This patient has 

acute viral hepatitis, which was most likely caused by the hepatitis A virus (HAV).
Anti-HAV IgM are the first immunoglobulins produced in an immune response against HAV and
are used as a confirmatory test for hepatitis A. HAV is transmitted via the fecal-oral route,
usually by ingestion of undercooked contaminated food (esp. raw shellfish) and is endemic in
many tropical and subtropical regions. This patient works as a flight attendant traveling to
foreign countries where hepatitis A might be endemic, which puts her at risk for exposure.

The combination of symptoms of the  stomach  flu  (prodromal  phase),  scleral icterus, dark  urine, and
pale stools with  fever, hyperbilirubinemia, and raised  transaminases  make acute  hepatitis  the most
likely diagnosis.

The tarry bowel movements, use of  naproxen, and mild  hypotension  are suggestive of an  upper GI
bleed, likely arising as a complication of  peptic ulcer disease.

A barium swallow test may be indicated in the case of painful and/or difficulty swallowing.
However, if water-insoluble barium, enters the mediastinum through a perforation
(e.g., Boerhaave syndrome), it may lead to mediastinitis and subsequent fibrosis, making it
contraindicated in this case.

A chest x-ray (CXR) can visualize signs of Boerhaave syndrome and support the clinical

suspicion. Possible findings include a widened mediastinum, pleural effusion,
and pneumothorax. While it is the first initial test of choice in all patients with chest pain and
suspected Boerhaave syndrome, it cannot confirm the diagnosis of Boerhaave syndrome, as a
different method is able to identify the exact location and size of the esophageal rupture.

CT scan of the chest is the test of choice for confirming Boerhaave syndrome in this patient
since he is hemodynamically unstable (low systolic pressure, high pulse). Other indications
include uncooperative patients or cases of inconclusive x-rays and contrast esophagrams. CT
findings include widened mediastinum, esophageal wall thickening,
and/or pneumomediastinum, and it locates the tear in the esophagus wall. The CT scan is also
capable of detecting potential pneumothorax, pneumoperitoneum, subcutaneous emphysema,
and/or pleural effusion. If the patient is stable and there are no signs
of pneumoperitoneum, contrast esophagram with gastrografin (not barium!) is the appropriate
test for confirming the suspected diagnosis.

This patient has worsening  right lower quadrant  tenderness together with  low-grade  fever  and an
elevated  WBC. Based on these features, one possible diagnosis is  appendicitis.
PCR for hepatitis C virus RNA is the confirmatory test for a chronic hepatitis C infection.
The hepatitis C antibody test is a screening test and is positive in cases of active, chronic, or
previous infection. The woman in the case last used IV illicit drugs 5 years ago and has been
symptomatic for 3 months with clinical features of cirrhosis and portal hypertension, which
suggests a chronic hepatitis C infection. The cutaneous erosions and blistering on the dorsum of
this patient's hands are likely due to porphyria cutanea tarda, a common extrahepatic
manifestation of chronic hepatitis C.

This patient has classical findings of  Clostridioides difficile  infection following  antibiotic  use, including
watery,  foul-smelling  stools occasionally streaked with blood,  leucocytosis, as well as mild diffuse
tenderness throughout the lower abdominal quadrants, indicating an
inflamed  colon  (i.e.,  pseudomembranous colitis).

Enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) antigen is one of the screening

tests for Clostridioides difficile (C. difficile) infection, the most likely diagnosis in this
patient. EIA for C. difficile toxins A and B is another screening test often performed in
conjunction with GDH testing. C. difficile infection may also be diagnosed via PCR testing of
stool for C. difficile genes, or by bacterial culture.

Fecal lactoferrin could be ordered if inflammatory bowel disease (IBD) were being

considered. IBD often presents with diarrhea, which is more often bloody if ulcerative colitis is
the diagnosis. IBD usually has a chronic course and various extraintestinal symptoms
(e.g., uveitis, erythema nodosum, pyoderma gangrenosum) may occur.

Dilation of the colon with loss of haustration is a typical finding of toxic megacolon, the

diagnosis in this patient. The dilation smooths out the physiological pouches in the colon wall,
resulting in a loss of its segmented appearance. Abdominal x-ray is the best initial diagnostic
test to diagnose this condition.

This patient has a history of recent  ciprofloxacin  treatment and watery  diarrhea, which should raise
suspicion of  pseudomembranous colitis. She now presents with severe abdominal  pain, nausea,
vomiting,  leukocytosis, and signs of  sepsis, indicating  toxic megacolon, which is a potential
complication of  pseudomembranous colitis.
A dilated sigmoid colon resembling a coffee bean, also known as the coffee-bean sign, is seen in
sigmoid volvulus, which appears mostly in elderly adults and presents with constipation,
abdominal pain, nausea, and vomiting

Oral fidaxomicin is a first-line therapy used to treat initial episodes of Clostridioides

difficile infection. This condition typically manifests with abdominal symptoms and
severe diarrhea following antibiotic therapy (e.g., clindamycin in this case), which disrupts the
normal gastrointestinal flora. In addition to discontinuing the inciting antibiotic, management
includes correction of fluid losses and electrolyte imbalances. Oral vancomycin is another
appropriate first-line therapy for initial episodes of Clostridioides difficile infection.

A hydrogen breath test is used to diagnose lactose intolerance. In patients with lactose

intolerance, breath hydrogen levels are increased (> 20 ppm) following the ingestion of
a lactose-loaded drink because bacterial fermentation of undigested lactose in the large
intestine releases hydrogen, which is then reabsorbed into the blood from the large
intestine and eliminated by the lungs. Since lactose-loading can cause
severe diarrhea and dehydration in young children, or they may refuse to actively participate in
a hydrogen breath test, a stool acidity test is preferred in this age group (lactose
intolerance causes increased stool acidity).

Diagnosis is based on the Rome IV criteria for irritable bowel syndrome, which include recurrent
abdominal pain at least 1 day per week during the previous 3 months that is associated with a
change in stool frequency and stool form in the absence of any red flag symptoms such as
nighttime pain, blood in the stool, weight loss, or fever, which would indicate organic disease.

Anti-Saccharomyces cerevisiae antibodies are associated with Crohn disease, which typically

manifests with chronic diarrhea (> 4 weeks) and signs of malabsorption, as in this patient.
However, the negative fecal lactoferrin test makes this diagnosis unlikely.

Endoscopic retrograde cholangiopancreatography is used to

diagnose choledocholithiasis and cholangitis.
Epinephrine is the treatment of choice for anaphylaxis. The patient underwent a CT-
guided PAIR (puncture, aspiration, injection, and reaspiration) procedure, during which he
developed hypotension, tachycardia, decreased oxygen saturation, and
severe bronchospasm (as evident by a sudden decrease in end tidal CO  and absent breath
2

sounds). These features suggest anaphylaxis, which is probably the result of leakage of highly
antigenic cystic fluid into blood or the peritoneal cavity.

Based on his  right upper quadrant  pain, nausea, vomiting, close contact with a dog,  eosinophilia, and
focal cyst within the  liver, the diagnosis in this patient is most likely  hydatid cyst disease. The contents
of a  hydatid cyst  are highly antigenic.

The combination of  dysphagia  to solids and liquids, the bird-beak appearance on  esophagram, and the
manometry findings (impaired relaxation of the  lower esophageal sphincter) is indicative of  achalasia.

Gastroesophageal endoscopy is indicated in this patient to rule out a malignancy (e.g., cancer of

the esophagus or the gastroesophageal junction) as a cause of signs of achalasia (referred to
as pseudoachalasia). Distal esophageal cancer and achalasia can present similarly, which is why it
is important to maintain a high index of suspicion for esophageal cancer.
Additionally, achalasia itself predisposes to esophageal cancer, although cancer is unlikely to
arise within a period of just 6 months. But in this particular patient, significant weight loss and a
history of smoking are findings that would support the diagnosis of esophageal cancer, making
endoscopic inspection necessary.

A female with fatigue, generalized itching, elevated  cholestatic parameters  (bilirubin  and  alkaline
phosphatase), and normal or slightly elevated  aminotransferases  suggests a diagnosis of  primary
biliary cholangitis  (PBC), an autoimmune  liver  disease that occurs mostly among women.
Positive  ANA  and  AMA  confirm the diagnosis.

Ursodeoxycholic acid is a bile acid used as the first-line therapy for PBC, slowing down disease
progression and providing relief for symptoms like itching. Although the cause
of pruritus in PBC is not fully understood, it is likely independent of bile acid skin deposition,
because even patients with PBC and normal bilirubin values often present with pruritus. An
increase of endogenous opioids could account for this symptom.
This young white man has fatigue,  chronic diarrhea, abdominal  pain, and  thrombocytosis, which
suggests  inflammatory bowel disease  (IBD). Although the two principal types of  IBD  (Crohn's
disease  and  ulcerative colitis) have similar features, the presence of
bloody  diarrhea  indicates  ulcerative colitis  as the most likely cause of his symptoms.  Crohn's
disease  rarely presents with bloody  diarrhea, and is more often associated with weight loss
and  malnourishment, which this patient does not have.

Colonoscopy is used for the screening of colorectal cancer and is also the recommended test for
diagnosing inflammatory bowel disease, including ulcerative colitis. Typical findings
of colonoscopy in patients with ulcerative colitis include inflamed, reddened mucosa, bleeding
on contact with the endoscope, and fibrin-covered ulcers.

In contrast to other autoimmune hepatobiliary diseases, primary sclerosing cholangitis (PSC) is

more frequent in men. Although in earlier stages it is usually asymptomatic, patients in the later
stages present with pruritus, jaundice, elevated parameters of cholestasis, and wall thickening
and irregular diameter of the bile duct on ultrasound. PSC is classically associated with ulcerative
colitis. (See table “Differential diagnoses of primary cholangitis”)

This  22-year-old  woman with chronic abdominal  pain, bloody  diarrhea,  significant weight
loss,  proctitis  (as evident by  pain  on defecation with an unremarkable rectal exam), and a positive  p-
ANCA  test probably has  ulcerative colitis.

p-ANCA: perinuclear antineutrophil cytoplasmic antibodies

Topical nystatin is the first-line treatment for patients with oral thrush, which typically gives way
to red, inflamed, or bleeding areas when scraped off. Further common findings
include pain while eating, loss of taste, and a cottony feeling in the mouth. This patient has
several risk factors for oral candidiasis such as immunosuppression due to chemotherapy and a
hematologic malignancy (i.e., non-Hodgkin lymphoma). Other topical antifungals used for the
treatment of oral thrush include clotrimazole and ketoconazole.

The secretin stimulation test (SST) is a confirmatory test for gastrinoma, which is the

most likely diagnosis based on this patient's clinical presentation and her endoscopy
findings (peptic ulcer disease resistant to medical therapy). However, SST is not the best
initial test for diagnosing gastrinoma, as it is less sensitive than other screening
modalities.
Determining the fasting serum gastrin level is the best initial test for
diagnosing gastrinoma (Zollinger-Ellison syndrome). A 10-fold increase in gastrin levels is
conclusive evidence of a gastrinoma. A gastrin-producing tumor is suggested by the patient's
extended course of symptoms and multiple peptic ulcers that have been refractory to proton
pump inhibitor therapy. Even though gastrinomas are a rare cause of peptic ulcer disease (PUD),
more than 95% of patients with gastrinoma present with PUD. More frequent causes of PUD,
such as infection with Helicobacter pylori or long-term use of NSAIDs can be ruled out based on
patient history.

Octreotide causes splanchnic vasoconstriction, which decreases portal venous pressure by

reducing the amount of blood in the portal veins. However, the effect of octreotide is only
transient because rapid drug tolerance develops, probably due to downregulation
of somatostatin receptors. While octreotide is effective in the treatment of acute variceal
hemorrhage, it should, for this reason, not be used for secondary prophylaxis.

Endoscopic variceal ligation (EVL) should be performed every 1–2 weeks until the varices have
been obliterated, after which endoscopic examination should be performed every 3–6 months.

Giardiasis is the most common parasitic cause of diarrhea in the US. It is caused by Giardia
lamblia, which can be acquired from drinking untreated water (natural springs,
streams). Metronidazole is an antibiotic that is effective against anaerobes and protozoa and is a
commonly used treatment for giardiasis. Side effects include nausea and a metallic taste in the
mouth. Patients should be advised not to consume alcohol while taking metronidazole because
it can lead to a disulfiram-like reaction with nausea and vomiting.

Fever, nausea, vomiting, lethargy, and  jaundice  with extremely high  liver  enzyme levels is diagnostic
of  acute viral hepatitis. Features of  hepatic encephalopathy  (drowsiness,  asterixis) and
increased  prothrombin time  indicate  fulminant hepatic failure. A particular hepatotropic virus is
associated with an increased risk of  fulminant hepatitis  during  pregnancy.

Hepatitis E infection during pregnancy is associated with a high mortality rate (as high as 10–

25% during the third trimester) due to fulminant hepatic failure. The exact mechanism behind
this phenomenon is not known. Anti-HEV antibodies begin to rise (IgM first and IgG after a few
days) 2 weeks after hepatitis E infection (or 1 week before the onset of symptoms). However, IgG
antibodies can persist for life. Therefore, IgM antibodies, which would return to baseline within
4–6 months, are used to differentiate between acute HEV infection and a past infection. The
history of recent travel to an HEV-endemic country (e.g., Sudan) is a risk factor for hepatitis
E infection and it is transmitted feco-orally.

Fulminant hepatitis is when your liver begins to fail very quickly: within days or weeks,
depending on the cause. This sudden liver failure can happen in people who previously had
stable liver disease or never had liver problems.
Fulminant hepatitis is a rare syndrome of massive necrosis of liver parenchyma and a
decrease in liver size (acute yellow atrophy) that usually occurs after infection with
certain hepatitis viruses, exposure to toxic agents, or drug-induced injury.
Laboratory tests to confirm the diagnosis of fulminant hepatitis include liver tests (eg,
transaminases, bilirubin) and other tests to evaluate liver function (prothrombin time/international
normalized ratio [PT/INR], albumin).

In a patient with an active chronic hepatitis B infection, antiviral therapy with tenofovir, entecavir,

or pegylated interferon-alpha is indicated if ALT levels are more than 2 times the upper limit or
if cirrhosis is present. In this patient, an ALT level of 456 U/L indicates that antiviral therapy is
necessary. IFN-α is, however, contraindicated among patients with autoimmune diseases such
as systemic lupus erythematosus because immune system upregulators such as interferon can
cause an exacerbation of autoimmune disease. The drugs of choice for this patient are therefore
either tenofovir or entecavir. Therapy is aimed at reducing HBV DNA below a detectable level,
achieving seroconversion (negative HBeAg with positive anti-HBe titers), and preventing
progression to end-stage liver disease.

The most important indication for N-acetylcysteine (NAC) is acetaminophen toxicity. Although

this patient's acetaminophen level is within the normal range, NAC is indicated as it improves
transplant-free survival even in patients with non-acetaminophen-related acute liver failure. In
addition, this patient's acute (viral) hepatitis makes her more susceptible to hepatotoxins that
may contribute to liver failure, including acetaminophen. Patients with fulminant liver
failure should be transferred to an intensive care unit at an active liver transplant center, as
worsening encephalopathy and coagulopathy might make a later transfer difficult. In addition
to NAC, subsequent management includes close monitoring as well as treating the underlying
cause (e.g., tenofovir for hepatitis B infection in this patient) and complications such
as coagulopathy and/or encephalopathy. Ultimately, many patients will have to undergo liver
transplantation. However, given this patient's continued IV drug use, she does not qualify
for liver transplantation.