Liver Disease, Cirrhosis & Hepatic neoplasms

Question 1

There are two main types of Liver Abscesses

Answer 1

○ Pyogenic Hepatic Abscess
○ Amebic Hepatic Abscess

Question 2

____ means “involving the formation
of pus.” Amebic abscesses are technically
not “pus”-filled, but rather filled with
necrotic debris

Answer 2

“Pyogenic”

Question 3

T/F Immunocompromise is a significant risk factor for both types of hepatic abcesses

Answer 3

T

Question 4

Pyogenic abcesses epidemiology

Answer 4

most commonly occur in patients at
least 50-60 years of age, but
can occur at any age.
■ Diabetes and Hepatobiliary
disease are risk factors

Question 5

Amebic Hepatic Abscess epidemiology

Answer 5

most common in tropical climates
and in areas with poor sanitation.
■ Most often seen in young
males (7-12 times higher)

Question 6

Pathophysiology of pyogenic abcesses

Answer 6

○ Bacteria invade the liver by:
■ Ascending the bile ducts (Ascending Cholangitis)
OR
■ Spread from the GI tract via the Portal Vein
● Often following peritonitis

Question 7

Most common pathogens causing pyogenic abcesses

Answer 7

E coli, Klebsiella pneumoniae

Question 8

Pathophysiology - Amebic abscesses

Answer 8

Amebic abscesses are caused by Entamoeba histolytica after ingestion of a
cyst in contaminated water or food.
○ Trophozoites reach the liver through the portal system.
○ They replicate in hepatic cells and can
lead to a collection of “anchovy-like”
fluid comprised of necrotic tissue.

Question 9

Hepatic Abscesses S/S & differentiating the two types

Answer 9

○ Pain in the right upper quadrant or epigastric region
○ Jaundice is commonly present as well
○ Hepatomegaly and tenderness over the liver are common but not always present

Pyogenic abscesses
○ Fever is usually present

Amebic abscesses
○ Initially, most patients are asymptomatic,
but then progress to abdominal pain and
fever
○ Often a history of recent/current diarrhea
and may have traveled to an endemic area

Question 10

Diagnosis - Hepatic Abscesses

Answer 10

○ Leukocytosis (about 75%) and elevated ALT and AST common.
○ Ultrasound is the recommended initial diagnostic imaging study
○ CT and MRI can be used in gaining a more detailed view.

Question 11

Specific diagnostic testing for pyogenic abscesses

Answer 11

Blood cultures are positive
in 50-100% of Pyogenic
abscess cases.

Question 12

Specific diagnostic testing for amebic abscesses

Answer 12

○ Serology tests for Entamoeba Histolytica antibodies confirms the diagnosis of amebic abscess. (if neg. and concerned, recheck 1 week!!!)
○ Stool O&P testing reveals ameba in
about 1/4 of these patients

Question 13

Treatment - Pyogenic abscesses

Answer 13

● Metronidazole + Duel Antibiotic combo*
● Antibiotics continue for at least 2-3
weeks.
● Drainage is performed, via percutaneous
or endoscopic ultrasound-guided needle
aspirations. This is used for treatment as
well as determining pathogens

Question 14

Treatment - Amebic abscesses

Answer 14

● Amebic abscesses: Metronidazole
+/- a luminal agent is treatment of
choice

Question 15

Signs of Chronic Liver Disease

Answer 15

● Portal Hypertension
● Caput Medusae
● Esophageal Varices
● Ascites: Increased hydrostatic pressure & Decreased oncotic pressure
● Coagulopathy
● Thrombocytopenia –> splenomegaly
● Hypoalbuminemia
● Hyperbilirubinemia→Jaundice
● Spider Angioma

Question 16

Serum ascites albumin gradient (SAAG) =

Answer 16

serum albumin level - ascitic fluid albumin level
■ Greater than 1.1 g/dL (meaning low albumin in the ascitic fluid) indicates
likely portal hypertension (97%) (transudative process).

Question 17

↑Hydrostatic Pressure:

Answer 17

Fluid is pushed out of the vessels = proteins aren’t expelled

Question 18

↓ Oncotic Pressure:

Answer 18

Lower albumin levels in the blood → water expelled to increase relative serum albumin

Question 19

Hepatic Encephalopathy

Answer 19

Hepatic encephalopathy is a syndrome
sometimes observed in patients with
cirrhosis, characterized by acute
personality changes, intellectual
impairment, neuromuscular changes,
and decreased level of consciousness.

Question 20

Etiology of hepatic encephalopathy

Answer 20

● This is caused by multiple mechanisms, but elevated Ammonia levels are believed to be the most common cause.
○ Ammonia is normally broken down & metabolized by themliver, so elevated levels of the toxin can occur with cirrhosis.
● It is believed that Ammonia alters the permeability of the BBB, allowing
neurotoxins to enter and causing neurologic malfunction.

Question 21

Hepatic Encephalopathy is generally treated with _____

Answer 21

Lactulose, which pulls
Ammonia into the lumen of the intestine and helps to excrete the toxin
through the feces. Lactulose is a laxative and initiates diarrhea

Question 22

____ is a physical exam finding that can
be present in several different forms of
metabolic encephalopathy, including
Hepatic Encephalopathy.

Answer 22

Asterixis
○ Patient should have arms extend
outright, with palms out and fingers to
the ceiling. Will be unable to keep hands
still, with “flapping tremor.”

Question 23

Spontaneous Bacterial Peritonitis

Answer 23

● SBP is a significant complication of liver disease where the ascitic fluid becomes spontaneously infected with a bacterial pathogen.
● Most of the time, the source of the bacteria is not identifiable and the development is unexpected
and spontaneous.
● Most common presentation is acute abdominal pain and fever in a patient with ascites.

Question 24

Spontaneous Bacterial Peritonitis Tx

Answer 24

● Emergent diagnostic paracentesis is required so that a peritoneal fluid analysis and culture can be performed.

Question 25

An _____ in the ascitic fluid is the best predictor of Spontaneous Bacterial Peritonitis

Answer 25

elevated neutrophil count

Question 26

_____ is defined as iron overload

Answer 26

Hemochromatosis

Question 27

Hemochromatosis

Answer 27

● Hereditary Hemochromatosis is caused by a genetic changes that leads to the accumulation of iron in vital organs, and iron toxicity.
● A decreased expression or activity of Hepcidin, the principal iron regulatory releasing hormone, which normally inhibits iron absorption by enterocytes of the
gut
● Ultimately, the disease results in increased iron absorption from the duodenum → Iron overload

Question 28

Hemochromatosis - pathophysiology

Answer 28

○ Hemochromatosis is characterized by increased accumulation of iron, in
the form of Hemosiderin, in the liver, pancreas, heart, adrenal glands,
testicles, pituitary, and kidneys.
○ Cirrhosis often develops as the iron causes liver cell death and fibrosis.

Question 29

S/S hemochromatosis

Answer 29

○ Symptoms often do not develop until around 40 in males, postmenopause in women (50’s).
○ Early symptoms include fatigue and arthralgias.
○ Later symptoms include severe arthropathy, hepatomegaly, hepatic
dysfunction, and skin hyperpigmentation or “Bronze skin”.
○ Once liver failure begins, all the signs and symptoms of cirrhosis are possible, including the complications.

Question 30

Dx of Hemochromatosis

Answer 30

■ Mild to moderately elevated Liver Enzymes
■ Elevated plasma iron: Usually >50% Transferrin saturation
○ Testing for HFE (called Homeostatic Iron Regulator) protein mutation is indicated for any patient with evidence of Iron overload, and will be diagnostic.
○ Liver biopsy to assess for cirrhosis, iron deposition

Question 31

Management of hemochromatosis

Answer 31

○ The ultimate goal of treatment is to remove iron stores before the
overload leads to irreversible organ damage.
○ Frequent phlebotomy is the first-line treatment of Hemochromatosis-related iron overload.
○ Joints often need surgically replaced and liver transplant is often needed for cirrhosis that was not prevented by phlebotomy.

Question 32

Wilson’s Disease

Answer 32

(hepatolenticular degeneration)
● Rare autosomal recessive disorder
● It usually manifests before the age of 35.
● There are over 300 different genetic mutations of the Wilson gene on
Chromosome 13 that can lead to the disease

Question 33

Wilsons disease pathophysiology

Answer 33

○ The genetic mutation causes a defect in
the copper transporter ATP7B.
○ This results in the accumulation of copper
throughout the body, and especially in the
liver, due to the inability to fully clear the
copper from the blood.
○ The disease is characterized by excessive absorption of copper from the small intestine and decreased excretion of copper by the liver

Question 34

Wilson’s Disease - S/S

Answer 34

○ Tends to present as liver disease and/or neuropsychiatric disease in young
adults, most commonly under the age of 35 years.
○ Neurologic manifestations are related to copper deposition in the basal ganglia
and can appear similar to Parkinsonism, often preceded by personality changes
or new behavioral concerns.
● Signs and Symptoms- Kayser-Fleischer Rings

Question 35

What is this called and what is it found with?

Answer 35

Kayser-Fleischer Rings found with wilson’s disease

Question 36

Wilson’s Disease Diagnosis

Answer 36

○ Serum ceruloplasmin levels are low in 90% of Wilson’s patients.
○ Urinary copper excretion is greater than 100 mcg/d in 24 hours.
○ Brain MRI may reveal increased signal in the
basal ganglia or midbrain on certain
sequences.

Question 37

Management of wilson’s disease

Answer 37

○ The mainstay of treatment is lifelong use
of chelating agents (making water soluble)
○ Otherwise, treatment is focused on optimizing liver function and treating the complications that arise if cirrhosis has developed.

Question 38

Liver Cirrhosis

Answer 38

Cirrhosis is the 9th leading causes of death in the US and is the end result of
chronic, repeated, or severe hepatocellular injury

Question 39

Liver Cirrhosis - epidemiology

Answer 39

○ Fatty Liver Disease is becoming more common.
○ Alcohol is one of the strongest risk factors for cirrhosis

Question 40

Liver Cirrhosis - Pathophysiology

Answer 40

○ Chronic inflammation and disease of the liver ultimately leads to hepatocellular death.
○ The hepatocellular injury leads to
intercellular fibrosis and atrophy of
the liver.
○ In some cases, nodular
regeneration occurs, resulting in a
nodular, shrunken liver.

Question 41

Liver Cirrhosis S/S

Answer 41

○ May remain asymptomatic for years,
although most have symptoms from the
causative disease
○ Symptoms can include: Fatigue, weakness,
insomnia, muscle cramps, weight loss,
anorexia, nausea/vomiting, decreased libido.

Question 42

Liver Cirrhosis Diagnosis

Answer 42

○ Lab studies are often minimally abnormal until late in cirrhosis.
○ Previously elevated AST and ALT may normalize or even become low as
Cirrhosis develops
○ Ultrasound, CT, and/or MRI can be used to
evaluate the size of the liver
● A liver biopsy is often performed to confirm various diagnosis.

Question 43

What will a Liver Biopsy show in cirrhosis?

Answer 43

● The histologic appearance in cirrhosis is that of fibrosis and nodules.
○ Findings that identify the underlying cause may not be present.
○ Alternatively, the biopsy could be diagnostic for underlying causes
of cirrhosis, like alcoholic liver disease, NASH, etc.

Question 44

When is liver biopsy unsafe?

Answer 44

○ Because of the high risk of bleeding, liver
biopsy is not safe if the INR is greater than
1.6 or if the platelet count is under 60,000.

Question 45

Management of liver cirrhosis

Answer 45

○ Abstinence from alcohol is a key component of treatment.
○ Otherwise, treatment is generally focused on complications as they
arise, such as treating ascites and hepatic encephalopathy.
○ A low salt diet
○ Liver transplant is curative if your patient qualifies.
■ MELD scoring

Question 46

MELD Score

Answer 46

● MELD = Model for End-Stage Liver Disease
○ A well-developed scoring system used to assess the severity of chronic liver disease.
○ MELD-Na includes Sodium into calculation and is more specific
● This evidence-based scoring system has proven useful for determining
prognosis and prioritizing for receipt of a liver transplant.
● Using a complex logarithmic formula, it uses the patient’s dialysis status,
serum Bilirubin, serum Creatinine, INR and Na to predict survival.

Question 47

Hepatocellular Carcinoma (HCC)

Answer 47

● HCC is a malignant neoplasm that arises
from the parenchymal cells of the liver.
● It is very important to remember that
metastatic tumors to the liver are by far the
most common hepatic neoplasms, but HCC
is the aggressive primary hepatic neoplasm

Question 48

80% of all HCCs are associated with ____

Answer 48

Cirrhosis

Question 49

Hepatocellular Carcinoma epidemiology

Answer 49

○ Because of its link to Chronic Hepatitis C, HCC represents one of the
fastest growing cause of cancer deaths in the US.
○ The incidence of HCC is expected to increase dramatically in the coming
decades secondary to the dramatic increase in NAFLD and NASH.

Question 50

Hepatocellular Carcinoma - pathyphysiology

Answer 50

○ The exact pathophysiology or pathogenicity of HCC has not been
definitively determined.
■ It is clearly a multifactorial event and occurs after extensive
hepatic damage and disease.

Question 51

S/S Hepatocellular carcinoma

Answer 51

○ Symptoms from the HCC generally develop later when the patient
suddenly begins to deteriorate clinically.
■ Example: Cachexia, weakness, and sudden weight loss in a cirrhotic
patient that was previously stable.
○ Any time a cirrhotic patient (remember-usually a small, atrophic liver)
develops an enlarging, potentially tender liver, it is HCC until proven
otherwise.
■ Rapidly expanding abdominal mass is possible

Question 52

Dx of hepatocellular carcinoma

Answer 52

○ Sudden and sustained elevation in serum Alkaline Phosphatase in a
patient that was previously stable is a common lab finding.
○ Alpha-Fetoprotein levels are elevated in
70% of HCC. (AFP is not liver specific)
○ CT and MRI are the preferred
imaging studies- reveal a mass.
○ Liver Biopsy is diagnostic, although
seeding by needle is a concern.

Question 53

Hepatocellular Carcinoma management

Answer 53

○ Overall, transplantation remains the best
option for patients with HCC.
○ 1-year survival rate is 23% and 5-year survival rate is 5%