Download Chronic liver disease Compensated cirrhosis Decompensated

Clinical Pathological Conference
Mack C. Mitchell, Jr., M.D.
Johns Hopkins Bayview
Medical Center
February 2, 2010
Questions to address
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What is the most likely etiology of her
liver disease?
What is the most likely cause of death?
Process of Differential Diagnosis
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Collecting the facts
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Clinical history
Physical examination
Ancillary examinations (lab and imaging)
Observation of the course of illness
Analyzing the facts
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Critically evaluate data
Select 2 or 3 central features
List diseases in which the features are encountered
Reach final diagnosis by selecting the best fit
Review all the evidence with final diagnosis in mind
Chief complaint
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54 y.o woman with 2-3 yr h/o cirrhosis
and several days increased lethargy
History of present illness
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2-3 yr h/o cirrhosis with diuretic
refractory ascites requiring monthly
large volume paracentesis
3 days before admission, large volume
paracentesis
Increased lethargy and confusion the
following day; symptoms progressed
despite increased doses of lactulose
Past medical/surgical history
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Cirrhosis diagnosed 3 yrs ago after
development of ascites and easy bruising
 No viral or autoimmune markers
 Normal iron saturation
 No history of alcohol consumption, drug or
toxin exposure
 Possible portopulmonary hypertension
Obesity and type 2 diabetes > 20 yrs, insulin
therapy > 15 yrs (? Compliance)
Chronic kidney disease, baseline creat 1.4
Past history (cont)
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Monthly large vol paracentesis for 2 yrs
No h/o variceal bleeding
Few episodes of encephalopathy treated with
protein restriction and lactulose
Irrelevant data
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H/O neck abscess
H/O C-section
H/O ingrown toenail age 9
Social history
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Medically disabled due to liver disease
Active member of Jehovah’s Witness
church
Lifetime non-smoker and non-drinker
Divorced, 2 children
Family history
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Mother died of complications of
diabetes in her late 50’s
Otherwise non-contributory
Medications on admission
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Furosemide
Spironolactone
Lactulose
Metronidazole
Pantoprazole
Propranolol
Darbopoietin (erythropoietin) injection
Idiopathic or “cryptogenic”
cirrhosis
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Cirrhosis of unknown etiology without
history of alcohol consumption or viral
hepatitis
Includes numerous conditions
Differential diagnosis of
cryptogenic cirrhosis
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NAFLD/NASH
Hemochromatosis
Alpha 1 anti-trypsin
deficiency
Wilson disease
Type IV glycogen
storage disease
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Chronic right heart
failure
Constrictive pericarditis
Budd-Chiari syndrome
Sarcoidosis
Sclerosing cholangitis
Autoimmune hepatitis
Primary biliary cirrhosis
Questions for physical exam
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Evidence of right heart failure
Evidence of chronic lung disease
Evidence of vasculitis or other
autoimmune features (CRST in PBC)
Splenomegaly? Hepatomegaly?
Ascites?
Physical examination
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BP 80/46; P 112; R 26; T 97.8; Wt 115 kg
Difficult to arouse, oriented only to
person; asterixis
Scleral icterus
Tense ascites, peripheral edema
No hepatosplenomegaly
3/6 murmur left upper sternal border, no
JVD
Analyzing the facts
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Long history of diabetes, obesity
Recent deterioration with confusion,
lethargy
Physical findings of ascites, jaundice
and III/VI systolic murmur in
pulmonic/tricuspid valve area
Differential diagnosis of
cryptogenic cirrhosis
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NAFLD/NASH
Hemochromatosis
Alpha 1 anti-trypsin
deficiency
Wilson disease
Type IV glycogen
storage disease
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Chronic right heart
failure
Constrictive pericarditis
Budd-Chiari syndrome
Sarcoidosis
Sclerosing cholangitis
Autoimmune hepatitis
Primary biliary cirrhosis
Laboratory findings
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WBC 16,700; left shift 80% polys, 12%
bands
Hct 34% (baseline 28%)
Platelets 71,000
T. bili 6.0; AST169; ALT 43; Alk phos
251, ammonia 39
pO2 110 (2 l FIO2); pCO2 30; pH 7.24
Imaging results
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Nodular liver
Ascites
No evidence of mass within liver
Previous echocardiogram estimated
RVSP of 56
Prevalence of Chronic Liver Disorders
in the United States
Percentage of population
Nonalcoholic Fatty
Liver Disorder
20
2.5
Nonalcoholic
steatohepatitis
Chronic Hepatitis C
2
Alcoholic Liver Disease
0.7
Hemochromatosis
0.5
Chronic Hepatitis B
0.4
0
5
10
15
Percent of Population
20
25
Predictors of NASH
NASH is Likely in Those with More Components of MS
% NASH
75
50
25
0
Neither
HTN
Villanova et al. Hepatology 2005.
DM
Both
Predictors of Fibrosis in NAFLD
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Liver biopsies performed in 144 pts with
NAFLD
Multivariate analysis indicated 4
variables which were significant:
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Age > 45 (Odds ratio 5.6)
BMI > 30 (Odds ratio 4.3)
Diabetes mellitus (Odds ratio 3.5)
AST/ALT ratio > 1 (Odds ratio 4.3)
Angulo, et al. Hepatology
30:1356, 1999
Pulmonary complications in
cirrhosis
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Portopulmonary hypertension (POPH) is the
elevation of pulmonary artery pressure due to
increased resistance to pulmonary blood flow
in the setting of portal hypertension.
Hepatopulmonary syndrome is characterized
by a defect in arterial oxygenation induced by
pulmonary vascular dilatation in the setting of
chronic liver disease.
What is the cause of cirrhosis?
Based on history of obesity and diabetes
and absence of other causes, NAFLD is
most likely. A1AT phenotype could be
checked. Elevated pulmonary pressures are
most likely secondary rather than primary.
What is cause of death?
Bleeding
Infection
Hepatorenal syndrome
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Development of
complications:
Variceal hemorrhage
Ascites
Encephalopathy
Jaundice
Death
Decompensation shortens survival
80%
Median survival
~ 9 years
All patients
with cirrhosis
Probability
of survival
40%
Decompensated Median survival
~ 1.6 years
cirrhosis
60
Gines et. al., Hepatology 1987;7:122
120
Months
180
Causes of death in cirrhosis
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Infections: SBP, UTI, pneumonia, bacteremia
related to procedures, spontaneous
Bleeding: varices, other
Hepatorenal syndrome: type I –oliguric renal
failure in absence of hypovolemia
Hepatocellular carcinoma
“Liver failure”—metabolic failure often due to
one of above
Hepatorenal syndrome
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Often develops as a “pre-terminal”
event precipitated by infection or
bleeding
Pathophysiology related to “systemic”
arterial vasodilatation leading to
ineffective plasma volume with renal
arterial vasoconstriction and avid
sodium retention
Circulatory dysfunction
induced by paracentesis
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Occurs after large volume paracentesis
(usually > 5 liters)
Worsening vasodilatation
Hyponatremia
Activation of renin/angio/aldo system
Azotemia
Prevented by administration of albumin
Careful re-review of labs
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Elevated WBC, 16,700 (usual WBC is only
3500-5000 in cirrhosis)
Elevated BUN/creat ratio (BUN is usually low
in cirrhosis)
Elevated Hct above baseline
Metabolic acidosis (pH 7.24)
Patient has volume depletion and evidence of
infection, despite absence of fever
Additional diagnostic tests to
consider
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Analysis of ascitic fluid, particularly cell
count and differential
Alpha fetoprotein
Approach to management of
“acute on chronic” liver failure
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Plasma volume expansion with albumin,
rather than crystalloid
Vasopressor therapy—constricts peripheral
arteries
Antibiotics if evidence of infection, albumin
improves survival in SBP
Encephalopathy does not usually improve
with increased doses of lactulose
Volume replacement for hemorrhage
Cause of death?
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Infection, possibly peritonitis
Volume depletion probably due to large volume
paracentesis
These two factors occurred in setting of
advanced cirrhosis, with pre-existing
abnormalities in vascular tone leading to
hypotension and compromised hepatocellular
function leading to encepthalopathy, acidosis
and coagulopathy