Chronic Liver Disease

Burden

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
Wilsons 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

LFTs
LFT is a misleading term
Does not reflect how well the liver is
functioning
Abnormal values can be caused by nonhepatic diseases

LFTs
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

SAAG >1.1 (portal HTN):

Cirrhosis
Right heart failure
Fulminant liver failure (which also
includes massive hepatic
metastasis)
- Budd-Chiari syndrome
- myxedema

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 pts feel better
Treat underlying disorder (eg: Alcohol
cessation for alcoholic cirrhosis)
Avoid NSAIDs
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

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?

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
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

Cloudy fluid
Albumin 0.5
TP 0.7
Cell count: 425 WBC, 90% PMNs
Gram stain: many PMNs, no
bacteria

How do you interpret the results from

your tap?

How will you treat the

ascites?