Because of

Report
Problem Based Learning Module
February 25, 2013
Chief Complaint: “My abdomen is bloated”
RF is a 55-year-old African American woman referred to the
hepatology clinic by her primary care physician because of an increase
in abdominal girth over the past month in association with abnormal
liver tests.
RF reports progressive increase in abdominal girth, and leg swelling
for the past month, associated with symptoms of abdominal
discomfort, early satiety and nausea, without vomiting. She has had
no change in bowel habits. She has no fever, chills or weight loss. She
has no prior known history of liver disease and no family history of
liver disease. She drinks 2-3 glasses of wine daily with dinner but she
has not had any since she developed her symptoms. She has no
history of drug use and does not recall having had blood transfusions,
tattoos or body piercing. She noted increased itching in the evening
for the past year; she is taking Benadryl OTC which is controlling her
symptoms.
Past Medical History
• Hypertension dx 5 years ago
• Hysterectomy for vaginal bleeding in 1999
• Splenectomy after a motor vehicle accident at age 6
• Screening colonoscopy at age 53 with no polyps
detected
ROS
• Increased fatigue and difficulty sleeping at night: has
been on medical leave from her work for the past 3
weeks.
• Chronic back pain relieved with ibuprofen
Medications
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Atenolol 50 mg daily
Ibuprofen 400 mg po tid as needed for back pain
Calcium and vitamin D twice a day
Multivitamin once daily
Benadryl 25 mg QHS for itching
Family History
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Mother with hypertension
Father with hypertension, diabetes and CAD
Sister with hypertension and cervical cancer
No liver disease
Social History
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Never smoked
Never used drugs
Drinks wine with dinner regularly (as in HPI)
Works as a teller at a bank. Married, lives with her husband and has 2 adult children.
Physical Exam
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Vital signs: P: 68, BP: 122/76, R: 10, T: 98.9, 98% sat on room air
Wt 220 lbs, Ht 5’7”
General: Evidence of temporal wasting
HEENT: Slightly icteric
Neck: supple without adenopathy or jugular venous distention
Cardiovascular: normal rate, regular rhythm, no murmurs
Chest and lungs: symmetrical expansion, clear to auscultation and
percussion
Abdomen: LUQ scar of prior splenectomy. Distended abdomen, tense,
mild diffuse tenderness to palpation. Dull to percussion at the flanks with
evidence of shifting dullness. No fluid wave detected.
Extremities: without clubbing or cyanosis; 1+ lower extremity edema
appreciated bilaterally.
Neurologic examination: normal exam. Fully alert and oriented. No
asterixis.
Labs
Component
WBC
Hgb
MCV
Platelets
INR
Na
K
BUN
Creatinine
Albumin
Total bilirubin
Alkaline Phosphatase
AST
ALT
Ferritin
Reference range
(4.5-13.5 THO/μL)
(13-16 g/dL)
(83 – 93)
(150-400 THO/μL)
(0.9-1.1)
(134-142)
(3.6 – 5.0)
(10-20)
(0.6-1.35 mg/dL)
(3.6-5.0 g/dL)
(0.3-1.2 mg/dL)
(38-120 U/L)
(10-40 U/L)
(9-60 U/L)
Value
12 THO/μL
10.9 g/dL
96
140 THO/μL
1.7
134
4.0
8
1.0 mg/dL
3.2 g/dL
4.4 mg/dL
187 U/L
128 U/L
78 U/L
12
HAV serologies
Negative
HBV serologies
Negative
HCV antibody
Positive
AFP
ASMA
ANA
Ig Quant
(0-5 IU/mL)
(Less than 1:20)
(Less than 1:40)
8 IU/mL
1:40
1:160
IgG 1.6 g/mL (ULN 1.2)
IgA, IgM within normal
Imaging
Ultrasound of the abdomen was obtained. The
liver had a heterogeneous echotexture, but did
not appear nodular. No focal liver lesions. The
hepatic and portal veins appeared patent by
Doppler. Large amount of ascites noted.
Gallbladder is normal. Spleen is absent. Kidneys
are of normal size and echogenicity, no
hydronephrosis.
Ascites
•Ascites occurs when there is a disruption in the pressure forces
between intravascular and extravascular fluid spaces, which
allows extravascular fluid to accumulate in the anterior
peritoneal cavity
•Ascites in cirrhosis results from sinusoidal HTN and sodium
retention.
•Peripheral arterial vasodilation hypothesis
•Renal sodium (and water retention) is due to reduced effective blood volume 2/2
peripheral arterial vasodilatation.
•The overfill hypothesis
• Renal retention of sodium is primary with secondary vascular changes
and accumulation of ascites and edema.
Sherlock's Diseases of the Liver and Biliary System. Twelfth Edition. Edited by James S. Dooley, Anna S.F. Lok,
Andrew K. Burroughs, E. Jenny HeathCote. 2011.
Pathophysiology of
veins compressed and
Ascites Central
obstructed by fibrosis and
regenerative nodules,
reducing venous outflow
Sinusoidal pressure
elevated
Lymph from subdiaphragmatic and peritoneal
lymphatics removal via thoracic duct to limit of
capacity
Sinusoidal
baroreceptor
s stimulated
Central
vein
Portal vein
engorged pressure
increased
Increased
splanchnic
lymph flow
adds to ascites
Portalsystemic collateral
vessels
Some lymph reabsorbed
by peritoneal and
subdiaphragmatic
lymphatics
If lymph formation >
lymph reabsorption,
excess accumulation
in peritoneal cavity as
ascites
Classification by mechanism of ascites formation
I. Elevated hydrostatic pressure (portal hypertension)
A. Cirrhosis
B. Hepatic congestion:
Congestive heart failure
Constrictive pericarditis
Inferior vena cava syndrome
Hepatic vein obstruction (Budd-Chiari syndrome)
C. Portal vein occlusion
II. Decreased osmotic pressure
A. Hypoalbuminemia:
Nephrotic syndrome
Protein-losing enteropathy
Malnutrition
B. Cirrhosis or hepatic insufficiency
III. Fluid production exceeding resorptive capacity (associated with peritoneal disease)
A. Infections:
B. Bacterial peritonitis (acute; spontaneous forms)
Tuberculosis, Fungal, Parasitic
C. Malignancy:
Metastatic carcinoma
Primary mesothelioma
D. Granulomatous peritonitis
Infections
Cancer
Iatrogenic: starch, barium
Vasculitis
http://depts.washington.edu/physdx/liver/path.html
Discuss the finding of a
distended abdomen on exam in
our patient and the diagnostic
accuracy of physical exam
maneuvers in identifying ascites
as a cause of abdominal
distention.
Ascites: Physical Exam Reliability
•Findings: distension, bulging flanks, flank
dullness, shifting dullness, and fluid wave
•Reliability? Depends on examiner…
• In one study, 3 internists, 90 inpatient veterans
•Presence/absence of abdominal distension (86%),
Bulging flanks (79%), shifting dullness (78%), fluid wave
detection (76%)
•In one study, 6 GI MDs, 50 alcoholics examined
for ascites
• ICC was 0.75 (overall) and 0.95 (senior physicians)
Espinoza P, Ducot B, Pelletier G, et al. Dig Dis Sci. 1987;32:244-247. Cummings S, Papadakis M, et al West J Med.
1985; 142:633-636.
Accuracy of Physical Exam
Maneuvers
• No single sign is specific and sensitive, but flank dullness
(≥0.8) and bulging flanks (≥0.72) are sensitive!
• Absence of a fluid wave is very specific (≥0.82)!
Cummings S, et al. West J Med. 1985; 142:633-636; Simel DL, et al. J Gen Intern Med. 1988;3:423-428;
Cattau EL Jr et al. JAMA. 1982; 247:1164-1166.
Accuracy of Physical Exam
Maneuvers (Pooled Data)
• Useful for ruling in ascites: Presence of fluid wave and
shifting dullness!
• Useful for ruling out ascites: Absence of bulging flanks,
flank dullness, and shifting dullness!
• Accuracy depends on examiner, technique used, clinical
setting (habitus), and amount of fluid present!
Williams JW et al. JAMA. 1992; 267 (19): 2645-2648.
What other physical exam findings would you look for that would
you look for that would help with the differential diagnosis?
Features of Cirrhosis in Physical Exam: Spider angiomata, palmar erythema, caput medusae,
jaundice, icterus, fetor hepaticus, dupuytren’s contracture, hepatomegaly, firm/nodular liver
Elevated JVP: heart failure or constrictive pericarditis as a cause. However, Cirrhosis with
tense ascites or pulm HTN can cause this.
Lymphadenopathy: Sister Mary Joseph nodule with ascites may be caused by gastric or colon
CA, HCC, or lymphoma.
Hypothyroidism: thyroid may be enlarged, skin dry with brittle hair, tongue enlarged, periorbital edema, delayed peripheral deep tendon reflexes
Hemochromatosis: skin grayish or bronze and appears dirty, degenerative arthritis of
extremities (usually hands and fingers, especially affected are PIPs of the middle and ring
fingers)
Wilson’s disease: before age 50 – Eye –Kayser-Fleisher ring: brownish green ring near limbus
edge of iris – represents copper deposition in Descemet’s membrane
Nails: bluish discoloration of the lunula (azure lunule; not specific)
Sleisinger & Fordtran’s Gastointestinal and Liver Disease Pathophysiology/Diagnosis/Management
What is your assessment of the patient’s
alcohol intake?
• Our patient takes in 36 g/alcohol based on 3
drinks/day
• Standard drink in the US: 12 oz of 5% ABV beer, 5 oz of 12%
ABV wine, or 1.5 oz of 80 proof spirit
• Assuming a standard drink has 12 g of alcohol
• Risk of developing cirrhosis is >60-80 g/day of alcohol for >10
years in men and 20 g/day in women. This leads to a 6-41%
chance of developing cirrhosis
www.aasld.org/practice guidelines: Alcoholic Liver disease January 2010
What other elements of history would you like to obtain to
ascertain whether the patient has signs of alcohol dependence?
• The amount and duration of alcohol intake is important
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How long have you been drinking for?
How much do you consider one glass of wine?
How many days per week do you drink?
Do you drink anything else with your wine?
• DSM criteria for Alcohol Dependence
• Tolerance: Have you noticed the need for increased amounts of alcohol to get the
desired effect? or Do you feel the effects of alcohol less despite drinking more?
• Withdrawal: Do you experience symptoms of withdrawal and does alcohol relieve
these symptoms?
• Have you used alcohol for longer or in more amounts then you originally intended?
• Have you tried to cut down but failed?
• Do you find yourself spending a lot of time trying to either get/use alcohol or
recover from its effects?
• Have you shunned other obligations because of alcohol?
• Did you know that cirrhosis can be caused by drinking? If yes, did you keep drinking
knowing this?
Discuss the abnormalities in liver associated enzymes, markers of liver
synthetic function, and CBC on presentation in our patient and how this helps
you in formulating a differential diagnosis for the cause of her symptoms.
Aminotransferases
• AST> ALT but not 2X
• T. bili elevated (presumably direct)
• Alkaline phosphatase elevated
CBC
• Thrombocytopenia
• Normocytic anemia
Synthetic function
• INR elevated
• Albumin low
Discuss the finding of a low Ferritin
level on initial evaluation.
Ferritin
• Levels are difficult to interpret in chronic liver
disease
• Chronic HCV may lead to a  in serum ferritin, but
marked hepatic iron overload is rare
• Hyperferritinemia is also seen in inflammation,
alcohol abuse, liver necrosis, steatosis, DM2,
metabolic syndrome, etc.
• A low ferritin in a patient with chronic liver
disease and anemia is concerning for iron
deficiency anemia
What was the significance of a positive hepatitis C antibody? What
are the sensitivity and specificity of this finding in detecting a
chronic hepatitis C infection?
The serologic tests used to diagnose HCV include three different types of assays that can detect antibodies to
hepatitis C virus: enzyme immunoassay (EIA), chemiluminescent assay (CIA), and recombinant immunoblot assay
(RIBA)
EIA – 3rd generation … detects antibodies against epitopes derived from the HCV core, nonstructural 3,4, and 5
regions.
Recombinant immunoblot assay (RIBA) identifies the specific antigens to which antibodies are reacting in the EIA,
and the results are interpreted as positive (2 or more antigens), indeterminate (1 antigen), or negative (0
antigens)
3rd generation HCV EIA has an estimated 98% sensitivity for detecting antibody to HCV.
Sensitivity is almost 100% in healthy adults with chronic HCV infection
False negative result in pt with acute HCV infection, patients on long term hemodialysis, and immunosuppressed
persons
Good specificity but the predictive value of a positive result varies substantially based on the pre-test probability
of HCV infection. False positive results can occur in some patients who have autoimmune liver disease or
hypergammaglobulinemia
Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for
the Study of Liver Diseases. Diagnosis, management, and treatment of
hepatitis C: an update. Hepatology. 2009;49:13
All positive EIA results should be verified with an independent supplemental test of high specificity (HCV
RNA testing or RIBA). The serologic tests can establish that a person has been infected with HCV at some
point in time, but they do not distinguish active from past (resolved) infection.
http://depts.washington.edu/hepstudy/hepC/clindx/virus/discussion.html
http://depts.washington.edu/hepstudy/hepC/clindx/acute discussion.html
http://depts.washington.edu/hepstudy/hepC/clindx/acute/discussion.html
What are the risk factors for chronic HCV?
Risk Factors:
• Health care worker who has been exposed to infected blood
• Prior injection of illicit drugs, especially with shared needles,
or intranasal cocaine
• History of HIV
• Received a piercing or tattoo in an unclean environment using
unsterile equipment
• Received a blood transfusion or organ transplant before 1992
• Received clotting factor concentrates before 1987
• Have been on HD treatments for a long period of time
• Mother infected with HCV at the time of child’s birth
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009
Who should be screened in the general population?
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009
CDC screening guidelines
MMWR, August 17, 2012; Vol 61;4
What is the likely mode of transmission of HCV to our patient?
•
Injection drug use (currently the most common means of HCV
transmission in the United States)
Denies
Receipt of donated blood, blood products, and organs (blood screening
became available in 1992)
Splenectomy at age 6
•
Needlestick injuries in health care settings
No history of needlestick
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Birth to an HCV-infected mother
No family history
of liver disease
HCV can also be spread infrequently through sex with an HCV-infected
person
Low likelihood
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Sharing personal items contaminated with infectious blood, such as
razors or toothbrushes
Low likelihood
Other health care procedures that involve invasive procedures, such as
injections
Low likelihood
http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#b1
What are the factors associated with
a severe liver injury due to hepatitis
C?
Factors Associated with Severe
Liver Injury due to HCV
• Age
• Race
• Gender
• Co-infection (HIV/HBV)
• Alcohol use
• High BMI
• Hepatic steatosis
• Insulin resistance
• Genetics
• Mode of acquisition?
• Marijuana
• Environment/geography
• Viral factors?
• Amount of
inflammation/fibrosis on
liver biopsy
Chopra S. Clinical Manifestations and natural history of chronic hepatitis C infection. In: Up to Date,
Basow, DS (Ed), Up to Date, Waltham, MA 2012.
Discuss the clinical significance of a positive ANA and elevated
IgG fraction in our patient.
The problem is that ANA is not a specific test. Because it tests for several
different antibodies, cross-reactions can occur.
And up to 45 percent of people with autoimmune thyroid conditions or
rheumatoid arthritis and up to 15 percent of people with HIV or hepatitis C can
have a positive ANA test result.
In addition, up to 3 percent of the normal population can have a false positive
ANA test result.
Hypergammaglobulinemia is frequently observed in patients with
chronic liver disease (CLD) of different causes.
Narciso-Schiavon JL et al. Antinuclear antibody positivity in patients with chronic
hepatitis C: clinically relevant or an epiphenomenon. Eur J Gastroenter Hepatol. 2009
Apri; 21(4) 440-6.
Muryama S. et al. Serum immunoglobulins in patients with chronic hepatitis C: a
surrogate marker of disease severity and treatment outcome. Hepatogastroenterology
2007; 54:493-8.
Are there additional tests that you would like to obtain at the time
of the initial evaluation of our patient?
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HCV RNA
HCV genotype
HIV
Ascites tap for cbc with differential, total protein,
albumin, and culture
• MELD calculation: currently 18
• EGD
• Liver biopsy? We already know she has cirrhosis so
unnecessary
Are there additional management interventions that
you would recommend after initial evaluation?
• Alcohol cessation
• Paracentesis
• Analyze ascites for:
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Cell count + differential
Albumin
Culture
Protein
Diuretics, Na restricted diet
Vitamin K trial
Avoid NSAIDS
Referral to tertiary care for transplant evaluation
Immunize for HAV, HBV, influenza, and pneumovax
Follow Up
Visit A - Initial Intervention
The patient underwent an 8.1 L paracentesis with albumin
replacement. Ascitic fluid analysis revealed an ascitic fluid
protein of 1.0, albumin < 1.0, WBC 35. Ibuprofen was stopped,
she received diet counseling for a 2 gram Na restricted diet.
Spironolactone 100 mg daily and furosemide 40 mg daily were
started.
Visit B- Two months follow up
She presents for follow up 2 months later. She has been
abstinent of alcohol. Ascites is controlled on diuretics. The
following laboratory tests are obtained on follow up.
Pathogenesis of HCV –
Determinants of Persistence
•Inability to clear virus due to host-virus
interplay -> immune response mediating
hepatocyte destruction and fibrosis
•Evasion of immune responses via several viral
mechanisms
•Inadequate induction of innate immune response
•Insufficient induction or maintenance of an
adaptive immune response
•Production of viral quasispecies
•Induction of immunologic tolerance
Feldman M, ed (et al.) Sleisinger and Fordtran’s Gastrointestinal and Liver Disease. Pathophysiology/Diagnosis/Management. 9
th
edition. Philadelphia: Saunders: 2010.
What is the current standard of care
in treatment of hepatitis C infection
and the expected outcome of
treatment in the general population
of infected patients?
Treatment for HCV (Genotype 1)
• Standard of care: PegIFN α, weight based ribavirin, and
PI (telaprevir or boceprevir)
• Telaprevir is effective in treatment-naïve patients,
relapsers, partial responders, and null responders
• Boceprevir is effective in treatment-naïve patients,
relapsers, and partial responders
• Efficacy is influenced by prior treatment status and by
changes in viral load during therapy, which in turn
influences the recommended duration of treatment.
www.aasld.org/practice guidelines: Treatment of Genotype 1 HCV 2011 Practice Guidelines
www.hepatitiscnewdrugs.blogspot.com
www.hepatitiscnewdrugs.blogspot.com
Response Rates with Genotype 1 (on
Triple Therapy)
• Treatment-naïve patients: 67-75%
• Prior relapsers: 69-88%
• Prior partial responders:40-59%
• Prior null responders: 23-38%
• African American: 40-50%
• Cirrhotics (compensated): 14-62%
www.aasld.org/practice guidelines: Treatment of Genotype 1 HCV 2011 Practice Guidelines; Sherman KE et al. Hepatology 2010;
52:401A. Poordad F et al. N Engl J Med. 2011;364(13):1195. Kwo PY et al. Lancet. 2010;376(9742):705. Hezode C et al. N Engl
J Med. 2009;360(18):1839. Akuta N et al. Hepatology. 2010;52(2):421. Jacobson IM et al. N Engl J Med. 2011;364(25):2405.
McHutchinson JG et al. N Engl J Med. 2009;360(18):1827. Bacon BR et al. N Engl J Med. 2011;364(13):1207. McHutchinson JG
et al. N Engl J Med. 2011;364(13):1207. Zeuzem S et al. N Engl J Med. 2011;364(25):2417. Flamm SL et al.
Clin Gastroenterol Hepatol. 2013;11(1):81.
Genotype 2 & 3
• 24 weeks of peginterferon α and non-weight
based ribavirin (800 mg/day)
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009
Genotype 4
• Plan for 48 weeks of peginterferon α and
weight based ribavirin BUT treatment should
be stopped if:
• At week 12 patient does not have at least a 2
log10 reduction in HCV RNA (EVR)
• Patient had at least a 2 log10 reduction in HCV
RNA but still has detectable HCV RNA (i.e. lacks
complete RVR) at week 12 and subsequently is
still detectable at week 24
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009
Genotype 5 and 6
•Genotype 5: Insufficient data to make
recommendations on dose and duration (?48
weeks peginterferon α and ribavirin)
•Genotype 6: 24-48 weeks of peginterferon α
and ribavirin
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009
Response Rates with
Interferon/Ribavirin
• Genotype 1: 40-50%
• Genotype 2: 80%
• Genotype 3: 80%
• Genotype 4: 50-70%
• Genotype 5: 60%
• Genotype 6: 60-80%
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009; Bisceglie AM.
Predictors of a Sustained Virologic Response Following Treatment with Peg-Interferon and Ribavirin for
Chronic Hepatitis C Infection. In: Up to Date, Basow, DS (Ed), Up to Date, Waltham, MA 2012.
What are the potential adverse effects of the standard of care
treatment?
IFN - Insomnia, Anxiety, Depression, Fatigue, hypothyroidism,
headaches, fever, muscles and body aches, poor appetite,
bitter/metallic taste, nausea and vomiting, hair loss, SOB,
neutropenia, thrombocytopenia, retinopathy, rash
Ribavirin – Fatigue, muscle inflammation, dehydration, muscle aches,
mouth sores, and dehydration, rash, nausea and vomiting,
anemia, teratogen.
Addition of telaprevir (TVR) or boceprevir (BOC) to IFN and ribavirin:
Increase in the frequency and severity of anemia
Skin disorders (rash) – mild to moderate in > 90% of the cases.
Anorectal discomfort
Drug-Drug Interactions
Dysgeusia
UptoDate
Hezode C. Boceprevir and telaprevir for the treatment of chronic hepatitis C: safety management in clinical
practice. Liver International. 2012 1478-3223
What are the risks and benefits of HCV treatment in the case of our
patient at initial presentation and at the time of the first follow-up
visit?
• Our patient falls into the category of a decompensated cirrhotic
• Benefits:
•
If patient is to undergo transplant at a future date, eradication of HCV infection pretransplant will lower the likelihood of post-transplantation infection
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Treatment of HCV 1 decompensated cirrhotics has a 13% likelihood of achieving SVR and 12/15 patients
who were HCV-RNA negative before transplant remained negative 6 months out (Everson et. al. Hepatology
2005)
May stabilize course of disease
If we hold until patient has stopped drinking and converts to a compensated cirrhotic
then SVR rates are higher
• Risks:
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Worsening or leading to hepatic decompensation and liver failure
Increased risk of infections
Flu like symptoms
Depression
Neutropenia, Anemia, and thrombocytopenia
www.aasld.org/practice guidelines: Diagnosis, Management, and Treatment of Hepatitis C 2009
Visit C- One month later
RF continued to be well until about 1 month after her follow up visit
when she started developing leg swelling, followed by increased
abdominal distention and confusion progressing over 5 days prior to
presentation. She is brought to the ED by her husband who reported
that she has not been drinking alcohol and has been taking all of her
medication as instructed. She has not had fever or chills. No cough or
shortness of breath or headache. No urinary symptoms. She has been
complaining of a mild abdominal discomfort and nausea and has a
reduced oral intake over the past 48 hours.
Vitals BP110/65, Pulse 88, RR 14, Temp 99.2
She is icteric, has a distended abdomen with flank dullness, +2 LE
edema, she opens her eyes when her name is called. She responds to
questions with an incomprehensible mumbling. Milk maid sign is
positive.
Labs
What is your interpretation of the patient’s history and physical
exam findings at presentation to the ED?
Altered mental status suggestive of hepatic encephalopathy
What is your interpretation of her
laboratory tests on presentation?
Interpretation of Laboratory Tests
on Presentation
• Progression of her liver disease as manifested
by:
• Worsening synthetic dysfunction (albumin ↓, INR
↑)
• Dilutional hyponatremia (?refractory ascites)
• Acute kidney injury (?HRS)
• Worsening bilirubin, thrombocytopenia, and
hyperkalemia
• MELD 32
What is your differential diagnosis for this acute illness? Are there
findings on her initial evaluation and testing that suggest that she is
a risk for a specific complication?
Hepatic encephalopathy – likely 2/2 infection – (SBP, UTI, PNA, etc), but other
causes can be drugs (benzos, narcotics, sedative antipsychotics, EtOH),
electrolyte – hyponatremia, hypokalemia – leading to alkalosis, hypoxia,
dehydration; excessive nitrogen load – GIB, renal failure
SBP – ascites total protein at 1.0 – current recommendation consider PPX for
patient with ascitic fluid protein concentration <1.0 g/dL, variceal hemorrhage
and a prior episode of SBP
Pathophysiology of HE
Percipients
Medications: benzo's, opiates etc.
Intestinal bleeding
Portal systemic shunts
not taking HE medications
Infections (especially SBP)
HypoNa, hypoxia, HypoK, dehydration
Renal failure
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Grades
Grade 1: euphoria, depression, mild
confusion, asterixis +/Grade 2: Lethargy, confusion, asterixis
Grade 3: Severe confusion, incoherent
language, semi-stupor but awakes to
language
Grade 4: Coma, initially can respond to
painful stimuli
•
•
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Lizardi-Cervera et. al. Hepatic encephalopathy: A review. Annals of Hepatology 2003; 2(3): July-September. 122-130
What are your initial steps in management?
• Paracentesis and send for cell count with
differential and culture
•
If + SBP would start on Ceftriaxone 1gm
• Send blood cultures, U/A, urine cultures, CXR
• Place NGT and give lactulose
• Review medication list to ensure no precipitants of
HE are present
• Evaluate renal dysfunction (pre-renal vs. HRS)
•
IV albumin challenge and hold diuretics
• Vitamin K
• RUQ ultrasound with dopplers
Assuming that, after an initial diagnostic evaluation and
treatment, three days after the initial presentation, her mental
status is improved, bilirubin is reduced to 4.0 and INR to 1.7, but
Creatinine continues to rise and is now 3.6. She is making about
80 cc of urine per day. How would you evaluate the renal
further? What are the next steps in management?
•
•
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FeNa
Renal ultrasound
Octreotide with a target dose of 200 g SC tid
Midodrine titrated up to a maximum of 12.5 mg orally
three times per day to achieve an increase in mean blood
pressure of 15 mm Hg
Runyon, Bruce. Management of Adult Patients with Ascites Due to Cirrhosis: An Update. HEPATOLOGY, Vol. 49, No. 6, 2009
Renal Failure in Cirrhotics
Pere Ginès et al Hepatorenal syndrome. The Lancet. Volume 362, Issue 9398, 29 November 2003, Pages 1819–1827
Major Diagnostic criteria for Hepatorenal Syndrome
• Cirrhosis with ascites
• Serum creatinine >1.5 mg/dL
• No improvement of serum creatinine (decrease to a level of
1.5 mg/dL or less) after at least 2 days with diuretic
withdrawal and volume expansion with albumin
• The recommended dose of albumin is 1 g/kg body weight/day up to a
maximum of 100 g/day)
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•
•
Absence of shock
No current or recent treatment with nephrotoxic drugs
Absence of parenchymal kidney disease as indicated by
proteinuria < 500 mg/day, microhematuria (50 red blood cells
per high power field), and/or abnormal renal ultrasonograph
Runyon, Bruce. Management of Adult Patients with Ascites Due to Cirrhosis: An Update. HEPATOLOGY, Vol. 49, No. 6, 2009
Hepatorenal Syndrome
• Type I: rapidly progressive reduction in renal function as
defined by a doubling of the initial serum creatinine to a level
> 2.5 mg/dL or a 50% reduction of the initial 24-hour
creatinine clearance to a level < 20 mL/minute in less than 2
weeks
• Type II does not have a rapidly progressive course
Runyon, Bruce. Management of Adult Patients with Ascites Due to Cirrhosis: An Update. HEPATOLOGY, Vol. 49, No. 6, 2009
Hepatorenal Syndrome Pathophysiology
Liver transplant
TIPS
Vasoconstrictor
Albumin
Meyer, Markus. Vasopressin analogues in the treatment of hepatorenal syndrome and gastrointestinal haemorrhage.
Best Practice & Research Clinical Anaesthesiology Volume 22, Issue 2, June 2008, Pages 335–350
What is her long term prognosis, and how does this
affect your management decisions?
• Given decompensated cirrhosis and MELD≥21, median
survival < 6 months, three month mortality is 52.6%
• Liver transplant evaluation (~ 3 months since last alcoholic
beverage)
• No history of CKD, so would not consider combined renal and
liver transplant
• If persistent worsening of renal function and liver transplant
candidate, consider IHD
Salpeter SL et al. Am J Med. 2012 May;125(5):512.e1-6. Weisner R et al. Model for End Stage
Liver Disease (MELD) and Allocation of Donor Livers. Gastroenterology. 2003; 124: 91-96.
Long Term Prognosis
Weisner R et al. Model for End Stage
Liver Disease (MELD) and Allocation of Donor Livers. Gastroenterology. 2003; 124: 91-96.

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