), which may have followed
an asymptomatic acute HCV infection. The anti-HCV IgG
antibody is not protective. This is supported by continued
HCV viremia. Approximately 85% of cases of HCV
progress to chronic hepatitis, but fulminant hepatitis is
uncommon. Chronic hepatitis is characterized by apoptosis
of hepatocytes at the interface between portal tracts
and the liver lobule. This eventually leads to cirrhosis with
portal bridging fibrosis and nodular regeneration. At this
time, however, the patient has no signs or symptoms of
cirrhosis. Concentric bile duct fibrosis occurs in sclerosing
cholangitis, which may be idiopathic or, more commonly,
is associated with inflammatory bowel disease. Copper
deposition is characteristic of Wilson disease, which may
be associated with chronic hepatitis and cirrhosis, but it
is not related to the much more common HCV infection.
Granulomatous bile duct destruction suggests primary
biliary cirrhosis. Budd-Chiari syndrome in hepatic venous
thrombosis leads to hepatic enlargement and necrosis and
to ascites.

Question 21

19 A 27-year-old man with a history of intravenous drug
use is known to have been infected with hepatitis B virus
for the past 6 years and has not been ill. He is seen in the
emergency department because he has had nausea, vomiting,
and passage of dark-colored urine for the past week.
Physical examination shows scleral icterus and mild jaundice.
Neurologic examination shows a confused, somnolent
man oriented only to person. He exhibits asterixis. Laboratory
studies show total protein, 5 g/dL; albumin, 2.7 g/dL; AST,
2342 U/L; ALT, 2150 U/L; alkaline phosphatase, 233 U/L;
total bilirubin, 8.3 mg/dL; and direct bilirubin, 4.5 mg/dL.
Superinfection with which of the following viruses has most
likely occurred in this man?
A HAV
B HCV
C HDV
D HEV
E HGV

Answer 21

19 C HDV cannot replicate in the absence of HBV; isolated
HDV infection does not occur. The evidence for
chronic hepatitis B is the presence of HBsAg and anti-HBc
IgG antibody in the absence of anti-HBc IgM antibody.
Confirmatory serologic evidence of recent HDV infection is
the presence of anti-HDV IgM antibodies. HBV and HDV
infections are likely to occur in drug users who inject parenterally.
When HDV infection is superimposed on chronic
HBV, three outcomes are possible: mild hepatitis B may be
converted to fulminant disease; acute hepatitis may occur
in an asymptomatic HBV carrier; or chronic progressive
disease may develop, culminating in cirrhosis. The other
listed viruses can cause infection by themselves.

Question 22

20 A 36-year-old, G3, P2, woman living in New Delhi, India,
has worsening nausea and malaise for a week. On physical
examination her sclerae are icteric. Her liver span is increased
and the liver edge is tender. She is at 16 weeks’ gestation.
Laboratory studies show her serum AST is 495 U/L and ALT
is 538 U/L. She recovers and hepatic function returns to
normal, but spontaneous abortion occurs at 18 weeks. Epidemiologic
studies show a point source of contaminated water
for infection. With which of the following viruses was she
most likely infected?
A Cytomegalovirus (CMV)
B Epstein-Barr virus (EBV)
C Hepatitis E virus (HEV)
D Herpes simplex virus (HSV)
E Yellow fever virus

Answer 22

20 C HEV infections are most common in East and South
Asia. Spread is by a fecal-oral route. Most persons have a
subclinical infection, but 1 in 7 develops acute hepatitis;
death is uncommon, except in pregnant women. HEV does
not go on to chronic hepatitis. CMV and HSV can be congenital
infections, but are unlikely to affect the maternal liver
significantly; CMV is a significant cause for liver failure in
orthotopic transplants, and both can affect immunocompromised
persons. EBV can affect the liver as part of infectious
mononucleosis, but the infection is typically mild. Yellow
fever is seen in tropical and subtropical regions of Africa and
South America and is spread via mosquitoes

Question 23

21 A 29-year-old man has developed malaise and nausea
2 months following intercourse with a new sexual contact. He
notes scleral icterus 10 days later. He now has two more sexual
contacts who subsequently become ill. Serologic testing shows
that he is HbsAg positive, HAV-IgM negative, and anti-HCV
negative. His AST is 77 IU/L and ALT 95 IU/L. A month later
his anti-HBs is positive. Which of the following is the most
likely course of his illness?
A Asymptomatic illness
B Chronic hepatitis
C Fulminant hepatic failure
D Hepatitis with recovery
E Macronodular cirrhosis

Answer 23

21 D He has hepatitis B virus (HBV) infection. The most
common outcome with HBV infection is recovery. He was
symptomatic, as evidenced by icterus, malaise, and nausea.
His ALT and AST were not very high. Presence of anti-
HBs is consistent with recovery. However, though recovery
occurs, in the acute phase of the illness beyond incubation,
he is highly infective to others. Fulminant hepatitis is infrequent
with HBV, <1% of cases. Only 10% of cases progress to
chronic hepatitis, and a subset of those go on to cirrhosis.

Question 24

22 A 53-year-old woman from southern China has had
fever, right upper quadrant pain, and jaundice for the past
6 months. On examination she has an increased liver span. An
abdominal CT scan shows a 5-cm right hepatic tumor with a
branching, infiltrative appearance. A liver biopsy is performed
and on microscopic examination shows irregular invasive
glands in a desmoplastic stroma. This patient is most likely to
have chronic infection with which of the following?
A Clonorchis sinensis
B Echinococcus granulosus
C Plasmodium vivax
D Mycobacterium tuberculosis
E Salmonella typhi

Answer 24

22 A Parasitic liver flukes are endemic to East Asia and
Southeast Asia. Infection may be asymptomatic for years, but
can progress to a chronic phase complicated by recurrent pyogenic
cholangitis and jaundice. There is risk for development
of cholangiocarcinoma, the second most common primary
hepatic malignancy. The other listed foils do not carry a risk for
neoplasia. Echinococcosus leads to hydatid disease, but not to
malignancy. The extraerythrocytic phase of malaria with plasmodium
infection includes the liver. Disseminated tuberculosis
produces granulomas, usually small and multifocal. Typhoid
fever can be a systemic disease with liver involvement.

Question 25

23 A 31-year-old woman has experienced increasing malaise
for the past 4 months. Physical examination yields no remarkable
findings. Laboratory studies show total serum protein of
6.4 g/dL, albumin of 3.6 g/dL, total bilirubin of 1.4 mg/dL,
AST of 67 U/L, ALT of 91 U/L, and alkaline phosphatase of 99
U/L. Results of serologic testing for HAV, HBV, and HCV are
negative. Test results for ANA, anti-liver kidney microsome-1,
and anti–smooth muscle antibody are positive. A liver biopsy
is done; microscopically, there are minimal portal mononuclear
cell infiltrates with minimal interface hepatitis and mild portal
fibrosis. What is the most likely diagnosis?
A α1-Antitrypsin deficiency
B Autoimmune hepatitis
C Chronic alcoholism
D HDV infection
E Isoniazid ingestion
F Primary biliary cirrhosis

Answer 25

23 B Autoimmune hepatitis is a chronic liver disease of
unknown cause in which antibodies to hepatocyte structural
components cause progressive necrosis of hepatocytes, leading
to cirrhosis and liver failure. Patients tend to improve
with glucocorticoid therapy. α1-Antitrypsin deficiency and
Wilson disease can lead to chronic hepatitis and cirrhosis,
but autoimmune markers are absent. Chronic alcoholism is
not associated with formation of autoantibodies. Because this
patient does not have evidence of HBV infection, there can be
no superinfection with HDV. Isoniazid may cause an acute
or chronic hepatitis, but without autoantibodies. Patients
with primary biliary cirrhosis often have antimitochondrial
antibody (which also can be seen in autoimmune hepatitis),
but the bilirubin concentration and alkaline phosphatase
level would be much higher in primary biliary cirrhosis

Question 26

24 A study of hepatic injury is undertaken. Patients with
fulminant hepatic failure are found to have microscopic
evidence in biopsies for ballooning hepatocyte degeneration,
canalicular bile plugs, bridging necrosis, and minimal inflammation.
Which of the following is most likely to cause this
pattern of hepatic damage?
A α1-Antitrypsin deficiency
B Chronic alcohol abuse
C Hepatitis C virus infection
D Isoniazid toxicity
E Wilson disease

Answer 26

24 D Acute hepatic injury is described. Isoniazid used to
treat tuberculosis may produce hepatotoxicity, and in most cases it is mild, but in some cases it leads to massive hepatic
necrosis. There may be minimal symptoms until severe
injury has occurred. The remaining choices include conditions
that are more likely to produce a pattern of chronic
hepatic injury.

Question 27

25 A 66-year-old woman with a history of chronic alcohol
abuse has had headaches and nausea for the past 4 days. She
has become increasingly obtunded. On physical examination
she has right upper quadrant tenderness, tachycardia, tachypnea,
and hypotension. Laboratory studies show serum AST of
475 U/L, ALT of 509 U/L, alkaline phosphatase of 23 U/L, total
bilirubin of 0.9 mg/dL, albumin of 3.8 g/dL, and total protein
of 6.1 g/dL. She is treated with N-acetylcysteine. Which of the
following drugs has she most likely ingested in excess?
A Acetaminophen
B Aspirin
C Ibuprofen
D Meperidine
E Oxycodone

Answer 27

25 A In the setting of chronic liver disease, ingestion of
acetaminophen is more likely to produce hepatotoxicity
because detoxification by conjugation is exceeded. This leads
to metabolism by cytochrome P-450 to the toxic metabolite
N-acetyl-p-benzoquinineimine (NAPQI), which accumulates
beyond the capacity of glutathione. The N-acetylcysteine
increases available glutathione. Aspirin ingestion is a cause
for Reye syndrome in children. Ibuprofen, which is a nonsteroidal
anti-inflammatory drug (NSAID), meperidine, and
oxycodone do not have significant hepatotoxicity.

Question 28

26 A 63-year-old man with a 30-year history of alcohol
abuse notes hematemesis for the past day. On examination, he
has ascites, mild jaundice, and an enlarged spleen. He also has
gynecomastia, spider telangiectasias of the skin, and testicular
atrophy. Rectal examination indicates prominent hemorrhoids
and a normal-sized prostate. Emergent upper endoscopy
shows dilated, bleeding submucosal vessels in the esophagus.
Laboratory studies show total protein, 5.9 g/dL; albumin,
3.2 g/dL; AST, 137 U/L; ALT, 108 U/L; total bilirubin, 5.4 mg/d;
prothrombin time, 20 seconds; ammonia, 76 μmol/L; and
hematocrit, 21%. Which of the following pathologic findings in
his liver is most likely to explain the hematemesis?
A Cholangitis
B Cholestasis
C Cirrhosis
D Hepatitis
E Steatosis

Answer 28

26 C Portal fibrosis and nodular hepatocyte regeneration
are typical features of chronic alcohol abuse. Spider
telangiectasias (angiomas) refer to vascular lesions in the
skin characterized by a central, pulsating, dilated arteriole
from which small vessels radiate. These lesions result from
hyperestrogenism (which also contributes to the testicular
atrophy). The failing liver is unable to metabolize estrogens
normally. Spider angiomas are a manifestation of hepatic
failure. Ascites, splenomegaly, hemorrhoids, and esophageal
varices all are related to portal hypertension from cirrhosis
and the resultant collateral venous congestion and
dilation. The other listed findings do not explain portal
hypertension.

Question 29

27 A 52-year-old man has had increasing malaise and
swelling of the lower legs for the past 4 months. On physical
examination, he is afebrile and normotensive. There is pitting
edema to the knees. The abdomen is slightly distended
with a fluid wave, but there is no tenderness. The liver span
is increased. Laboratory studies show total serum protein
of 5 g/dL, albumin of 2.2 g/dL, AST of 65 U/L, ALT of
65 U/L, alkaline phosphatase of 93 U/L, and total bilirubin of
1.8 mg/dL. A liver biopsy is performed and the microscopic
appearance with trichrome stain is shown in the figure. Ingestion
of which of the following is most likely to have caused
this illness?
A Acetaminophen
B Allopurinol
C Aspirin
D Chlorpromazine
E Ethanol
F Isoniazid

Answer 29

27 E The figure shows macrovesicular steatosis (fatty
change) of the liver with early fibrosis. The most common
cause of fatty liver and fibrosis is chronic alcoholism. In
patients with no history of significant ethanol ingestion, a
nonalcoholic steatohepatitis may be considered, with obesity,
diabetes mellitus, or both as possible causes. Excessive
acetaminophen ingestion can cause centrilobular necrosis or
diffuse necrosis. Allopurinol toxicity can cause granuloma
formation. Aspirin may be associated with a microvesicular
steatosis as Reye syndrome in children. Chlorpromazine can
lead to cholestasis. Isoniazid use can be complicated by acute
injury and granuloma formation.

Question 30

28 A 48-year-old man has noticed increasing abdominal
girth and a yellowish color to his skin over the past 5 months.
On physical examination, he has scleral icterus and generalized
jaundice. His abdomen is distended, and a fluid wave is
present. Laboratory studies include total serum bilirubin of
5.2 mg/dL, direct bilirubin of 4.2 mg/dL, AST of 380 U/L,
ALT of 158 U/L, alkaline phosphatase of 95 U/L, total proteinof 6.4 g/dL, and albumin of 2.2 /dL. The prothrombin time is
18 seconds, and the partial thromboplastin time is 30 seconds.
The blood ammonia level is 105 mmol/L. What is the most
likely cause of these findings?
A Acute HAV infection
B Alcoholic liver disease
C Choledocholithiasis
D Metastatic adenocarcinoma
E Primary biliary cirrhosis

Answer 30

28 B The elevated transaminase levels, some loss of liver
function with abnormal prothrombin time, and cholestasis
are not specific for a given type of liver injury. An AST level
that is higher than the ALT level is characteristic, however,
of liver cell injury associated with chronic alcoholism. In this
patient, the disease is decompensating, as evidenced by the
elevated blood ammonia level. HAV is typically a mild disease
without a preponderance of direct bilirubin. Choledocholithiasis
results in a conjugated hyperbilirubinemia, but without the high ammonia level that is evidence of liver failure.
Metastases are unlikely to obstruct all biliary tract drainage
or lead to liver failure severe enough to cause elevations
of blood ammonia. Primary biliary cirrhosis is rare, particularly
in men, and the alkaline phosphatase level would be
much higher.

Question 31

29 A 38-year-old man feels acutely ill with nausea, upper
abdominal pain, and jaundice following a heavy bout of
drinking over the weekend. On physical examination, there is
right upper quadrant tenderness. Laboratory studies include
a total WBC count of 16,120/mm3 with 82% segmented neutrophils,
8% bands, 8% lymphocytes, and 2% monocytes. The
total serum bilirubin is 4.9 mg/dL, AST is 542 U/L, ALT is
393 U/L, and alkaline phosphatase is 118 U/L. A liver biopsy
is obtained and the microscopic appearance is shown in the
figure. What is the nature of the accumulations seen in the
biopsy?
A α1-Antitrypsin globules
B Lysed red cells
C Bile pigment
D Hemosiderin deposition
E Mallory-Denk bodies
F Viral inclusions (HBsAg)

Answer 31

29 E This is acute alcoholic hepatitis. The figure shows
globular eosinophilic cytoplasmic inclusions called Mallory-
Denk bodies. These cytokeratin inclusions are characteristic of,
but not specific for, alcoholic hepatitis. There also are areas of
hepatocyte necrosis surrounded by neutrophils. Some neutrophils
can be seen in the figure. Centrilobular congestion
can lead to centrilobular necrosis without inflammation or
Mallory-Denk bodies. Cholestasis is marked by plugs of yellow-
green bile in canaliculi. Hemosiderin appears granular
and brown on H&E staining, but it is blue with Prussian blue
stain. Periportal PAS-positive globules are characteristic of
α1-antitrypsin deficiency; the globules tend to be smaller than
Mallory-Denk bodies, and there is no acute inflammation.

Question 32

30 A longitudinal study is conducted of non-alcoholics with
type 2 diabetes mellitus, dyslipidemia, and BMI >30. There is
an increasing prevalence of liver disease in these persons over
time. Which of the following microscopic pathologic findings
is most characteristic for the livers of these persons?
A Apoptosis
B Cholestasis
C Cirrhosis
D Hemosiderosis
E Inflammation
F Steatosis

Answer 32

30 F Nonalcoholic fatty liver disease (NAFLD) occurs in
persons with metabolic syndrome/type 2 diabetes mellitus,
with impaired fatty acid and lipoprotein metabolism. Some
cases may go on to steatohepatitis with fibrosis and even cirrhosis
(so-called cryptogenic cirrhosis when alcohol use could
not be blamed, but remember to ask the CAGE questions).
Though there may be hepatocyte loss and inflammation, these
are not the most prominent features. Release of tumor necrosis
factor alpha (TNF-α) and interleukin-6 (IL-6) from dysfunctional
adipocytes may drive hepatocyte apoptosis to start
the process. Bile stasis is unlikely with NAFLD, and jaundice
is not a key feature. Hemosiderin deposition is a function of
iron absorption from diet or genetics.

Question 33

31 A study of persons with increased risk for ischemic heart
disease reveals that some of them also have liver disease. Risk
factors include lack of exercise and increased consumption of
fast-food products containing high fructose corn syrup. Laboratory
studies show that their blood glucose averages 117 mg/
dL. Serum AST and ALT are elevated. Abdominal CT imaging
shows hepatomegaly with diffusely decreased attenuation but
no focal lesions. Some of them go on to develop hepatocellular
adenoma. Which of the following underlying disorders do
these persons most likely have?
A Type 1 diabetes mellitus
B Familial hypercholesterolemia
C Hepatitis C virus infection
D Hereditary hemochromatosis
E Metabolic syndrome

Answer 33

31 E Nonalcoholic fatty liver disease (NAFLD) may progress
to nonalcoholic steatohepatitis (NASH) and even to
cirrhosis. Risk factors of metabolic syndrome and type 2
diabetes mellitus are driven by obesity. NAFLD may be
found in a third of adults, closely paralleling the prevalence
of obesity. Pathologic features with NAFLD and NASH are
similar to those of alcoholic liver disease. Type 1 diabetes
mellitus leads to a catabolic state with weight loss. Familial
hypercholesterolemia mainly drives atherosclerosis, without
liver disease. Chronic viral hepatitis may have an element of
steatosis, but not marked, and without vascular disease. The
iron accumulation of hemochromatosis may produce cardiomyopathy
as well as chronic liver disease without much
steatosis.

Question 34

32 A 4-year-old girl has abrupt onset of vomiting, which
remains protracted for 24 hours. On arrival at the emergency
department, the child is lethargic and febrile to 37.7° C. The
parents state that she had a mild upper respiratory tract illness
3 days ago, but was improving, and the only medication
she received was acetylsalicylic acid (aspirin). On physical
examination, there is poor skin turgor, the lungs are clear, the
abdomen is nontender, and the heart rate is regular. Laboratory
findings show Na+, 150 mmol/L; K+, 4.5 mmol/L; Cl–,
93 mmol/L; CO2, 30 mmol/L; glucose, 60 mg/dL; creatinine,
1.1 mg/dL; amylase, 25 U/L; AST, 386 U/L; ALT, 409 U/L;
alkaline phosphatase, 120 U/L; total bilirubin, 1.1 mg/dL;
ammonia, 80 μmol/L; and prothrombin time, 26 seconds with
INR of 2. The child becomes comatose. What pathologic finding
is most likely present in the liver of this girl?
A Common bile duct atresia
B Hepatic vein thrombosis
C Hepatoblastoma
D Intrahepatic duct lithiasis
E Microvesicular steatosis
F Multinucleated giant cell hepatitis

Answer 34

32 E The microvesicular steatosis characteristic of Reye
syndrome rarely occurs now because the link between aspirin
use in children following a fever and hepatic injury has been recognized; it is caused by severe mitochondrial dysfunction
in the brain and liver. Biliary atresia with marked hyperbilirubinemia
becomes apparent in the neonatal period. Hepatic
venous thrombosis leads to Budd-Chiari syndrome, which
is typically a disease of adults that complicates such conditions
as polycythemia or pregnancy. Hepatoblastomas may
be congenital, but they are mass lesions unlikely to be associated
with such marked increases in liver enzymes. Intrahepatic
lithiasis is unlikely to occur in children and is unlikely
to produce marked increases in liver enzymes. Neonatal
giant cell hepatitis can produce findings of acute hepatitis in
neonates, not in children.

Question 35

33 A 23-year-old man has noted a yellow color to his sclerae
for the past 2 weeks. On physical examination he has generalized
jaundice. He has the physique of a bodybuilder. Laboratory
studies show serum total bilirubin, 5.6 mg/dL; ALT, 117
U/L; AST, 103 U/L; alkaline phosphatase, 148 U/L; albumin,
5.5 g/dL; and total protein, 7.9 g/dL. Which of the following
substances is he most likely to be using?
A Acetaminophen
B Anabolic steroid
C Chlorpromazine
D Ethyl alcohol
E Isoniazid

Answer 35

33 B Anabolic androgenic steroids are injected for the
purpose of increasing muscle mass to enhance athletic performance.
Because performance is primarily correlated with
skill and training, the potential gain from muscle mass is
problematic, particularly in view of the deleterious effects,
such as hepatic cholestatic hepatitis. Acetaminophen can
produce hepatic necrosis, but icterus is less likely. Chlorpromazine
is more likely to produce a pure cholestasis as an
idiosyncratic (unpredictable) reaction. Ethanol can produce
steatosis, and in excess the AST is often higher than the ALT.
Isoniazid may produce hepatic necrosis in persons treated
for tuberculosis.

Question 36

34 A 68-year-old woman has become increasingly tired,
with a 3-kg weight loss without dieting over the past
6 months. On physical examination a stool sample is positive
for occult blood. Laboratory studies show total serum protein,
6.1 g/dL; albumin, 3.9 g/dL; total bilirubin, 1.1 g/dL;
AST, 38 U/L; ALT, 44 U/L; alkaline phosphatase, 294 U/L;
glucose, 70 mg/dL; and creatinine, 0.9 mg/dL. CBC shows
hemoglobin, 8.9 g/dL; hematocrit, 26.7%; MCV, 75 μm3;
platelet count, 198,400/mm3; and WBC count, 5520/mm3. The prothrombin time is 13 seconds, and partial thromboplastin
time is 25 seconds. Serologic test results for HAV,
HBV, and HCV are negative. A chest radiograph shows no
abnormal findings. What is the most likely diagnosis?
A Antiphospholipid syndrome
B Ascending cholangitis
C Chronic alcoholism
D Metastatic adenocarcinoma
E Sclerosing cholangitis

Answer 36

34 D An elevated alkaline phosphatase level suggests
obstruction of the biliary tract, but this case must be focal
because the bilirubin is not elevated. The microcytic anemia
and the blood in the stool suggest gastrointestinal tract hemorrhage,
and a colonic adenocarcinoma should be suspected
as the primary site for the hepatic metastases in this case.
Hepatic metastases from colon cancer are common. They
appear as multiple masses within the hepatic parenchyma.
Antiphospholipid syndrome predisposes to thrombosis
with venous obstruction, in which case hepatic enzyme levels
should be higher, and the partial thromboplastin time
should be prolonged. Ascending cholangitis is typically
caused by bacteria such as Escherichia coli or Klebsiella, and
patients develop acute symptoms of fever, chills, jaundice,
and abdominal pain. Chronic alcoholism is not accompanied
by an increase in the alkaline phosphatase level, and there
is often a macrocytic anemia. Sclerosing cholangitis would
increase the bilirubin concentration and the alkaline phosphatase
level.

Question 37

35 A 20-year-old primigravida gives birth at term following
an uncomplicated pregnancy to a boy infant of normal weight
and length. On examination no abnormalities are noted.
Within the first week, the infant becomes mildly icteric. The
infant receives phototherapy, and there is no more icterus after
the second week of life. Which of the following mechanisms
most likely led to this infant’s icterus?
A Atresia of the common bile duct
B Congenital infection with cytomegalovirus
C Inherited deficiency of a canalicular transporter
D Low hepatic glucuronyl transferase activity
E Maternally derived antibody-mediated hemolysis

Answer 37

35 D This is neonatal physiologic jaundice that is mild and
transient and is due to diminished hepatic conjugating and
excreting capacity for bilirubin that is not fully functional until
2 weeks of life. Biliary atresia with obstruction produces more
severe jaundice and requires surgical intervention. Neonatal
hepatitis can be due to congenital infections that produce
more severe jaundice that persists more than 2 weeks. The rare
Dubin-Johnson syndrome can occur with autosomal recessive
mutation of a gene encoding a canalicular transporter protein that impairs bilirubin excretion. Erythroblastosis fetalis from
maternal sensitization to fetal RBC antigens is unlikely to
affect the first pregnancy

Question 38

36 A 35-year-old woman has noticed an increasing yellowish
hue to her skin for the past week. On physical examination,
there is no abdominal pain or tenderness, and the
liver span is normal. Laboratory findings include hemoglobin,
11.7 g/dL; hematocrit, 35.2%; MCV, 98 μm3; platelet
count, 207,600/mm3; WBC count, 6360/mm3; total protein,
5.5 g5/dL; albumin, 3.5 g/dL; total bilirubin, 8.7 mg/dL;
direct bilirubin, 0.6 mg/dL; AST, 39 U/L; ALT, 24 U/L;
and alkaline phosphatase, 35 U/L. What is the most likely
diagnosis?
A Cholelithiasis
B Hemolytic anemia
C Hepatitis A viral infection
D Micronodular cirrhosis
E Oral contraceptive use

Answer 38

36 B An unconjugated hyperbilirubinemia can result
from hemolysis. With increased RBC destruction, there is
more bilirubin than can be conjugated by the hepatocytes.
Obstructive jaundice with biliary tract lithiasis results in
mostly conjugated hyperbilirubinemia. The total bilirubin
concentration may be increased in patients with viral hepatitis
or cirrhosis and in individuals taking drugs such as
oral contraceptives. Although direct and indirect hyperbilirubinemia
may occur in these conditions, conjugated
hyperbilirubinemia predominates.

Question 39

37 A 25-year-old medical student from Mozambique notices
that his sclerae have a slight yellowish color on the day of the
final examination. He has never had a major illness. On physical
examination, there are no significant findings other than the
mild scleral icterus. Laboratory studies show total serum protein,
7.9 g/dL; albumin, 4.8 g/dL; AST, 48 U/L; ALT, 19 U/L; alkaline
phosphatase, 32 U/L; total bilirubin, 4.9 mg/dL; and direct
bilirubin, 0.8 mg/dL. The scleral icterus resolves within 2 days.
Which of the following conditions is he most likely to have?
A Acetaminophen ingestion
B Choledochal cyst
C Dubin-Johnson syndrome
D Gilbert syndrome
E Hepatitis A virus infection
F Primary biliary cirrhosis

Answer 39

37 D Gilbert syndrome results from decreased levels of
uridine diphosphate glucuronosyltransferase (UDPGT),
which may be the status of 3% to 7% of the general population
of the United States. Lower levels are more common in
Africa but less frequent in Asia. The condition is often never
diagnosed. Stress may cause transient unconjugated hyperbilirubinemia
to a point that scleral icterus is detectable, when the
serum bilirubin reaches about 2 to 2.5 mg/dL. Acetaminophen
in small quantities can be properly detoxified, but ingestion of
large quantities can produce hepatocyte necrosis. Choledochal
cyst is a rare congenital anomaly producing extrahepatic biliary
obstruction with conjugated hyperbilirubinemia. Primary
biliary cirrhosis results in conjugated hyperbilirubinemia, as
does the rare Dubin-Johnson syndrome. HAV infection can
often be mild, but it is not so transient; it can be accompanied
by a mild increase in conjugated and unconjugated bilirubin.

Question 40

38 A 42-year-old woman from Lisbon, Portugal, has had
fever, chills, and bouts of colicky right upper quadrant pain
for the past week. On physical examination, her skin is icteric,
and there is scleral icterus. Laboratory studies show a total
serum bilirubin concentration of 7.1 mg/dL and direct bilirubin
concentration of 6.7 mg/dL. An abdominal ultrasound
scan shows cholelithiasis; dilation of the common bile duct;
and two cystic lesions, 0.8 cm and 1.5 cm, in the right lobe
of the liver. Which of the following infectious agents is most
likely to produce these findings?
A Clonorchis sinensis
B Cryptosporidium parvum
C Cytomegalovirus
D Entamoeba histolytica
E Escherichia coli

Answer 40

38 E This patient has a history of gallstones and has
developed an ascending cholangitis caused by Escherichia
coli. These bacteria reach the liver by ascending the biliary
tree. Obstruction from lithiasis is the most common risk factor.
Development of cystic lesions in the right lobe of the
liver suggests that the patient has developed liver abscesses.
Clonorchis sinensis is a liver fluke that is endemic to East Asia,
and it is a risk factor for biliary tract cancer. Cryptosporidiosis
in immunocompromised patients occasionally can occur
in the biliary tract and elsewhere. Cytomegalovirus infection
also can be seen in immunocompromised patients; it produces
a clinical picture similar to that of hepatitis, but without
biliary tract disease. A patient with amebiasis involving
the liver is most likely to present with a history of diarrhea
with blood and mucus.

Question 41

39 A 17-year-old woman, G2, P1, gives birth to a term infant
after an uncomplicated pregnancy. The infant does well for 3
weeks, but then begins to have abdominal enlargement, lightcolored
stools, and dark urine. On physical examination, the
infant is icteric. There is hepatomegaly, but no splenomegaly
or lymphadenopathy. Laboratory studies show serum AST of
101 U/L, ALT of 123 U/L, alkaline phosphatase 20 U/L, glucose
of 81 mg/dL, and creatinine of 0.4 mg/dL. A liver biopsy
is done, and microscopically shows lobular disarray with focal
hepatocyte necrosis, giant cell transformation, cholestasis,
portal mononuclear cell infiltrates, Kupffer cell hyperplasia,
and extramedullary hematopoiesis. What is the most likely
diagnosis?
A Erythroblastosis fetalis
B Extrahepatic biliary atresia
C Galactosemia
D Idiopathic neonatal hepatitis
E Primary biliary cirrhosis
F Von Gierke disease

Answer 41

39 D Neonatal cholestasis is newborn jaundice that persists
more than 2 weeks following birth. One cause is neonatal
hepatitis, which is most often idiopathic, and most infants
recover without specific therapy. Some cases are caused by
α1-antitrypsin deficiency, and some are due to extrahepatic biliary atresia. Patients with extrahepatic biliary atresia will
have a high alkaline phosphatase and require surgery to
anastomose extrahepatic ducts and prevent progressive
liver damage. Patients with erythroblastosis fetalis have
hydrops and icterus at birth because of maternal IgG antibody
directed at fetal RBCs, leading to hemolysis. Galactosemia
is an inborn error of metabolism in which deficiency
of galactose-1-phosphate uridylyltransferase damages cells
of the kidney, liver, and brain; there is hepatomegaly, splenomegaly,
hypoglycemia, and eventually cirrhosis. Primary
biliary cirrhosis affects adults. Von Gierke disease results
from deficiency of glucose-6-phosphatase, and affected
infants develop hypoglycemia, lactic acidosis, hyperuricemia,
and hyperlipidemia.

Question 42

40 A 19-year-old mother notices that her 3-week-old neonate
has increasing jaundice. The pregnancy was uncomplicated
and ended in a normal term birth. On physical
examination, the infant now exhibits generalized jaundice,
hepatomegaly, and acholic stool. Laboratory studies show
total serum bilirubin of 10.1 mg/dL, AST of 123 U/L, ALT of
140 U/L, glucose of 77 mg/dL, and creatinine of 0.4 mg/dL.
The alkaline phosphatase is normal. A liver biopsy is done
and microscopically shows marked proliferation of bile
ducts, portal tract edema and fibrosis, and extensive intrahepatic
and canalicular bile stasis. The infant develops progressively
worsening jaundice and dies of liver failure at 9 months
of age. What is the most likely diagnosis?
A α1-Antitrypsin deficiency
B Choledochal cyst
C Congenital toxoplasmosis
D Extrahepatic biliary atresia
E Hepatoblastoma

Answer 42

40 D Extrahepatic biliary atresia is a rare condition in which
some or all of the bile ducts are destroyed. If the disease spares
a large enough bile duct to anastomose around the obstruction,
the problem may be correctable. In many cases, such as this
one, obstruction of bile ducts occurs above the porta hepatis,
however, and the only option for treatment is liver transplantation.
α1-Antitrypsin deficiency can produce a neonatal hepatitis
that may clinically resemble extrahepatic biliary atresia, but
most infants recover. A choledochal cyst may cause biliary colic
in children; it is a congenital condition that produces dilations
of the common bile duct. Congenital infections may involve the
liver, and usually other organs as well; infants with these infections
are ill from birth. Hepatoblastomas are rare and may be
seen in infancy, but mass lesions in the hepatic parenchyma
typically do not obstruct the biliary tree completely

Question 43

41 A 45-year-old woman has had increasing pruritus and
icterus for 7 months. On physical examination, she has generalized
jaundice. Laboratory studies show total serum protein,
6.3 g/dL; albumin, 2.7 g/dL; total bilirubin, 5.7 mg/dL; direct
bilirubin, 4.6 mg/dL; AST, 77 U/L; ALT, 81 U/L; and alkaline
phosphatase, 221 U/L. A liver biopsy specimen shows destruction of portal tracts, loss of bile ducts, and lymphocytic
infiltrates. Which of the following additional laboratory findings
is most likely to be present in this woman?
A Decreased α1-antitrypsin level
B Elevated sweat chloride level
C Increased serum ferritin level
D Positive anti-HCV
E Positive antimitochondrial antibody

Answer 43

41 E Primary biliary cirrhosis is an uncommon autoimmune
disorder that causes progressive intrahepatic bile
duct destruction. Pruritus, conjugated hyperbilirubinemia,
and increased alkaline phosphatase levels are indicative
of obstructive jaundice resulting from bile duct destruction.
About 90% or more of patients with this disease have
antimitochondrial antibodies in the serum. α1-Antitrypsin
deficiency can affect the liver, causing chronic hepatitis and
cirrhosis, and causes panlobular emphysema. An elevated
sweat chloride level is found in cystic fibrosis, which can
cause neonatal jaundice. An increased serum ferritin level is
seen in patients with hereditary hemochromatosis. Chronic
hepatitis C is marked by hepatocyte necrosis, not by bile duct
destruction.

Question 44

42 A 43-year-old man has experienced progressive
fatigue, pruritus, and icterus for 4 months. A colectomy was
performed 5 years ago for treatment of ulcerative colitis.
On physical examination, he now has generalized jaundice.
The abdomen is not distended; on palpation, there is no
abdominal pain and there are no masses. Laboratory studies
show a serum alkaline phosphatase level of 285 U/L and
an elevated titer of anti–neutrophil cytoplasmic antibodies.
Cholangiography shows widespread intrahepatic biliary
tree obliteration and a beaded appearance in the remaining
ducts. Which of the following morphologic features is most
likely to be present in his liver?
A Concentric “onion-skin” ductular fibrosis
B Copper deposition in hepatocytes
C Granulomatous bile duct destruction
D Interface hepatitis
E Periportal PAS-positive globules
F Portal bridging fibrosis

Answer 44

42 A The major targets in primary sclerosing cholangitis
are intrahepatic bile ducts, and ulcerative colitis coexists in
70% of cases. Ducts undergo a destructive cholangitis that
leads eventually to periductal fibrosis and cholestatic jaundice.
Eventually, cirrhosis and liver failure can occur. Copper
deposition is characteristic of Wilson disease, which is
associated with chronic hepatitis and cirrhosis. Granulomatous
bile duct destruction occurs in primary biliary cirrhosis.
Interface hepatitis is characteristic of chronic active viral hepatitis. α1-Antitrypsin deficiency with PAS-positive periportal
globules is associated with cirrhosis. Portal bridging
fibrosis with nodular regeneration defines cirrhosis.

Question 45

43 A 44-year-old man has had increasing arthritis pain,
swelling of the feet, and reduced exercise tolerance over the
past 3 years. Laboratory studies include serum glucose of 201
mg/dL, creatinine of 1.1 mg/dL, and ferritin of 893 ng/mL.
A chest radiograph shows bilateral pleural effusions, pulmonary
edema, and cardiomegaly. He undergoes a liver biopsy;
the microscopic appearance of a biopsy specimen stained with
H&E (right panel) and Prussian blue (left panel) is shown in the
figure. Based on these findings, which of the following is the
most appropriate therapy for this patient?
A Cholecystectomy
B Interferon-α
C Phlebotomy
D Prednisone
E Reduce alcohol intake

Answer 45

43 C This patient has clinical, histologic, and laboratory features
of genetic hemochromatosis. In this condition, iron overload
occurs because of excessive absorption of dietary iron.
The absorbed iron is deposited in many tissues, including the
heart, pancreas, and liver, giving rise to heart failure, diabetes,
and cirrhosis. It appears blue with Prussian blue stain, as seen
in this figure. High serum ferritin concentration is an indicator
of a vast increase in body iron. Genetic hemochromatosis is an
autosomal recessive condition; siblings are at risk of developing
the same disease. Phlebotomy removes 250 mg of iron per
unit of blood, and over time can reduce iron stores.

Question 46

44 A 46-year-old man has had gradually increasing
abdominal distention along with decreased libido for the
past 7 months. Physical examination reveals excessive skin
pigmentation in sun-exposed areas. He has an abdominal
fluid wave and modest splenomegaly. Fasting serum laboratory
findings include glucose, 200 mg/dL; creatinine, 0.8 g/
dL; ferritin, 650 ng/mL; total protein, 6.3 g/dL; and albumin,
2.2 g/dL. His total bilirubin, AST, ALT, and alkaline phosphatase
values are normal. Hemoglobin is 13.5 g/dL, hematocrit
is 40.6%, MCV is 94 μm3, platelet count is 200,000/mm3, and
WBC count is 6570/mm3. His prothrombin time is 20 seconds,
and partial thromboplastin time is 65 seconds. A mutation in
a gene leading to which of the following molecular abnormalities
most likely explains his disease?
A β2-Microglobulin gene, preventing the binding of
β2-microglobulin to HFE
B β-Globin gene, with ineffective erythropoiesis and
excessive absorption of iron
C Divalent metal transporter 1 gene, causing
increased binding to intestinal luminal iron
D HFE gene, reducing hepcidin synthesis and
increasing iron absorption
E Transferrin gene, with sequestration of iron in the
liver

Answer 46

44 D This patient has hereditary hemochromatosis from
excessive iron storage leading to ascites, splenomegaly,
impaired liver function, diabetes mellitus, skin pigmentation,
and elevated ferritin. Because he has no predisposing causes
for increased iron absorption, the most likely diagnosis is
primary, or genetic, hemochromatosis. This disease results
from a mutation in the HFE gene that encodes for an HLA
class I–like molecule that binds β2-microglobulin. Mutant
HFE reduces hepcidin synthesis to decrease circulating hepcidin.
The resulting decreased hepcidin-ferroportin interaction
allows for increased ferroportin activity, increased iron
efflux from enterocytes, giving rise to systemic iron overload
in hereditary hemochromatosis. Because this patient is not
anemic and has a normal MCV, a β-globin gene mutation
with β-thalassemia is unlikely. None of the other listed mutations
affect iron absorption.

Question 47

45 A 23-year-old man has had worsening congestive heart
failure along with arthritis resembling pseudogout for the past
6 years. On examination his skin has a slate-grey color, his
heart rate is irregular, his liver span is increased, and the spleen
is palpable. Both testes appear small and atrophic. Laboratory
studies show an elevated hemoglobin A1c and increased serum
ferritin. A mutation involving which of the following genes is
most likely to be present in this woman?
A MHC Class I
B ATP7B
C HAMP
D HNF1-α
E DMT1

Answer 47

45 C Although most cases of hereditary hemochromatosis
result from mutations of the HFE gene, some cases may occur
from mutations of genes encoding for transferrin receptors,
hemojuvelin, and rarely hepcidin (encoded by the HAMP
gene). However, the main regulator of iron absorption is
the protein hepcidin and all the genetic causes of hereditary
hemochromatosis are associated with reduced hepcidin levels.
Mutations in the HAMP gene produce extremely severe disease
at an early age (Juvenile hemochromatosis) with cardiomyopathy
and hypogonadism. Ordinarily the liver increases
hepcidin production when iron stores are adequate, preventing
release of iron from intestinal enterocytes and macrophages.
MHC Class 1 proteins are involved in peptide antigen recognition
for T-cell mediated immunity. ATP7B gene mutations are
present with Wilson disease, a disorder of copper metabolism.
Mutations of HNF1-α are seen with maturity onset diabetes of
the young (MODY) and can lead to the appearance of hepatic
adenomas. DMT1 is involved in enterocyte iron absorption.

Question 48

46 A 19-year-old woman is bothered by a tremor at rest,
which becomes progressively worse over the next 6 months.
She exhibits paranoid ideation with auditory hallucinations
and is diagnosed with an acute psychosis. On physical examination,
she has scleral icterus. A slit lamp examination shows
corneal Kayser-Fleischer rings. Laboratory findings include
total serum protein, 5.9 g/dL; albumin, 3.1 g/dL; total bilirubin,
4.9 mg/dL; direct bilirubin, 3.1 mg/dL; AST, 128 U/L;
ALT, 157 U/L; and alkaline phosphatase, 56 U/L. Which of
the following additional serologic test findings is most likely
to be reported in this patient?
A Decreased α1-antitrypsin level
B Decreased ceruloplasmin level
C Increased α-fetoprotein level
D Increased ferritin level
E Positive antimitochondrial antibody
F Positive HbsAg

Answer 48

46 B Wilson disease is an inherited disorder in which
toxic levels of copper accumulate in tissues, particularly the brain, eye, and liver. The ATP7B gene for Wilson disease
encodes a copper-transporting ATPase in the hepatocytes.
With mutations in this gene, copper cannot be secreted into
plasma. Ceruloplasmin is an α2-globulin that carries copper
in plasma. Because copper cannot be secreted into plasma,
ceruloplasmin levels are low. Chronic liver disease and panlobular
emphysema may occur in α1-antitrypsin deficiency.
An increased α-fetoprotein is a marker for hepatocellular carcinoma.
An increased serum ferritin may indicate hereditary
hemochromatosis. A positive finding for antimitochondrial
antibody can be seen in primary biliary cirrhosis. A positive
HBsAg result indicates HBV, which infects only the liver.

Question 49

47 A 28-year-old man has had increasing shortness of
breath for the past year. On physical examination, he is afebrile
and normotensive. Breath sounds are decreased in all
lung fields. His medical history indicates that he developed
marked icterus as a neonate, but he has been healthy since
then. There is a family history of liver disease. A liver biopsy is
performed, and the figure shows the microscopic appearance
stained with PAS. This patient is most likely at a very high risk
for development of which of the following conditions?
A Acute fulminant hepatitis
B Diabetes mellitus
C Pulmonary emphysema
D Systemic lupus erythematosus
E Ulcerative colitis

Answer 49

47 C The PAS-positive globules in the liver seen here are
characteristic of α1-antitrypsin (AAT) deficiency. Approximately
10% of individuals with the homozygous deficiency
(PiZZ phenotype) of AAT deficiency develop significant
liver disease, including neonatal hepatitis and progressive
cirrhosis. Deficiency of AAT also allows unchecked action of
elastases in the lung, which destroys the elastic tissue and
causes emphysema. AAT can produce a picture of chronic
hepatitis in adults; it can lead to neonatal hepatitis with acute
but often transient liver injury. Diabetes mellitus and heart
failure are features of hemochromatosis, a condition of iron
overload. Iron deposition in liver is detected by the Prussian
blue stain. Systemic lupus erythematosus is an immune complex
disease that may affect many organs. Liver involvement
is uncommon, however. Ulcerative colitis is strongly associated
with primary sclerosing cholangitis, a condition in
which there is inflammation and obliterative fibrosis of bile
ducts.

Question 50

48 A 39-year-old woman has had increasing abdominal
girth for a month, then pain for the past day. On physical
examination there is hepatomegaly and caput medusae. Laboratory
studies show Hgb, 20.5 g/dL; Hct, 61.7%; platelet
count, 411,000/mm3; AST, 333 U/L; and ALT, 358 U/L. What
is ultrasonography of her abdomen most likely to show?
A Choledocholithiasis
B Cirrhosis
C Hepatic vein thrombosis
D Hepatocellular carcinoma
E Macrovesicular steatosis
F Subphrenic abscess

Answer 50

48 C This is Budd-Chiari syndrome, which results from
hepatic venous outflow obstruction. The high hemoglobin
and platelet count in this woman is consistent with polycythemia
vera as part of a myeloproliferative disorder, and
this is the likely cause. Choledocholithiasis should lead to
jaundice. Cirrhosis may also lead to caput medusae and
increasing girth from ascites, but polycythemia is not seen
with cirrhosis. Some hepatocellular carcinomas, arising in
the setting of cirrhosis, may produce Budd-Chiari syndrome,
but there is no polycythemia. Fatty change alone does not
produce hepatic outflow obstruction. An abscess below the
diaphragm is unlikely to impinge upon the hepatic vein.

Question 51

49 A 50-year-old man has increasing dyspnea with idiopathic
pulmonary fibrosis, which was diagnosed 18 months
ago. Physical examination shows elevated jugular venous
pressure and pedal edema. Laboratory studies show serum
AST of 221 U/L, ALT of 234 U/L, alkaline phosphatase of 48
U/L, lactate dehydrogenase of 710 U/L, total bilirubin of 1.2
mg/dL, albumin of 3.5 g/dL, and total protein of 5.4 g/dL.
The figure shows the microscopic appearance of a liver biopsy
specimen. Which of the following terms best describes these
findings?
A Apoptosis
B Centrilobular congestion
C Cholestasis
D Hemosiderin deposition
E Macrovesicular steatosis
F Mallory-Denk bodies
G Portal fibrosis

Answer 51

49 B The microscopic appearance is that of intense centrilobular
congestion. The area around the portal tract is less
congested. The restrictive lung disease leads to cor pulmonale
with right-sided congestive heart failure. This causes passive
venous congestion in the liver that is most pronounced
in the centrilobular areas. When congestion is severe, the
anoxia can cause centrilobular necrosis with transaminase
elevation. Apoptosis does not produce widespread necrosis
because single cells are involved, and this is most typical of
viral hepatitis. Cholestasis is marked by plugs of yellowgreen
bile in canaliculi. Hemosiderin appears granular and brown on H&E staining, but it is blue with Prussian blue
stain. Large lipid droplets fill the hepatocyte cytoplasm with
macrovesicular steatosis. Mallory bodies are globular red
cytoplasmic structures most characteristic of alcoholism, in
particular, acute alcoholic hepatitis. Portal fibrosis begins the
process of cirrhosis.

Question 52

50 A 26-year-old primigravida in the third trimester has had
worsening peripheral edema for the past month. On examination,
she is afebrile, but her blood pressure is 165/105 mm Hg.
She has pitting edema to her thighs. Laboratory studies show
hemoglobin, 11.7 g/dL; platelet count, 46,000/mm3; WBC
count, 7210/mm3; albumin, 3.2 g/dL; total protein, 5.8 g/dL;
total bilirubin, 1.2 mg/dL; AST, 208 U/L; ALT, 241 U/L; alkaline
phosphatase, 32 U/L; and haptoglobin, 5 mg/dL. Urinalysis
shows 4+ proteinuria, but no glucosuria. Her prothrombin
time is 30 seconds. What is the best treatment for her condition?
A Corticosteroids
B Intravenous immunoglobulin
C Liver transplantation
D Plasmapheresis
E Pregnancy termination
F Portacaval shunt
G Ribavirin and interferon

Answer 52

50 E She has maternal HELLP syndrome (hemolysis, elevated
liver enzymes, and low platelets), which is a severe
complication of preeclampsia, and when a coagulopathy is
apparent from the increasing prothrombin time, emergent
delivery must be undertaken to save the life of the mother
and fetus. Corticosteroid therapy is used for inflammatory
conditions, typically those that have an autoimmune basis.
Intravenous immunoglobulin may aid in treating infections,
such as hepatitis B immunoglobulin. Liver transplantation is
indicated with liver failure from which no potential recovery
is possible. Plasmapheresis aids in treating conditions such
as thrombotic thrombocytopenic purpura, which have circulating
antibodies, proteins, or toxins that can be removed
emergently. Portacaval shunt is used to treat cirrhosis with
hepatic encephalopathy. Ribavirin and interferon therapy is
used for viral hepatitis C infection.

Question 53

51 A 28-year-old woman, G3, P2, is in the 35th week of a
previously uncomplicated pregnancy when she develops
increasing lethargy with nausea, vomiting, and jaundice over
a 10-day period. On physical examination, she has generalized
jaundice and scattered ecchymoses over the trunk and
extremities. Laboratory studies show total serum bilirubin of
5.8 mg/dL, AST of 122 U/L, ALT of 131 U/L, and alkaline
phosphatase of 125 U/L. Which of the following histologic
features is most likely to be found in a liver biopsy specimen?
A Concentric bile duct fibrosis
B Extensive intrahepatic hemosiderin deposition
C Inflammation with loss of intrahepatic bile ducts
D Marked microvesicular steatosis
E Multinucleated giant cells
F Periportal PAS-positive hepatic globules

Answer 53

51 D She has acute fatty liver of pregnancy, an uncommon
condition of variable severity. Accumulation of small
droplets of fat in hepatocytes (microvesicular steatosis) is the
typical histologic finding. This feature is not seen in any of
the other conditions listed. The disease may occur because
of a defect in intramitochondrial fatty acid oxidation. Concentric
bile duct fibrosis is a feature of sclerosing cholangitis.
Hereditary hemochromatosis manifests with complications
in middle age after extensive iron deposition has occurred.
Extrahepatic biliary atresia is a rare neonatal disease. The loss
of intrahepatic bile ducts in primary biliary cirrhosis also is
a rare disease of middle age. Multinucleated giant cells may
be seen in neonatal giant cell hepatitis. PAS-positive globules
are seen in αl-antitrypsin deficiency, a condition that affects
adults.

Question 54

52 A 41-year-old, previously healthy woman has noted
abdominal discomfort for the past month. Laboratory studies
show normal serum total protein, albumin, AST, ALT, and
bilirubin, but her alkaline phosphatase level is elevated.
Serologic testing for hepatitis A, B, and C viruses is negative.
Abdominal CT scan shows a 9-cm right hepatic lobe mass
with irregular borders. The lesion is resected, and gross
inspection reveals a central stellate scar with radiating fibrous
septa that merge into surrounding hepatic parenchyma. On
microscopic examination, the mass has prominent arteries in
dense connective tissue along with lymphocytic infiltrates
and bile duct proliferation. What is the most likely diagnosis?
A Cholangiocarcinoma
B Focal nodular hyperplasia
C Hepatic adenoma
D Hepatocellular carcinoma
E Macronodular cirrhosis
F Metastatic adenocarcinoma

Answer 54

52 B Focal nodular hyperplasia is a well-demarcated
but unencapsulated benign lesion that is characterized by a
central scar. Cholangiocarcinomas have extensive collagen
deposition, but are malignant and often associated with risk
factors including viral hepatitis. Hepatic adenomas can be
seen with oral contraceptive use. Hepatocellular carcinomas
occur after liver injury from such conditions as viral hepatitis
or alcohol abuse, and they often can be multifocal. Cirrhosis
involves the entire liver, not just a portion. Metastases can be
solitary or multiple and can have central necrosis when large.

Question 55

53 A 36-year-old woman is in the sixth month of her first
pregnancy, but she is unsure of her dates because she was
taking oral contraceptives at the time she became pregnant.
She experiences sudden onset of severe abdominal pain. On
physical examination, she is afebrile and normotensive. There
is right upper quadrant tenderness on palpation. An ultrasound
scan of the abdomen shows a well-circumscribed, 7-cm
subcapsular hepatic mass. Paracentesis yields bloody fluid. At
laparotomy, the mass in the right hepatic lower lobe, which
has ruptured through the liver capsule, is removed. The
remaining liver parenchyma appears to be of uniform consistency,
and the liver capsule is otherwise smooth. Which of the
following is the most likely diagnosis?
A Cholangiocarcinoma
B Choledochal cyst
C Choriocarcinoma
D Focal nodular hyperplasia
E Hepatic adenoma
F Hepatoblastoma
G Hepatocellular carcinoma

Answer 55

53 E The circumscribed mass in the liver suggests a benign
tumor, such as hepatic adenoma. These tumors, which may develop in young women who have used oral contraceptives,
can enlarge and rupture from estrogenic stimulation
during pregnancy. These adenomas may have HFN1-α or
β-catenin gene mutations. Cholangiocarcinomas and hepatocellular
carcinomas can be related to viral hepatitis infection
and alcoholism; they are large, irregular masses that tend
to occur in patients who are older than this woman. Choledochal
cysts of the biliary tract are rare embryonic remnants
that typically become symptomatic in childhood, along with
biliary colic. Molar pregnancy can include choriocarcinoma,
which can metastasize and rupture, but a solitary circumscribed
metastasis is unlikely. Hepatoblastomas are rare
liver neoplasms found in children.

Question 56

54 A 79-year-old man has had increasing abdominal discomfort
and malaise for the past year. On physical examination
his liver span is increased. His stool is positive for occult
blood. Laboratory studies show Hgb, 8 g/dL; Hct, 22%; MCV,
72 μm3; total protein, 5.6 g/dL; albumin, 3.7 g/dL; and alkaline
phosphatase, 209 U/L. The representative appearance of
his liver is shown in the figure. Which of the following underlying
conditions is he most likely to have?
A Chronic alcohol abuse
B Colonic adenocarcinoma
C Gilbert syndrome
D Hepatitis B virus infection
E Metabolic syndrome

Answer 56

54 B Multiple masses shown in the figure are consistent
with metastatic carcinoma. Metastases in liver are far more
common than primary liver neoplasms. The microcytic
anemia and the stool positive for occult blood suggest colon
cancer. Mass lesions cause intrahepatic biliary obstruction
to elevate the alkaline phosphatase. The hepatic parenchyma
has a rich vascular supply that makes it a target for
hematogenous spread of malignancies. Cirrhosis and the
potential for primary hepatocellular carcinoma may ensue
from either alcohol abuse or viral hepatitis B, but there is
likely a dominant mass lesion. Gilbert syndrome and other
hereditary hyperbilirubinemias are unlikely to lead to
malignancies. Metabolic syndrome and diabetes mellitus
increase the risk for NAFLD, NASH, cirrhosis, and hepatocellular
carcinoma.

Question 57

55 A clinical study of patients with cirrhosis includes MR
imaging. Patients with an intrahepatic nodule larger than 2 cm
that has arterial blood flow are found to be at increased risk for
hepatocellular carcinoma. Which of the following pathologic
findings is most likely to characterize these nodules?
A Adenoma
B Dysplasia
C Regeneration
D Siderosis
E Steatosis

Answer 57

55 B Dysplastic nodules are precursors to hepatocellular
carcinomas. Regenerative nodules as part of cirrhosis tend
to be smaller than 2 cm, and often smaller than 1 cm, with
portal venous blood supply. As dysplasia progresses to a
high-grade level, there is increased angiogenesis with arterialization.
Hepatic adenomas tend not to undergo malignant
transformation. Siderotic nodules may occur with hemochromatosis.
Steatosis is a feature of many hepatic diseases,
and is not a premalignant finding.

Question 58

56 A 38-year-old man from Shanghai, China, has experienced
fatigue and a 10-kg weight loss over the past 3 months.
Physical examination yields no remarkable findings. Laboratory
test results are positive for HBsAg and negative for anti-
HCV and anti-HAV. Abdominal CT scan shows a 10-cm solid
mass in the left lobe of a nodular liver. A liver biopsy of the
lesion is obtained and microscopically shows hepatocellular
carcinoma. Which of the following is most likely responsible
for the development of this lesion?
A Co-infection with Clonorchis sinensis
B Development of hepatic adenoma that accumulates
mutations
C Insertion of viral DNA in the vicinity of the NMYC
oncogene
D Inherited mutation in the DNA mismatch repair genes
E Ongoing infection with liver cell necrosis and
regeneration

Answer 58

56 E There is a long-term risk of hepatocellular carcinoma
in patients infected with HBV. This infection is more
common (often from vertical transmission) in Asia than in
North America and Europe, and it accounts for more cases
of primary liver cancer worldwide than other causes, such
as chronic alcoholism. HBV does not encode any oncogene,
and it does not integrate next to a known oncogene, such
as NMYC. Most likely, neoplastic transformation occurs
because HBV induces repeated cycles of liver cell death
and regeneration. This repeated cycling increases the risk
of accumulating mutations during several rounds of cell
division. Infection with the liver fluke Clonorchis sinensis
predisposes to bile duct carcinoma. In contrast to colon carcinomas,
hepatic carcinomas are not known to develop from adenomas. Hereditary nonpolyposis colon carcinoma syndrome
is associated with inherited DNA mismatch repair
genes

Question 59

57 A 41-year-old woman experienced increasing malaise
and a 10-kg weight loss in the past year. She becomes
increasingly obtunded and lapses into a coma. Her serum
α-fetoprotein is increased. The representative gross appearance
of her liver is shown in the figure. Ingestion of which of
the following substances is most likely to have played a role in
the development of this condition?
A Acetaminophen
B Aflatoxin
C Aspirin
D Ferrous sulfate
E Nitrites
F Raw oysters

Answer 59

57 B Aflatoxin is a hepatotoxin and is the product of the
fungus Aspergillus flavus, which grows on moldy cereals.
Aflatoxin can be carcinogenic, leading to hepatocellular carcinoma,
as shown in the figure. Ingestion of large amounts
of acetaminophen leads to hepatocellular necrosis. Aspirin
has been implicated in causing Reye syndrome in children,
which results in extensive microvesicular steatosis. Prolonged
and excessive intake of oral iron rarely can cause secondary
hemochromatosis. Nitrites have been causally linked
with cancers in the upper gastrointestinal tract. Oysters can
concentrate hepatitis A virus (HAV) from seawater contaminated
with sewage, and eating raw oysters can result in HAV
infection.

Question 60

58 A 36-year-old woman has become increasingly icteric
for 1 month. She has had several bouts of colicky, midabdominal
pain for 3 years. On physical examination, she has
generalized jaundice with scleral icterus. Her BMI is 32. There
is tenderness in the right upper quadrant, and the liver span
is normal. A liver biopsy is obtained, and microscopic examination
shows bile duct proliferation and intracanalicular bile
stasis, but no inflammation or hepatocyte necrosis. The level
of which of the following is most likely to be increased in the
patient’s serum?
A Alkaline phosphatase
B Ammonia
C Antimitochondrial antibody
D Hepatitis C antibody
E Indirect bilirubin level

Answer 60

58 A The findings suggest obstructive jaundice from
biliary tract disease (e.g., gallstones). Elevation of the
serum alkaline phosphatase level is characteristic of cholestasis
from biliary obstruction. The alkaline phosphatase
comes from bile duct epithelium and hepatocyte
canalicular membrane. The blood ammonia concentration
increases with worsening liver failure. When hepatic
failure is sufficient to cause hyperammonemia, mental
obtundation is seen. In this case, the patient has only
jaundice. Primary biliary cirrhosis with an increased antimitochondrial
antibody titer is much less common, and
PBD eventually leads to bile duct destruction. Most cases
of active HCV infection are accompanied by some degree
of inflammation with fibrosis. In obstructive biliary tract
disease, the direct bilirubin, not the indirect bilirubin,
should be elevated.

Question 61

59 A 34-year-old woman from Kobe, Japan, has experienced
intermittent upper abdominal pain for 3 weeks. Physical examination
yields no remarkable findings. Laboratory findings
show total serum protein of 7.3 g/dL, albumin of 5.2 g/dL,
total bilirubin of 7.5 mg/dL, direct bilirubin of 6.8 mg/dL, AST
of 35 U/L, ALT of 40 U/L, and alkaline phosphatase of 207
U/L. Representative microscopic findings in her liver include
intracanalicular cholestasis in the centrilobular regions, swollen
liver cells, and portal tract edema, but no necrosis and no
fibrosis. Which of the following underlying conditions is she
most likely to have?
A Cardiomyopathy
B Choledochal cyst
C Hemoglobinopathy
D Hepatitis B viral infection
E Ulcerative colitis
F Venoocclusive disease

Answer 61

59 B Intermittent upper abdominal pain, most often on the
right, is a nonspecific symptom that often occurs in patients
with gallstones. When a stone passes through the cystic duct
and into the common bile duct, or forms in the common duct,
intrahepatic cholestasis occurs. This explains the conjugated
hyperbilirubinemia and the increased alkaline phosphatase
level. Most reported cases of choledochal cyst, much less
common than gallstones, come from Japan; the biliary stasis
promotes infection with hydrolysis of bilirubin diglucuronides
to form brown stones. Chronic passive congestion
from heart failure does not typically produce hyperbilirubinemia.
Hemoglobinopathies with risk for hemolysis produce
mainly unconjugated hyperbilirubinemia. Active viral hepatitis
should be accompanied by some hepatocellular necrosis
with liver enzyme elevation. Ulcerative colitis is associated
with sclerosing cholangitis. Venoocclusive disease is rare
and is accompanied by hyperbilirubinemia and cholestasis,
but not by biliary tract obstruction.

Question 62

60 A 54-year-old First Nations woman has had colicky right
upper quadrant pain for the past week. She has nausea, but no
vomiting or diarrhea. On physical examination, she is afebrile.
There is marked tenderness of the right upper quadrant. The
liver span is normal. Her height is 160 cm (5 feet 3 inches), and
her weight is 90 kg (body mass index 33). An abdominal ultrasound
scan shows calculi within the lumen of the gallbladder,
and the gallbladder wall appears thickened. Intrahepatic and
extrahepatic bile ducts appear normal. The patient’s gallbladder
is removed by laparoscopic cholecystectomy; it has the appearance
shown in the figure. Which of the following mechanisms
is most likely to play the greatest role in development of her
disease?
A Antibody-mediated RBC lysis
B Ascaris lumbricoides within bile ducts
C Biliary hypersecretion of cholesterol
D Decreased renal excretion of phosphate
E Hepatocyte infection by HBV
F Ingestion of foods rich in fat
G Involvement of the terminal ileum by Crohn disease

Answer 62

60 C The figure shows cholesterol gallstones. These
stones are pale yellow, but acquire a variegated appearance
by trapping bile pigments. In comparison, pigment
stones are uniformly dark. Risk factors for such cholesterol
stones include Native American descent, female sex,
obesity, and increasing age. These factors cause secretion
of bile that is supersaturated in cholesterol. Patients
with RBC hemolysis develop pigment stones, whether the
hemolysis is antibody-mediated (autoimmune hemolytic
anemia), or whether it is caused by intrinsic RBC abnormalities
(hemoglobinopathies such as sickle cell anemia).
Infection of the biliary tract (Escherichia coli, Ascaris
worms, or liver flukes) can lead to increased release of
β-glucuronidases that hydrolyze bilirubin glucuronides,
favoring pigment stone formation. Renal failure with
phosphate retention can be a cause of secondary hyperparathyroidism
with hypercalcemia, which increases the
risk of gallstone formation; these stones are mixed stones.
Viral hepatitis is not a risk factor for stone formation. Fatty
foods may trigger the biliary colic, but diet does not play
a direct role in stone formation. Severe ileal dysfunction,
as occurs in Crohn disease, also can predispose to pigment
stones.

Question 63

61 A 78-year-old man has had abdominal pain for a week.
On physical examination he has a temperature of 37° C with
pulse 106/min and blood pressure 85/50 mm Hg. There is left
lower quadrant and right upper quadrant pain. Abdominal
CT imaging shows sigmoid diverticula along with gallbladder
dilation and biliary sludge. A blood culture grows polymicrobial
flora. Which of the following is most likely to cause his
gallbladder disease?
A Hemolysis
B Carcinoma
C Drug reaction
D Lithiasis
E Sepsis

Answer 63

61 E This patient has acute acalculous cholecystitis. The
tachycardia, hypotension, and sepsis with recent illness suggest
that his fluid intake has been poor, with subsequent dehydration
that concentrates bile and promotes stasis. Sepsis promotes
hypotension that increases ischemia of the gallbladder. However,
an isolated, de novo elevation of bilirubin in a hospitalized
patient should suggest the possibility of sepsis. Adenocarcinoma
of the pancreas may produce biliary tract obstruction, but
the CT in this case did not identify a mass. The CT should also
show any gallstones that are present. Intrahepatic cholestasis is
more likely to be an adverse drug reaction.

Question 64

62 A 55-year-old man has developed abdominal pain and
jaundice over 5 weeks. On physical examination, there is right
upper quadrant pain, but no abdominal distention. Abdominal
CT scan shows a markedly thickened gallbladder wall.
A cholecystectomy is performed, and sectioning shows an
enlarged gallbladder containing a fungating, 4 × 7 cm firm,
lobulated, tan mass. Which of the following risk factors is most
likely associated with this mass?
A Alcohol abuse
B Cholelithiasis
C Clonorchis sinensis infection
D Primary sclerosing cholangitis
E Ulcerative colitis

Answer 64

62 B Almost all gallbladder carcinomas are adenocarcinomas,
and most are found in gallbladders that also contain
gallstones. Although alcohol abuse is associated with liver
disease, it is not a significant antecedent to gallbladder disease.
Infection with the biliary tree fluke Clonorchis sinensis is
a risk factor for biliary tract cancer, not gallbladder cancer.
Similarly, primary sclerosing cholangitis increases the risk of
developing cholangiocarcinoma. Ulcerative colitis is associated
with primary sclerosing cholangitis.