Chronic Liver Disease
Burden
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Markedly decreased life expectancy
12th leading cause of death in US
25,000 deaths annually in US
High morbidity and mortality due to
complications
Autoimmune hepatitis
Alcoholic liver disease
Chronic hepatitis C
Primary sclerosing cholangitis
Chronic hepatitis B
Alpha1-antitrypsin deficiency
Wilson’s disease
Primary biliary cirrhosis
Hereditary hemochromatosis
Hepatic Fibrosis
Cirrhosis
Hepatic fibrosis
• Fibrosis is a wound healing response in which
damaged regions are encapsulated by an
extracellular matrix or scar
• Develops in almost all patients with chronic
liver injury
Cirrhosis
• Late stage of progressive hepatic fibrosis
• Generally irreversible in advanced stages
LFT’s
• LFT is a misleading term
– Does not reflect how well the liver is functioning
– Abnormal values can be caused by non-hepatic
diseases
LFT’s
• Enzyme tests: AST, ALT, Alk Phos and GGT
• Hepatic Function: Albumin and PT and
Indirect bilirubin
• Hepatic transport ability (biliary system):
Direct Bilirubin
Patterns
• Disproportionate elevation of transaminases
seen with hepatocellular processes
• Disproportionate elevation of Alk Phos seen in
cholestatic process
• Serum Bilirubin can be elevated in both
processes, so need to look at direct vs indirect
bilirubin to differentiate
Patterns
• Low albumin suggests chronic process
• Normal albumin suggests acute process
• Elevated PT/INR is either Vit K deficiency (due
to malabsorption of Vit K) or significant
hepatocellular dysfunction (inability to make
coagulation factors)
• Failure of parenteral Vit K to correct PT
indicates significant hepatocellular dysfunction
(inability to make coagulation factors).
• Patients who lack an apparent cause for
cirrhosis should be questioned about lifetime
body weight because nonalcoholic
steatohepatitis (NASH) has been concluded to
be causative in many patients.
•Ascites
• What do we do when a patient presents with
ascites for the first time?
• The cause of new ascites should be evaluated
by doing a paracentesis.
• What does a bloody ascitic fluid suggest?
• Tumor
• What does a cloudy ascitic fluid suggest?
• Infection
• What does a milky ascitic fluid suggest?
• Lymphatic obstruction
• Approximately 1,500cc of fluid must be
present in the abdomen before flank dullness
is detected on percussion.
• The fluid wave is not a useful sign but shifting
dullness is.
• What is the most common cause of ascites in
United States?
• 85% of patients with ascites in the United
States have cirrhosis
• What are the tests that we order on the
ascites fluid obtained by paracentesis?
• IF uncomplicated cirrhosis ascites is
suspected, only cell count and differential,
albumin, and total protein concentration are
performed on the initial specimen.
• If ascitic fluid infection is suspected (fever,
abdominal pain, elevated cell count or
unexplained encephalopathy), bacterial
culture in blood culture bottles should be
performed.
• What can we do to determine the cause of
ascites after the ascitic fluid labs are back?
Serum-to ascites albumin gradient
(SAAG)
• SAAG= (serum albumin)-(ascitic fluid
albumin)
• SAAG > 1.1 indicates portal HTN
• SAAG < 1.1 indicates pt does not have
portal HTN
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SAAG >1.1 (portal HTN):
Cirrhosis
Right heart failure
Fulminant liver failure (which also includes
“massive hepatic metastasis”)
- Budd-Chiari syndrome
- myxedema
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SAAG<1.1:
TB peritonitis
Nephrotic syndrome
Pancreatitis
Peritoneal carcinomatosis
• Elevated ascites protein level >=2.5 is seen in
all cases of SAAG<1.1 but also in right heart
failure.
• Ascites PMN count >250 is infection until
proven otherwise.
- Do bacterial culture in “blood culture bottles”
- Is considered to be spontaneous bacterial
peritonitis (SBP) if there is no evidence of
intra-abdominal, surgical treatable source of
infection (secondary bacterial peritonitis).
• Most of the bacterial cultures of ascitic fluids
with PMN>250 will grow bacteria if:
1) The fluid is cultured in two blood culture bottles
2) There has been no prior antibiotic treatment
and
3) There is no other explanation for an elevated
PMN count (e.g. hemorrhagic ascites,
peritoneal carcinomatosis, pancreatitis, or
peritoneal TB).
• Patients who meet the criteria explained on
the previous slide but have negative cultures
have been labeled with diagnosis of “culturenegative neutrocytic ascites and should be
treated as if they have SBP due to similar
mortality as SBP if not treated as such.
Diagnosis of SBP
• Definition: ascitic fluid infection w/o intraabdominal source of infection
• Positive ascitic fluid culture and/or PMN>250
• Consider secondary bacterial peritonitis if at least
two of the following:
– TP >1.0
– Glucose <50
– LDH > upper limit for serum
AND multiple organisms growing on gram stain or
culture.
AND PMN >250 (sometimes in thousands).
Antibiotic choice
• Need to cover gut flora as well as Strep and Staph
• 3rd generation cephalosporin such as cefotaxime 2g
IV q8hrs
• Treat for 5 days and reassess patient
– If has had good response, d/c antibiotics
– If still has fever or abd pain, re-tap
• PMN <250, stop antibiotics
• PMN > pre-treatment level, look for surgical cause
• PMN >250 but < pre-treatment level, give 48 hrs antibiotocs and
repeat tap
SBP Prophylaxis
• Indicated for patients with h/o SBP or variceal
bleed
• Proven to decrease mortality, to prevent
bacterial infections, and to be cost effective
SBP Prophylaxis Regimens
• If h/o SBP, Norfloxacin 400 mg qweek or
Bactrim DS qday
• If recent variceal bleed, Norfloxacin 400 mg
BID or Bactrim DS BID for 7 days
Treatment of ascites of liver disease
• Goal is to minimize edema and ascites w/o
intravascular volume depletion
• No evidence that treatment of ascites
improves survival, but pt’s feel better
• Treat underlying disorder (eg: Alcohol
cessation for alcoholic cirrhosis)
• Avoid NSAID’s
• Limit Na to 2g/day
Treatment of ascites of liver disease
(continued)
• It is Na restriction and not fluid restriction that
results in weight loss
• Fluid restriction is not necessary in treating most
patients with cirrhosis or ascites
• Do not attempt to correct the chronic
hyponatremia (which is seen often in cirrhotic
patients with ascites) unless <120-125 since
attempts to rapidly correct hyponatremia with
saline can lead to more complications than the
hyponatremia itself.
Treatment of ascites of liver disease
(continued)
• Start with combination of spironolactone and
furosemide (100 mg and 40mg) or spironolactone
alone
• Max required doses: spironolactone 400mg/d and
furosemide 160 mg/d
• If using combination of spironolactone and furosemide,
keep spironolactone to furosemide ratio at
100mg/40mg
• Required wt loss is 300-500g/day without massive
edema and 800-1000g/day or more with massive
edema
• Oral furosemide is preferred over iv furosemide.
Treatment of ascites of liver disease
(continued)
• Do fluid restriction if sodium <120.
• Any of the following should lead to cessation
of diuretics:
- Encephalopathy
- Serum NA <120 despite fluid restriction
- Serum creatinine >2.0.
Treatment of large volume ascites
• Treatment of choice is large volume
paracentesis:
- Faster, more effective and fewer adverse
effects than diuresis
- Diuretics should be given as maintenance
therapy to prevent recurrence
Refractory Ascites in liver disease
• <10% of ascites
• Defined as fluid overload that:
1) Is unresponsive to Na-restricted diet and
high-dose diuretic treatment (400mg/day of
spironolactone and 160mg/day of
furosemide)
OR
2) Recurs rapidly after therapeutic paracentesis.
Treatment of refractory ascites in liver
disease
• Options:
1) Serial therapeutic paracentesis
2) Liver transplantation
3) Transjugular intrahepatic portasystemic
stent-shunt (TIPS)
4) Peritoneovenous shunt (rarely done)
• Referal for liver transplant should not be
delayed.
Complications of cirrhosis
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Variceal hemorrhage
Ascites
Spontaneous bacterial peritonitis
Hepatorenal syndrome
Hepatic encephalopahty
Hepatopulmonary syndrome
Hepatocellular carcinoma
• All patients with chronic liver disease should
be checked for hepatitis viral panel, especially
for hepatits B and C.
• Vaccination should be given for hepatitis A
and B vaccination if they are negative for
these types of hepatitis.
• The liver is commonly imaged (usually with
Ultrasound) in a patient with cirrhosis with or
without ascites. Why?
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To screen for:
Hepatocellular carcinoma
Portal vein thrombosis
Hepatic vein thrombosis
Case
• 55 yo man with h/o heavy ETOH use presents with
abdominal swelling and pain
• What other questions would you ask the patient?
• What are you looking for on your exam?
Case
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AST 150, ALT 73, alk phos 153, GGT 320
Bilirubin 4.3, Indirect bilirubin 3.1
TP 8.3
Albumin 2.2
INR 1.9
WBC 2.2, H/H 11/33. Plt 78K
Na 130
What would you do first in the
evaluation of this patient??
Paracentesis
• What information do you get from peritoneal
fluid analysis?
• What studies do you want to perform on the
ascites fluid?
Ascitic fluid
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Cloudy fluid
Albumin 0.5
TP 0.7
Cell count: 425 WBC, 90% PMN’s
Gram stain: many PMN’s, no bacteria
How do you interpret the results
from your tap?
How will you treat the ascites?