Subiect 5

Liver cirrhosis. Definition. Classification, etiology, pathogenesis, diagnosis,

clinical feature, treatment, prevention, prognosis. Treatment of liver cirrhosis.

1. A 58-year-old male with new onset of jaundice has been addressed to the doctor for evaluation.
He is experiencing no pain and minimal symptoms. His skin has a yellowish hue and his sclera are
icteric. You plan to order labs and perform additional testing to determine the etiology.
Match the following labs with the disease that it can assist with diagnosis:
1. Antismooth muscle antibodies a. Hemochromatosis
2. Ferritin b. Hemolytic anemia
3. Ceruloplasmin c. Autoimmune hepatitis
4. Antimitochondrial antibodies d. Wilson disease
5. Haptoglobin e. Primary biliary cirrhosis

Nr 1
1. Correct Answer: C. Antismooth muscle antibodies can be found in type 1 and type 2
autoimmune hepatitis. Antinuclear antibodies (ANAs) are usually also elevated in autoimmune
hepatitis.
2. Correct Answer: A. Ferritin is used to help in the diagnosis of hemochromatosis. Elevated
ferritin, decreased transferrin, and increased transferrin
saturation are indicative of hemochromatosis, which is a iron storage disease affecting many
organs including the liver.
3. Correct Answer: D. Decreased ceruloplasmin is found in 90% of Wilson disease patients;
however, 20% of carriers also have reduced rates of serum ceruloplasmin. Kayser–Fleischer rings
are present in 99% of patients with the neurologic form of the disease; however, only 30% to 50%
of patients present with the purely hepatic or presymptomatic states of Wilson disease. Definitive
diagnosis of the disease is made by liver biopsy and with quantitative copper assays.
4. Correct Answer: E. Antimitochondrial antibodies are used to screen for primary biliary
cirrhosis.
5. Correct Answer: B. Haptoglobin is a glycoprotein synthesized in the liver that binds free
hemoglobin. It is increased in obstructive liver disease or diseases associated with increased
erythrocyte sedimentation rate (ESR). It is decreased in any type of hemolysis, liver disease,
anemia, mildly with oral contraceptives, or in childhood and infancy.

2. You are asked to consult on a 62-year-old white female with pruritus for 4 months. She has
noted progressive fatigue and weight loss. She has intermittent nausea but no vomiting and denies
changes in her bowel habits. There is no history of prior alcohol use, blood transfusions, or illicit
drug use. The patient is widowed and had two heterosexual partners in her lifetime. Her past
medical history is not significant. Her family history is unremarkable. On examination she is
mildly icteric. She has spider angiomata on her torso. You palpate a nodular liver edge 2 cm below
the right costal margin. The remainder of the examination is unremarkable. A right upper quadrant
ultrasound confirms your suspicion of cirrhosis. You order a complete blood count and a
comprehensive metabolic panel.

Argument your suggestions for possible diagnose.

What is the most appropriate test for diagnose?
A. 24-hour urine copper
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B. Antimitochondrial antibodies (AMA)
C. Endoscopic retrograde cholangiopancreatography (ERCP)
D. Hepatitis B serologies
E. Serum ferritin

Nr 2. The answer is B. The presence of cirrhosis in an elderly woman with no prior risk factors
for viral or alcoholic cirrhosis should raise the possibility of primary biliary cirrhosis (PBC). The
cause is unknown, but autoimmunity is assumed, as there is an association with other autoimmune
disorders, such as autoimmune thyroiditis, CREST syndrome, and the sicca syndrome. The vast
majority of patients with symptomatic disease are women. The antimitochondrial antibody test
(AMA) is positive in over 90% of patients with PBC and only rarely is positive in other conditions.
This makes it the most useful initial test in the diagnosis of PBC. The 24-hour urine copper
collection is useful in the diagnosis of Wilson’s disease. Hepatic failure from Wilson’s disease
typically occurs before age 50.
Hemochromatosis may result in cirrhosis. It is associated with lethargy, fatigue, loss of libido,
discoloration of the skin, arthralgias, diabetes, and cardiomyopathy. Ferritin levels are usually
increased, and the most suggestive laboratory abnormality is an elevated transferrin saturation
percentage. Although hemochromatosis is a possible diagnosis in this case, PBC is more likely in
light of the clinical scenario. Although chronic hepatitis B and hepatitis C are certainly in the
differential diagnosis and must be ruled out, they are unlikely because of the patient’s history and
lack of risk factors.

3. You are evaluating a woman, 52-year-old, who presents complaining of fatigue and itching. She
has been tired for the past 6 months and has recently developed diffuse itching. It is worse in the
evening hours, but it is intermittent. She does not note it to be worse following hot baths or
showers. Her past medical history is significant only for hypothyroidism for which she takes
levothyroxine 125 μg daily. On physical examination, she has mild jaundice and scleral icterus.
The liver is enlarged to 15 cm on palpation and is palpable 5 cm below the right costal margin.
Xanthomas are seen on both elbows. Hyperpigmentation is noticeable on the trunk and arms where
the patient has excoriations. Laboratory studies demonstrate the following: WBC 8900/μL,
hemoglobin 13.3 g/dL, hematocrit 41.6%, and platelets 160,000/μL. The
creatinine is 1.2 mg/dL. The AST is 52 U/L, ALT is 62 U/L, alkaline phosphatase is 216 U/L, total
bilirubin is 3.2 mg/dL, and direct bilirubin is 2.9 mg/dL. The total protein is 8.2 g/dL, and albumin
is 3.9 U/L. The thyroid-stimulating hormone is 4.5 U/mL. Antimitochondrial antibodies are
positive. PANCA and C-ANCA are negative.
What is the most likely cause of the patient’s symptoms?
A. Lymphoma
B. Chronic hepatitis C
C. Primary biliary cirrhosis
D. Primary sclerosis cholangitis
E. Uncontrolled hypothyroidism
Formulate and argue the diagnosis.
Indicate the treatment for this patient

Nr 3. The answer is C. The clinical presentation is consistent with a cholestatic picture, which
can present with painless jaundice and pruritus. There is no other prominent association such as
following hot baths or showers, which occurs in polycythemia vera. Other causes of pruritus
outside of cholestasis include lymphoma and uncontrolled hypo-or hyperthyroidism. However, the
laboratory studies in this patient clearly represent cholestasis with an elevation in alkaline
phosphatase and bilirubin. The clinical characteristics are more commonly seen in primary biliary
cirrhosis compared to primary sclerosis cholangitis, as the patient is a middle-aged female with
positive antimitochondrial antibodies. In contrast, primary sclerosing cholangitis is associated with
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positive perinuclear antineutrophil cytoplasmic antibodies in 65% of patients, and 50% of
individuals with primary sclerosing cholangitis have a history of ulcerative colitis.

4. A 63-year-old man presents to the emergency department complaining of hematemesis. The

vomiting began abruptly and was not preceded by any abdominal pain or other symptoms. He
describes the vomiting as about 500 mL of bright red blood. He has not had melena or bright red
blood per rectum. He has known alcoholic cirrhosis and continues to drink at least 12 beers daily.
He does not seek regular medical care, and he has not previously had an endoscopy to screen for
varices. When he is initially evaluated in the emergency department, he is noted to be tachycardic
with a heart rate of 125 beats/min and a blood pressure of 76/40. After 1 L of IV saline, his blood
pressure increases to 92/56. He has an additional 300 mL of hematemesis upon arriving in the
emergency department. The initial hematocrit is 32%.
Select all the following procedures what should be a part of the initial management of this
patient and argue them
A. Administration of octreotide 100 μg/h by continuous IV infusion
B. Administration of propranolol 10 mg four times daily
C. Emergent GI consult for upper endoscopy
D. Ongoing volume resuscitation with saline and packed red blood cells as needed to maintain
adequate blood pressure
E. Placement of large-bore IV access in the antecubital fossae or large central vein

What is recommended treatment (endoscopic and medication) in variceal bleeding?

Nr 4. The answer A,C,D,E.

In recent years, patients with cirrhosis have been commonly screened for varices by endoscopy,
as about 33% will have varices on examination. Moreover, it is estimated that one-third of
individuals with varices will develop bleeding. The first step in the treatment of any individual
with acute gastrointestinal bleeding is to ensure appropriate large-bore IV access, preferably in a
large central vein or the antecubital fossae, and begin volume resuscitation. Volume resuscitation
should be initiated with normal saline, and blood products should be administered when available.
Once volume resuscitation has been initiated, emergent consultation with GI for endoscopic
evaluation should be obtained.
Endoscopic treatment should include esophageal band ligation, but in the acute setting,
sclerotherapy may be used to control local bleeding with band ligation occurring at a future point
in time. If emergent endoscopy is not an option, placement of a Sengstaken-Blakemore or
Minnesota tube to tamponade bleeding should be employed. In addition, vasoconstricting agents
are used to decrease splanchnic blood flow. The currently preferred agents are octreotide or
somatostatin by continuous infusion. Nonspecific beta blockers such as propranolol or nadolol are
used for the primary or secondary prevention of variceal bleeding, but are not prescribed in the
acute setting as these agents could worsen hypotension.

5. A 58-year-old man with long-standing cirrhosis resulting from hepatitis C develops vague right
upper quadrant pain and weight loss. A right upper quadrant mass is palpable. Serum alkaline
phosphatase is elevated.
Match the most likely disease process.
a. Primary biliary cirrhosis
b. Sclerosing cholangitis
c. Hepatocellular carcinoma
d. Hepatitis D
e. Hemochromatosis
How you will confirm the diagnosis?

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Nr 5. The answer is c.
Hepatocellular carcinoma is more common in men than women and has a peak incidence between
40 and 60 years of age. A major risk factor is cirrhosis. Hepatitis B and hepatitis C are independent
risk factors. The typical patient has preexisting cirrhosis and presents with right upper quadrant
pain and a palpable mass. Serum alkaline phosphatase and alpha-fetoprotein are elevated.
Diagnosis is confirmed by biopsy.
Primary sclerosing cholangitis leads to beaded narrowing of the extra-hepatic (and often
intrahepatic) bile ducts; it usually presents with painless jaundice. Hepatitis D causes acute
hepatitis (with transaminase elevation) in patients with chronic hepatitis B. Hemochromatosis
causes hepatomegaly and mild transaminase elevation; if treatment is not started before cirrhosis
occurs, it can lead to hepatocellular carcinoma.

6. A 58-year-old man with cirrhosis and ascites caused by chronic hepatitis C is hospitalized
because of subtle personality change that develops into frank mental status changes with
confusion. The patient’s wife reports that his stools have been darker than usual and that he has
been unsteady upon arising the last few days. She also reports that he has been reluctant to take
several of his medications recently as he has been reading about natural remedies. On physical
examination, the patient is lethargic, disoriented, and uncooperative. He is afebrile, has clear lungs,
normal heart, distended abdomen with shifting dullness, and no meningeal or focal neurologic
findings. There is mild hyperreflexia and a nonrhythmic flapping tremor of the wrists. Stool is
heme positive. CT scan of the head is normal.
What complication of cirrhosis have been this patient developed?
What are the precipitating factors for this complication?
What is the best initial therapy to address this patient’s mental status changes?
a. Rifaximin 200 mg orally 3 times daily
b. Lorazepam 1 mg orally tid
c. Haloperidol 2 mg intramuscularly q 4 hours prn agitation
d. Omeprazole 20 mg orally tid
e. Lactulose 30 cc orally, titrated to three to four stools daily

Nr 6. The answers are a, e.

This patient has hepatic encephalopathy. Precipitating factors include azotemia, acute liver
decompensation, use of sedatives or opioids, GI hemorrhage, hypokalemia, constipation, infection,
a high-protein diet, and recent placement of a portosystemic shunt (TIPS). The most effective
medical treatment is lactulose, a nonabsorbable disaccharide. Antibiotics such as neomycin,
metronidazole, and rifaximin can also reduce symptoms. The other listed medications have not
been shown to be effective in treating patients with hepatic encephalopathy. Quetiapine is used for
psychosis and depression, lorazepam is useful in alcohol withdrawal and anxiety, haloperidol in
psychosis, and omeprazole in peptic ulcer disease.

7. A 60-year-old man with known hepatitis C and a previous liver biopsy showing cirrhosis
requests evaluation for possible liver transplantation. He has never received treatment for hepatitis
C. Though previously a heavy user of alcohol, he has been abstinent for over 2 years. He has had
two episodes of bleeding esophageal varices. He was hospitalized 6 months ago with acute hepatic
encephalopathy. He has a 1-year history of ascites that has required repeated paracentesis despite
treatment with diuretics. Medications are spironolactone 200 mg daily and lactulose 30 cc three
times daily. On examination he appears thin, with obvious scleral icterus, spider angiomas, palmar
erythema, gynecomastia, a large amount of ascitic fluid, and small testicles. There is no asterixis.
Recent laboratory testing revealed the following:
Hemoglobin = 12.0 mg/dL (normal 13.5-15.0)
MCV = 103 fL (normal 80-100)
Creatinine = 2.0 mg/dL (normal 0.7-1.2)
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 Bilirubin = 6.5 mg/dL (normal 0.1-1.2)
AST = 45 U/L (normal < 40)
ALT = 25 U/L (normal < 40)
INR = 3.0 (normal 0.8-1.2)
What is the best next step in the management of this patient’s liver failure?
a. Repeat liver biopsy.
b. Start treatment with interferon and ribavirin.
c. Refer the patient for hospice care.
d. Continue to optimize medical treatment for his ascites and hepatic encephalopathy and tell the
patient he is not eligible for liver transplantation because of his previous history of alcohol abuse.
e. Refer the patient to a liver transplantation center.

Nr 7. The answer is e. Cirrhosis caused by hepatitis C is the most common cause for liver
transplantation in the United States. A previous history of alcoholism is not a contraindication to
transplantation, although most transplant centers require abstinence from alcohol for 6 months
before transplantation is considered. Three-year survival rate after transplantation in most centers
now exceeds 80%. The model for end-stage liver disease (MELD) scoring system is used in the
United States to allocate cadaveric livers to potential donors. Patients with complications of
cirrhosis (esophageal variceal bleeding, hepatic encephalopathy, and uncontrolled ascites) or who
have significantly elevated bilirubin, INR, and serum creatinine are usually made eligible for
transplantation. Repeat liver biopsy would be unnecessary and potentially risky due to the patient’s
coagulopathy. Patients with end-stage cirrhosis from hepatitis C do not benefit from interferon and
ribavirin therapy. Hospice care is inappropriate until the patient is evaluated by a transplant center.

1. C.M. Decompensated liver cirrhosis with portal hypertension, is characterized by:

a) ascites,
b) “medusa head” on the anterior abdominal wall,
c) astheno-neurotic syndrome,
d) encephalopathy,
e) hidrothorax,
Correct answer: A,B,E
Lecture, Liver cirrhosis. Berliba E.

2. C.M. Decompensated liver cirrhosis with metabolic disorders, is characterized by:

a) jaundice,
b) portal gastropathy,
c) splenomegaly,
d) endocrine/articulare symptoms, muscle pain,
e) skin hemorrhagic manifestations
Correct answer: A,D,E
Lecture, Liver cirrhosis. Berliba E.

3. C.M. Select the drugs used in treatment of autoimmune liver cirrhosis:

a) corticosteroid prednisone,
b) azathioprine,
c) PegInterferon,
d) calcium and vitamine D
e) antibiotics
Correct answer: A,B,D
Lecture, Liver cirrhosis. Berliba E.
4. C.M. Select the drugs used in treatment of primary biliary cirrhosis:
a) Ursodeoxycholic acid
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b) cholestyramine
c) PegInterferon,
d) calcium and vitamine D
e) naloxone
Correct answer: A,B,D,E
Lecture, Liver cirrhosis. Berliba E.
5. C.M. Treatment of portal hypertension in
liver cirrhosis includes:
a) Nonselective beta-blockers
b) Ursodeoxycholic acid
c) Endoscopic variceal ligation
d) Prednisone
e) Transjugular intrahepatic portosystemic
shunting
Correct answer: A,C,E
Lecture, Liver cirrhosis. Berliba E.
6. C.M. Select the ultrasound characteristics of
liver cirrhosis:
a) Dilated portal vein
b) Splenomegaly
c) Dilated bile canaliculi
d) Micronodular appearance
e) Macrovesicular steatosis
Correct answer: A,B,D
HARRISON’S Gastroenterology and
Hepatology. Derived from Harrison’s
Principles of Internal Medicine, 17th Edition
Ed.Dan L. Longo , 2010, p 427. Lecture,
Liver cirrhosis. Berliba E.
7. Which are manifestations of hepatocellular
failure in patients with liver cirrhosis:
a) jaundice
b) coagulation disorders
c) dilated portal vein
d) hypoalbuminemia
e) portosystemic encephalopathy.
Correct answer: A,B,D,E
HARRISON’S Gastroenterology and
Hepatology. Derived from Harrison’s
Principles of Internal Medicine, 17th Edition
Ed.Dan L. Longo , 2010, p 419. Lecture,
Liver cirrhosis. Berliba E.
8. S.C. About spontaneous bacterial
peritonitis, the following statement is
false:
a) It has a risk of hepatorenal syndrome
b) Carry albumin infusion on days one
and three
c) It has a mortality of 10% in the short
and medium term
d) The diagnosis is based on neutrophil
counts in the liquid
e) Cefotaxime is the first choice of
treatment
Correct answer: C
Berliba E. Cours Liver cirrhosis
9. S.C. What type of autoantibody is
characteristic for patients with primary
biliary cirrhosis?
a) Anti liver-kidney microsomes
antibodies
b) Antimitochondrial antibodies
c) Antinuclear antibodies
d) Anti-smooth-muscle antibodies
e) Soluble liver antigen
Correct answer: B
HARRISON’S Gastroenterology and
Hepatology. Derived from Harrison’s
Principles of Internal Medicine, 17th Edition
Ed.Dan L. Longo , 2010, p 423
10. S.C. Which of the following clinical
signs of cirrhosis is due to portal
hypertension?
a) Spider angiomata
b) Clubbing
c) Jaundice
d) Palmar erythema
e) Ascites
Correct answer: E
HARRISON’S Gastroenterology and
Hepatology. Derived from Harrison’s
Principles of Internal Medicine, 17th Edition
Ed.Dan L. Longo, 2010, p 419
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