Ascites

ASCITES
PHUNG HUY HOANG, MD
Resident in Internal Medicine
Pham Ngoc Thach University of Medicine
September 2017

Ascitic fluid
analysis
PHUNG HUY HOANG, MD
September 2017

Cesario K. B., Choure A., Carey W. D. Cirrhotic Ascites. 2013 [cited 2017 June]

• The opacity of many cloudy ascitic fluid specimens: neutrophils  shimmering effect: glass
tube containing the fluid is rocked back and forth in front of a light
• Transparent and usually slightly yellow: Non-neutrocytic (i.e., ascitic fluid PMN count <
250/mm3)
• Nearly clear: absolute neutrophil count < 1000/mm3
• Quite cloudy: > 5000/mm3
• Frankly purulent: > 50000/mm3 (gross intraabdominal infection e.g secondary peritonitis or an
abscess)  diferrential milky fluid!  Lack of odor and TG >200 mg/dL: chylous ascites
• No pigment and look like water: very low protein concentration
GROSS APPEARANCE (1)

• Threshold for a pink appearance: RBC count of 10000/mm3
• Distinctly red: > 20000/mm3
Fuid specimens: bloody
• Traumatic tap (blood-streaked, frequently clot unless the ﬂuid is transferred
immediately to the anticoagulant-containing tube for the cell count)
• Nontraumatic (bloody hepatic lymph/portal hypertension, malignancy, TB/rare)
or remotely traumatic blood-tinged ascitic ﬂuid: homogeneous and not clot
(already clotted and the clot has lysed)

• Ascitic fluid frequently is lipid-laden, lipid opacifes the fluid
• Most opaque, milky fluid samples (chylous ascite): TG (triglyceride) > 200 mg/dL (2.26
mmol/L) and usually > 1000 mg/dL (11.30 mmol/L)  creamy layer will separate
• Dilute skim milk: TG = 100-200 mg/dL (1.13-2.26 mmol/L)
• Dark-brown fluid (with a bilirubin concentration > serum): biliary perforation (Deeply
jaundiced patients: bile-stained ascitic fluid, but level and the degree of pigmentation < serum)
• Tea-colored to jet black: Pancreatic ascites: may be pigmented (effect of pancreatic enzymes
on RBCs)
• Black ascitic fluid: malignant melanoma
Runyon B. A. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 1553-1576
Runyon B. A. (1987), J Clin Gastroenterol, 9 (5), pp. 543-5

Runyon B. A. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark
Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp.
1553-1576

• The WBC count in uncomplicated ascites/cirrhosis: usually < 500/mm3
• ULN for absolute PMN count in uncomplicated ascitic fluid/cirrhosis < 250/mm3
• Any inflammatory process can result in an elevated ascitic fluid WBC count:
• Spontaneous bacterial peritonitis (SPB): most common  predominant PMN
• Tuberculous peritonitis and peritoneal carcinomatosis  predominant lymphocytes
• Leakage of blood into the peritoneal cavity (slightly traumatic tap):  ascitic fluid WBC,
PMN count (neutrophils predominate in blood)  corrected PMN/ascite fluid
1 PMN is subtracted from the absolute ascitic fluid PMN count for every 250 RBCs
CELL COUNT (1)

• During diuresis/cirrhosis and ascites: WBC count can concentrate to > 1000/mm3  requires
prediuresis count, normal lymphocytes predominate, unexplained clinical symptoms or signs
(e.g., fever or abdominal pain) be absent
• Short survival of PMNs: relative stability of the absolute PMN count during diuresis  cutoff
value remains reliable
• Some laboratories count mesothelial cells in addition to WBCs and label the sum as
“nucleated cells”
• Malignancy-related ascites may also  PMN count (16% of cases in one series) (dying tumor
cells attract neutrophils), predominance of lymphocytes
CELL COUNT (2)

• Before the 1980s: total protein to classify ascites as either exudative or transudative (cut-off
2.5 g/dL [25 g/L])  not careful defined and validated.
• The serum-ascites albumin gradient (SAAG): proved to categorize ascites better, reflection
of hepatic sinusoidal pressure
• SAAG: not explain the pathogenesis of ascites formation, nor does it explain where the
albumin came from (liver or bowel)
• Oncotic-hydrostatic balance (Starling forces), difference between the serum and ascitic fluid
albumin concentrations correlates directly with portal pressure.
• The accuracy of the test is excellent (even with ascitic fluid infection, diuresis, therapeutic
paracentesis, IV infusions of albumin, and various causes of liver disease)
Runyon B. A., Montano A. A., Akriviadis E. A., et al. (1992), Ann Intern Med, 117 (3), pp. 215-20.
SERUM-ASCITE ALBUMIN GRADIENT (SAAG) (1)

Runyon B. A. (2012), Schiff's Diseases of the Liver, Eugene R. Schiff, Willis C. Maddrey, Michael F. Sorrell, Editors, Wiley Blackwell, pp. 393-420.

• SAAG = serum albumin - ascitic albumin
• ≥ 1.1 g/dL (11g/L) = high albumin gradient: portal hypertension
• < 1.1 g/dL (11g/L) = low albumin gradient: unlikely to have portal hypertension
• If the first result is borderline (e.g., 1.0 or 1.1 g/dL [10 or 11 g/L])  repeating the
paracentesis and analysis usually provides a definitive result
• SAAG correlates very well with the hepatic venous pressure gradient (r = 0.72)
Hoefs J. C. (1983), J Lab Clin Med, 102 (2), pp. 260-73

FALSE VALUE (1)
• The accuracy of the SAAG reduced: specimens of serum and ascites are not obtained nearly
simultaneously (should be same day, preferably same hour).
• Both serum and ascitic ﬂuid albumin concentrations change over time; however parallel 
difference is stable.
• Arterial hypotension:  portal pressure and a narrowing of the SAAG.

FALSE VALUE (2)
• Lipid interferes with the assay for albumin, and chylous ascites may result in a falsely high
SAAG
• The accuracy of the albumin assay at low albumin concentrations (e.g., <1 g/dL [10 g/L])
should be confirmed (If serum albumin < 1.1 g/dL/ascitic cirrhosis, the SAAG will be falsely low)
• Serum hyperglobulinemia (serum globulin level > 5 g/dL [50 g/L])  high ascitic ﬂuid globulin
concentration  narrow the albumin gradient (contributing to the oncotic forces)
Corrected SAAG = uncorrected SAAG x 0.16 x serum globulin (g/dL) + 2.5
SERUM-ASCITE ALBUMIN GRADIENT (SAAG)

ADA, adenosine deaminase; AFB, acid-fast bacilli; Asc prot, ascites total protein levels; CT, computed tomography; CUS, cardiac
echosonography; HVPG, hepatic venous pressure gradient; SAAG, serum–ascites albumin gradient; TJLB, transjugular liver biopsy
Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology,
Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors,
Wiley Blackwell, pp. 2087-2106

• Determine susceptibility of developing bacterial infection
• Cirrhotic patients with an ascites protein <1.0 g/dL1 or <1.5 g/dL2 have a higher risk of
developing infection (SBP)
• Ascites does NOT become an “exudate” with infection (≠ pleura) = ascitic ﬂuid total protein
concentration does not increase during SBP1,3
•  in peritoneal processes (leakage of high protein mesenteric lymph from obstructed lymphatics
and/or from an inﬂamed peritoneal surface)
• Exudative ascites is also present in ascites secondary to heart failure
 high or low total ascitic protein level to categorize
1. Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 2087-2106
2. EASL (2010), J Hepatol, 53 (3), pp. 397-417
3. Runyon B. A. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 1553-
1576
PROTEIN

Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 2087-2106

• Small enough to diffuse readily intobody fluid cavities  concentration of glucose in ascitic
fluid = in serum (unless glucose being consumed by ascitic fluid WBCs or bacteria)
• Ascitic fluid glucose in early detected SBP is similar to that of sterile fluid
Runyon B. A., Hoefs J. C. (1985), Hepatology, 5 (2), pp. 257-9
GLUCOSE

• Too large to enter ascitic ﬂuid readily from blood  usually is less than half of the serum level
in uncomplicated ascites/cirrhosis
• In SBP: LDH  because of the release of LDH from neutrophils  ascitic ﬂuid concentration >
serum
• Secondary peritonitis, the LDH level is even > in SBP and may be several-fold higher than
the serum LDH level
LACTATE DEHYDROGENASE

Runyon B. A. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark
Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 1553-
1576

• Most common bacterial infection of ascitic ﬂuid: SBP (monomicrobial, with a low bacterial
concentration median colony count of only 1 organism/mL)
• SBP: more like bacteremia (number of bacteria present)  culturing ascitic ﬂuid as if it were
blood has a high yield  superiority of the blood culture bottle method + bedside
inoculation
• Gene probes: commercially available for the detection of bacteremia
• 50% of the cultures are still negative
• Simultaneous blood cultures should be collected (30%–58% of SBP cases are associated
with bacteremia)
• Gram stain: positive in < a third of the cases of SBP
Runyon B. A., AASLD (2013), Hepatology, 57 (4), pp. 1651-3
Runyon B. A., Canawati H. N., Akriviadis E. A. (1988), Gastroenterology, 95 (5), pp. 1351-5
SMEAR AND CULTURE

• A direct smear of ascitic ﬂuid to detect mycobacteria: almost never positive (~3%) (rarity of
tuberculous peritonitis, low concentration of mycobacteria in ascitic ﬂuid in tuberculous peritonitis)
• Conventional culture media: 4–8 weeks to detect AFB
• Cultures: determine susceptibility to antimicrobial agents
• Mycobacterium culture: 50% sensitive
 laparoscopy with histology and culture of peritoneal biopsies has a sensitivity approaching
100%
• DNA probes
Hillebrand D. J., Runyon B. A., Yasmineh W. G., et al. (1996), Hepatology, 24 (6), pp. 1408-12
SMEAR AND CULTURE FOR TB

• Enzyme related to proliferation and differentiation of lymphocytes
• Appears to be a fast and discriminating test for diagnosis PTB
• Recommended in suspected PTB, esp endemic areas
• Cut-off values from 36 to 40 IU/L with an optimal cut-off point of 39 IU/L
Riquelme A., Calvo M., Salech F., et al. (2006), J Clin Gastroenterol, 40 (8), pp. 705-10
ADENOSIN DEAMINASE

• Only 58–75% sensitive in detecting “malignant ascites” (when tumor cells line the peritoneal
cavity)
• Patients with peritoneal carcinomatosis have viable malignant cells exfoliating into ascitic fluid
 these cells detected in their ascitic fluid cytologies
• DNA cytometry  improve the sensitivity of effusion cell analysis to 95%
Runyon B. A. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S.
Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 1553-1576
CYTOLOGY

• The bilirubin concentration should be measured in ascitic fluid that is dark brown
• Ascitic fluid bilirubin > 6 mg/dL (102 µmol/L) and > serum level  suggests biliary or proximal
small intestinal perforation into ascitic fluid
Runyon B. A. (1987), J Clin Gastroenterol, 9 (5), pp. 543-5
Akriviadis E. A., Runyon B. A. (1990), Gastroenterology, 98 (1), pp. 127-33
BILIRUBIN

• Should be measured in opalescent or frankly milky ascitic ﬂuid
• Accumulation of peritoneal ﬂuid rich in triglycerides  presence of lymph in the abdominal
cavity
• Chylous ascites = TG > 200 mg/dL (2.26 mmol/L) and > serum level; usually, the level is
greater than 1000 mg/dL (11.30 mmol/L)
TRIGLYCERIDE (1)

• Pathogenesis
• Disruption of the lymphatic system/obstruction (malignant infltration or inﬂammatory)
• Traumatic injury (surgery, trauma)
• Altered hemodynamics   caval (constrictive pericarditis) and hepatic venous pressures
(cirrhosis)  increased formation of hepatic duct lymph.
• SAAG may be falsely elevated in chylous ascites
• Lymphangiography and lymphoscintigraphy
TRIGLYCERIDE (2)

• pH
• Lactate
• Fibronectin
• Cholesterol
• CEA
• α1-antitrypsin
• Cyclic adenosine monophosphate
• (cAMP)
• Glycosaminoglycans
Runyon B. A., AASLD (2013), Hepatology, 57 (4), pp. 1651-3
UNUSEFUL TESTS

Approach and
management
PHUNG HUY HOANG, MD
September 2017

INTRODUCTION
• Ascites: pathologic accumulation of ﬂuid in peritoneal cavity
• Greek “askos”: a leather bag used to carry wine, water, or oil
• Most common cause: cirrhosis
• Most common first decompensating event1
• Carries the highest mortality2
• Approach to a patient with ascites depends on the setting surrounding its presentation
1. D'Amico G., Garcia-Tsao G., Pagliaro L. (2006), Journal of Hepatology, 44 (1), pp. 217-231
2. Bruno S., Saibeni S., Bagnardi V., et al. (2013), Am J Gastroenterol, 108 (7), pp. 1112-1122

Burroughs A., Westaby D. (2012), Kumar & Clark’s Clinical Medicine, Parveen Kumar , Michael Clark, Editors, Elsevier, pp. 303-370

Garcia-Tsao G. (2018), Zakim and Boyer’s Hepatology: A Textbook of Liver Disease, Arun J. Sanyal, et al., Editors, Elsevier, pp. 220-232

ETIOLOGY
• Cirrhotic
• Noncirrhotic
• Other parenchymal liver diseases
• Malignancy: peritoneal carcinomatosis (gynecological tumors, gastric carcinoma,
extensive liver metastases)
• Cardiovascular: CHF, constrictive or restrictive cardiomyopathy, pericardial disease
rhrombosis of inferior vena cava, BCS, veno-occlusive disease
• Infection: TB, Fitz–Hugh–Curtis syndrome (chlamydiae, gonococci), coccidioidomycosis,
Whipple’s disease
• Renal: nephrotic syndrome, uremia, hemodialysis
• Pancreatic

PATHOGENESIS
1. Increase hydrostatic pressure (cirrhosis, BCS, IVC thrombosis, CHF, pericardial disease,
cardiomyopathy, CKD)
2. Decrease osmotic pressure: decrease serum albumin (cirrhosis, nephrotic syndrome,
malnutrition)
3. Increase vascular permeability (TB, peritoneal bacteritis, malignancy, seroritis/connective
tissue disease)
4. Fluid leak into peritonium (pancreatic, biliary, chylous, urinary)

Doig A. K., Huether S. E. (2014), Pathophysiology the Biologic Basis for Disease in Adults and Children, Kathryn L. McCance , Sue E. Huether, Editors, Elsevier, pp. 1423-1485

APPROACH TO PATIENTS
Definitive diagnosis of ascites
Identify etiology and complications
• History and physical examination
• Imaging
• Paracentesis1,2
• Inpatients and outpatients with clinically apparent new-onset ascites
• All patients hospitalized for worsening of ascites or any complication of cirrhosis
1. EASL (2010), J Hepatol, 53 (3), pp. 397-417
2. Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107.

•  abdominal girth, weight gain
• Bulging flanks, flank dullness, shifing dullness (most sensitive finding in the clinical
diagnosis), fluid wave, “puddle sign”: >1000 mL
• Presence of spider angiomas, palmar erythema, muscle wasting, jaundice and/or signs of
portal hypertension (splenomegaly, abdominal wall collaterals): cirrhosis?
• Distended neck veins, S3 gallop, uniform hepatomegaly with hepatojugular reflux, peripheral
edema: CHF?
• Small nodule at umbilicus (Sister Joseph Mary nodule), enlarged supraclavicular lymph node
(Virchow node): malignant?
• Large veins with upward flow localized in the back: obstruction of IVC?
HISTORY AND PHYSICAL EXAMINATION

Albano E. A., Kanter J. (2005), New England Journal of Medicine, 352 (18), pp. 1913-1913

MacGilchrist A., Iredale J., Parks R. (2013), Macleod’s Clinical Examination, Graham Douglas, Fiona Nicol, Colin Robertson, Editors, Churchill Livinstone, pp. 165-194

Bickley L. S., Szilagyi P. G. (2013), Bates’ Guide To Physical Examination and History-Taking, Wolters Kluwer, pp. 433-488

Epstein O., Perkin G. D., Cookson J., et al. (2009), Pocket Guide to Clinical Examination, Mosby Elsevier, pp. 139-168

• 1+: detectable only by careful examination.
• 2+: easily detected but of relatively small volume.
• 3+: obvious ascites but not tense.
• 4+: tense ascites
QUANTIFICATION
Runyon B. A. (2012), Schiff’s Diseases of the Liver, Eugene R. Schiff, Willis C. Maddrey, Michael F. Sorrell, Editors, Wiley-Blackwell, pp. 393-420

• ABDOMINAL US:
• Initial, least invasive, and most cost-eﬀective = “GOLD STANDARD” for diagnosis of
ascites
• > 100mL
• Locating optimal site to perform paracentesis (small amount, or loculated ascites)
• Examination of hepatic venous system
• CT SCAN:
• More sensitive than US in determining cirrhosis or malignancy
• Finding a small nodular liver, splenomegaly, and collaterals
IMAGING

THERAPEUTICS FOR CIRRHOTIC ASCITES
• Liver transplantation: ultimate treatment for ascites and its complications
• Sodium restriction and diuretics
• Therapeutic paracentesis
• Transjugular intrahepatic portosystemic shunt, peritoneovenous shunt

Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107.

Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky,
Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 2087-2106

• 1st line treatment
• Sodium restriction (~ 90 mEq/day = 2000 mg per day [88 mmol per day] = 5.2 g of dietary
salt/day1,2) = NO added salt diet with avoidance of pre-prepared meals
• Fluid restriction: NOT necessary (UNLESS serum sodium < 125 mmol/L)
• Urine Sodium Monitoring
• Random urinary sodium concentrations (lack of uniformity of sodium excretion during the
day and lack of knowledge of total urine volume)
• 24-hour collections of urine for determination of sodium excretion: >78 mEq/day
(cumbersome)
• Urine sodium/potassium ratio (“spot” urine): > 1 = enough to loss weight
DIET
1. Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107
2. Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 2087-2106
3. EASL (2010), J Hepatol, 53 (3), pp. 397-417

• Dose
• Single morning doses of oral spironolactone (100 mg) ± furosemide (40 mg)
• Increased simultaneously every 3-5 days (maintaining 100:40 mg ratio to maintains
normokalemia, >< hyperaldosteronism characteristic of most cirrhotis with ascites)
• Maximum doses: 400 mg per day of spironolactone, 160 mg per day of furosemide
• Amiloride: not produce gynecomastia  recommended in patients with intolerable painful
gynecomastia, but signifcantly less natriuretic eﬀect than spironolactone
• 20 to 60 mg/day
• Other diuretics (metolazone, thiazides, torsemide): NO evidence of advantage over
spironolactone and furosemide
DIURETICS (1)

Dancygier H. (2014), Mount Sinai Expert Guides - Hepatology, Jawad Ahmad, Scott L.
Friedman, Henryk Dancygier, Editors, Wiley Blackwell, pp. 209-226

• Complications
• Furosemide: can be temporarily withheld with hypokalemia (<3 mmol/L)1,2 (very common
in alcoholic hepatitis)
• Parenchymal renal disease (e.g., diabetic nephropathy or immunoglobulin A nephropathy)
or post liver transplantation: may tolerate less spironolactone than usual (because of
hyperkalemia)
• Painful gynecomastia (spironolactone  antiandrogenic activity)
• Renal impairment
• Hepatic encephalopathy
• Hyponatremia
DIURETICS (1)
1. EASL (2010), J Hepatol, 53 (3), pp. 397-417

• Temporarily withheld in setting of: active GI bleeding, hepatic encephalopathy, or renal
dysfunction
• Cessation of diuretics:
• Uncontrolled or recurrent encephalopathy
• OR Serum Na < 120 mmol/L despite fluid restriction
• OR Serum creatinine > 2.0 mg/dL (180 mol/L)
DIURETICS (3)

• Significant edema:
• NO limit to daily weight loss
• Usually 1 kg/day
• Edema has resolved: 0.5 kg is probably a reasonable daily maximum
WEIGHT LOSS

• ACEI, ARB: may be harmful, must be carefully considered in each patient, monitoring blood
pressure and renal function (BP/cirrhosis and ascites is supported by  vasoconstrictors
such as vasopressin, angiotensin, and aldosterone)
• NSAIDs: avoided in patients with cirrhosis and ascites, except in special circumstances
(reduce urinary sodium excretion in patients with cirrhosis and can induce azotemia)
• Aminoglycosides (increased risk of renal failure)  reserved for bacterial infections that
cannot be treated with other antibiotics
DRUG USE CAUTIOUS

• Tense ascites
• Post-paracentesis albumin infusion
• May not be necessary for a single paracentesis of < 4-5 L
• Large-volume paracenteses: 6-8 g albumin/liter of fluid removed* (appears to improve
survival)
• Complications of large therapeutic paracentesis (> 5L):
• Leakage, bleeding: most common
• Scrotal edema (subcutaneous tracking of peritoneal ﬂuid)
• Post-paracentesis circulatory dysfunction (PCD or PPCD): worsening of the vasodilatory
state, further  in eﬀective arterial blood volume, marked activation of neurohumoral systems
THERAPEUTIC PARACENTESIS
(*) Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107.

Garcia-Tsao G. (2018), Zakim and Boyer’s Hepatology: A
Textbook of Liver Disease, Arun J. Sanyal, et al., Editors, Elsevier,
pp. 220-232

• Controversial, impratical, no RCT
• NOT recommended for the treatment of patients with uncomplicated ascites
• Hypothesis: upright posture activates sympathetic nervous system and RAA system
(aggravate plasma renin elevation/cirrhosis and ascites)
BED REST

Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory
Fitz, Editors, Wiley Blackwell, pp. 2087-2106

REFRACTORY ASCITES (1)
• Definition:
• Treatment duration
• Lack of response
• Early ascites recurrence
• Diuretic-induced complications
• Presentation:
• Minimal to no weight loss together with inadequate urinary Na excretion despite diuretics
• Development of clinically significant complications of diuretics
• Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107
• Dancygier H. (2014), Mount Sinai Expert Guides - Hepatology, Jawad Ahmad, Scott L. Friedman, Henryk Dancygier, Editors, Wiley Blackwell, pp. 209-226

Moore K. P., Wong F., Gines P., et al. (2003), Hepatology, 38 (1), pp. 258-66

REFRACTORY ASCITES (2)
• Treatment:
• Oral midodrine
• Serial therapeutic paracenteses ± post-paracentesis albumin infusion: choice of option
• Liver transplantation
• TIPS: intolerant of repeated large volume paracentesis
• Peritoneovenous shunt: not candidates for paracenteses, transplant, or TIPS
• Careful attention to medications
• Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107
• Colombato L. (2007), J Clin Gastroenterol, 41 Suppl 3, pp. S344-51

Runyon B. A. (2012), Schiff’s Diseases of the Liver, Eugene R. Schiff, Willis C. Maddrey, Michael F. Sorrell, Editors, Wiley-Blackwell, pp. 393-420

• GI bleeding, hepatic encephalopathy, bacterial infection, hypotension, azotemia, and/or HCC
• For definitive diagnosis + management of liver disease & fluid overload
• Assessment of response of ascites to diuretic therapy and salt restriction: should only be
performed in stable patients without associated complications (e.g, bleeding or infection)
HOSPITALIZATION

Ascitic Fluid
Infection
PHUNG HUY HOANG, MD
September 2017

CLASSIFICATION
• Based on: ascitic culture results, PMN count, presence or absence of a surgical source
of infection
• Classification
• Spontaneous ascitic fluid infection
• Spontaneous bacterial peritonitis (SBP)
• Monomicrobial nonneutrocytic bacterascites (MNB)
• Culture-negative neutrocytic ascites (CNNA)
• Secondary bacterial peritonitis
• Gut perforation
• Nonperforation
• Polymicrobial bacterascites

DEFINITION (1)
SPONTANEOUS BACTERIAL PERITONITIS
•  ascitic fluid absolute PMN count (i.e., > 250 cells/mm3 [0.25 x109/L])
• Without an evident intra-abdominal, surgically treatable source of infection
MONOMICROBIAL NONNEUTROCYTIC BACTERASCITES
• Positive ascitic fluid culture (bacterascites) for a single organism
• Ascitic fluid PMN count < 250/mm3 (0.25 × 109/L)
• No evidence of an intraabdominal surgically treatable source of infection
POLYMICROBIAL BACTERASCITES
• Multiple organisms on Gram stain or cultured from the ascitic fluid
• PMN count < 250/mm3 (0.25 × 109/L)

DEFINITION (2)
CULTURE-NEGATIVE NEUTROCYTIC ASCITES
• Ascitic fluid culture grows no bacteria
• Ascitic fluid PMN count ≥ 250/mm3 (0.25 × 109/L)
• No antibiotics given (not even a single dose)
• No other explanation for an elevated ascitic PMN count (e.g., hemorrhage into ascites,
peritoneal carcinomatosis, TB, or pancreatitis) can be identifed
SECONDARY BACTERIAL PERITONITIS
• Ascitic fluid culture positive (usually for multiple organisms)
• PMN count ≥ 250/mm3 (0.25 × 109/L)
• An intra-abdominal surgically treatable primary source of infection (e.g., perforated
intestine, perinephric abscess) has been identifed

CLINICAL SETTING (1)
• Spontaneous variants of ascitic ﬂuid infection (SBP, CNNA, MNB): occur almost
exclusively in the setting of severe liver disease
• Chronic (cirrhosis)
• Acute (fulminant hepatic failure) or subacute (alcoholic hepatitis)
• SBP/cirrhosis
• Ascites: prerequisite for development of SBP
• Peritonitis: unlikely to precede development of ascites
• Secondary bacterial peritonitis, polymicrobial bacterascites: can develop with ascites of
any type

CLINICAL SETTING (2)
• MNNB: probably represents an early stage of ascitic ﬂuid infection
• Polymicrobial bacterascites: needle entry of the bowel during attempted paracentesis
(paracentesis is traumatic, unusually difficult because of ileus, when stool or air is aspirated
into the paracentesis syringe)
• CNNA
• Previous antibiotic treatment (even 1 dose)
• Inadequate volume of ﬂuid inoculated
• Spontaneously resolving SBP (paracentesis performed after all bacteria have been
killed by host defenses but before the PMN count has normalized)

PATHOGENESIS OF SBP
• Overgrowth of a specifc organism in the intestine
• Translocation of that microbe from the intestine to mesenteric lymph nodes
• Spontaneous bacteremia and subsequent colonization of susceptible ascitic fluid
• Ascitic fluid protein concentration:
• NOT change with development of spontaneous infection
• LOW-protein ascitic fluid (< 1 g/dL or < 1.5 g/dL): particularly susceptible to SBP (opsonic
activity, correlate ascites complement levels)
• SBP: worsens hyperdynamic circulatory state (cytokine-mediated increase in vasodilatation)
 renal dysfunction, hepatorenal syndrome

Runyon B. A. (2012), Schiff’s Diseases of the Liver, Eugene R. Schiff, Willis
C. Maddrey, Michael F. Sorrell, Editors, Wiley-Blackwell, pp. 393-420

RISK FACTORS
• Cirrhosis: a form of acquired immunodefciency (in the generic sense)  impaired local and
systemic immune defenses
• Low ascitic ﬂuid total protein concentrations, as well as the phagocytic (both motile and
stationary) dysfunction
• Paracentesis ±
• GI hemorrhage (peak 48 hours after the onset of hemorrhage; shock-induced increase in the
translocation of bacteria from the intestine to extraintestinal sites)
• Urinary tract infections

BACTERIOLOGY
• SPB, MNB: Escherichia coli, streptococci (mostly pneumococci), Klebsiella
• Antibiotic susceptibility of bacteria/cirrhosis should be tested periodically in each hospital
 preferred empirical antibiotic regimens
• Spontaneous forms: always monomicrobial >< secondary forms (secondary peritonitis,
polymicrobial bacterascites): usually are polymicrobial (frequently including fungi and
enterococcus)

DIAGNOSIS (1)
• Fever or abdominal pain, unexplained mental change, aundice, worsening renal
failure, acidosis, peripheral leukocytosis/patient with ascites
• A ‘‘clinical diagnosis’’ of infected ascitic fluid without a paracentesis: NOT adequate;
clinician’s clinical impression that infection is unlikely: NOT rule out infection
• High index of suspicion and a low threshold for performing a paracentesis
• Secondary peritonitis should be considered in any patient with neutrocytic ascites
• Clinical symptoms and signs: NOT distinguish patients with secondary peritonitis from
those with SBP (peritoneal signs: require contact of inﬂamed visceral and parietal
peritoneal surfaces  not occur when large volume of ﬂuid separating these surfaces)
• Simultaneous blood and urine cultures and a chest radiograph

DIAGNOSIS (2)
• Isolation of bacteria from fluid samples will be maximized by:
1. Fluid is cultured in blood culture bottles
2. No prior antibiotic treatment
3. No other explanation for an elevated PMN count (e.g., hemorrhagic ascites, peritoneal
carcinomatosis, pancreatitis, or peritoneal tuberculosis)

PARACENTESIS/SECONDARY PERITONITIS (1)
• Brown ascitic ﬂuid + bilirubin > 6 mg/dL (102 µmol/L) & > serum level: biliary or proximal
small intestinal perforation
• Ascitic ﬂuid amylase level > 5-fold of serum level: intestinal rupture (but not gallbladder rupture)
• Measurement of ascitic fluid total protein, glucose, and LDH has been reported to be of value
in distinguishing SBP from secondary peritonitis (gut perforation into ascites)
• An ascitic fluid carcinoembryonic antigen > 5 ng/mL, or ascitic fluid ALP > 240 units/L*
• Suggesting gut perforation into ascitic fluid (Sens 92%, Spec of 88%)
• Would NOT be predicted to be useful in nonperforation secondary peritonitis
• Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107.
• (*) Wu S. S., Lin O. S., Chen Y. Y., et al. (2001), J Hepatol, 34 (2), pp. 215-21

PARACENTESIS/SECONDARY PERITONITIS(2)
• Neutrocytic ascitic fluid + 2/3 following criteria = likely to have surgical peritonitis:
1. Total protein >1 g/dL,
2. Glucose <50 mg/dL,
3. LDH > the upper limit of normal for serum (225 U/L)
• These criteria and/or polymicrobial infection: 96% sensitive/detecting secondary bacterial
peritonitis
• Akriviadis E. A., Runyon B. A. (1990), Gastroenterology, 98 (1), pp. 127-33
• Soriano G., Castellote J., Alvarez C., et al. (2010), J Hepatol, 52 (1), pp. 39-44

TREATMENT
• Antibiotics empirical treatment
• Indications1,2:
• Ascitic fluid PMN counts ≥ 250 cells/mm3 + clinical setting compatible with ascitic
fluid infection
• Ascitic fluid PMN < 250 cells/mm3 + signs or symptoms of infection
• ± MNB (discontinued after only 2–3 days if culture remains negative and suspicion of
infection has diminished)
• Duration:
• 5–7 days, or guided by the course of ascites PMNs1
• 10-14 days for life-threatening infections3
1. Runyon B. A. (2012), Hepatology, 49 (6), pp. 2087-2107
2. Garcia-Tsao G. (2016), Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 2087-2106.
3. Runyon B. A. (2016), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 1553-1576

TREATMENT
• Antibiotics empirical treatment
• Choice of antibiotics
• Community-acquired:
• 3rd-cephalosporin: cefotaxime 2g IV q8h, ceftriaxone 2g IV q24h, ceftazidime 1g
IV q12–24h
• Quinolone: WITHOUT prior exposure to quinolones, vomiting, shock, grade II (or
higher) HE, or serum creatinine > 3 mg/dL
• Nofloxacin 400mg PO bid
• OR ciprofloxacin, ofloxacin
• Nosocomial or healthcare associated infections: broader spectrum antibiotics
(e.g., vancomycin/tazobactam, imipenem, ertapenem)
• Results of susceptibility testing  antibiotic with a narrower spectrum of activity
1. EASL (2010), J Hepatol, 53 (3), pp. 397-417

TREATMENT
• Albumin transfusion:
• Indication: ascitic fluid PMN counts ≥ 250 cells/mm3 + clinical suspicion of SBP +
serum creatinine >1 mg/dL, BUN >30 mg/dL, or total bilirubin >4 mg/dL
• Dose: 1.5 g/kg within 6 hours of detection  1.0 g/kg on day 3 (maximum 100 g/day)
• Decreased risk of renal failure (renal dysfunction: main predictor of death in SBP*):
bacterial infection further increases vasodilatation
• Secondary peritonitis:
• Urgent surgical management
• Broader spectrum empirical antibiotic coverage than those with SBP: cefotaxime plus
metronidazole
• (*) Tandon P., Garcia–Tsao G. (2011), Clinical Gastroenterology and Hepatology, 9 (3), pp. 260-265.

FOLLOW-UP PARACENTESIS
• Assess response in PMN count and culture
• Improvement of SBP: >25%  of ascitic ﬂuid PMN count1
• Therapy failure:  in ascites PMN count < 25%  investigations to rule out secondary
peritonitis + broadening antibiotic coverage spectrum (include MDR organisms)
• Not routinely
• Indication2:
• Nosocomial setting
• Recent β-lactam antibiotic exposure
• Culture an atypical organism(s)
• Atypical clinical response to treatment
1. Rimola A., García-Tsao G., Navasa M., et al. (2000), Journal of Hepatology, 32 (1), pp. 142-153

PREVENTION
PRIMARY
• GI bleeding:
• IV ceftriaxone for 7 days (1g/day), OR norfloxacin (PO 400mg b.i.d) for 7 days
• To prevent bacterial infections/cirrhosis
• Cirrhosis and ascites:
• Long-term use of norfloxacin (400mg/day), or TMP/SMZ (800/160mg daily)
• Indication: ascitic fluid protein <1.5 g/dL + impaired renal function (creatinine >1.2, BUN
>25 or serum Na <130) or liver failure (Child score >9 and bilirubin >3)
1. EASL (2010), J Hepatol, 53 (3), pp. 397-417

PREVENTION
SECONDARY
• Long-term prophylaxis with norfloxacin (400mg daily, PO), ciprofloxacin (500 mg b.i.d, or 750
mg once weekly, PO) or TMP/SMZ (800/160mg daily, PO)
• Duration: until disappearance of ascites, death, or transplant
• Long-term secondary prophylaxis will result in
• Change of bacterial spectrum towards Gram (+) cocci
• Emergence of quinolone resistant Gram-negative organisms
1. EASL (2010), J Hepatol, 53 (3), pp. 397-417

Hepatic
hydrothorax
PHUNG HUY HOANG, MD
September 2017

• Large pleural effusion (usually unilateral and right-sided) in patient with cirrhosis and ascites
• Location: right-sided in 80%, left-sided (can be due to tuberculosis, cancer, or
pancreatitis) in 18%, bilateral in 3%1
• Ascites may occasionally not be clinically obvious
• 5-6% of patients with cirrhosis and ascites1,2
• Transdiaphragmatic movement of ﬂuid from the peritoneal to the pleural space through
small diaphragmatic defects (negative intrathoracic pressure)
1. Krok K. L., Cardenas A. (2012), Semin Respir Crit Care Med, 33 (1), pp. 3-10
2. Strauss R. M., Boyer T. D. (1997), Semin Liver Dis, 17 (3), pp. 227-32
INTRODUCTION

• Fluid resembles ascites
• Transudative in nature, SPAG > 1.1
• Protein concentration/pleural fluid usually > ascitic fluid  differences in the hydrostatic
forces in the abdomen versus the chest)
• Radionuclide ascites scan: in cases where ascites is absent (injection of Tc-99m-labelled
sulfur colloid or macroaggregated serum albumin into the peritoneal cavity followed by chest
imaging every 15–30 min)
• EASL (2010), J Hepatol, 53 (3), pp. 397-417
• Runyon B. A. (2012), Schiff’s Diseases of the Liver, Eugene R. Schiff, Willis C. Maddrey, Michael F. Sorrell, Editors, Wiley-Blackwell, pp. 393-420
DIAGNOSIS

Krok K. L., Cardenas A. (2012), Semin Respir Crit Care Med, 33 (1), pp. 3-10

• Spontaneous bacterial pleural empyema (SBEM)
• Source: SBP and transmission of bacteria across diaphragm
• Diagnostic thoracocentesis should be performed in patients with pleural effusion and
suspected infection with inoculation of fluid into blood culture bottles
• Diagnosis:
• Positive pleural fluid culture and increased neutrophil count of >250/mm3
• OR negative pleural fluid culture and >500 neutrophils/mm3 in the absence of
pneumonia
• EASL (2010), J Hepatol, 53 (3), pp. 397-417
• Runyon B. A. (2012), Schiff’s Diseases of the Liver, Eugene R. Schiff, Willis C. Maddrey, Michael F. Sorrell, Editors, Wiley-Blackwell, pp. 393-420
DIAGNOSIS

• Management: same manner as cirrhotic ascites
• Placement of a chest tube: contraindicated (multiple complications, mainly volume and
electrolyte disturbances)
• Surgical repair of diaphragm defects
• EASL (2010), J Hepatol, 53 (3), pp. 397-417
TREATMENT

1. Akriviadis E. A., Runyon B. A. (1990), "Utility of an algorithm in differentiating spontaneous from secondary bacterial
peritonitis", Gastroenterology, 98 (1), pp. 127-33.
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hypertension", J Clin Gastroenterol, 41 Suppl 3, pp. S344-51.
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Editors, Wiley Blackwell, pp. 209-226.
11. Dancygier H. (2014), "Spontaneous Bacterial Peritonitis", Mount Sinai Expert Guides - Hepatology, Jawad Ahmad, Scott L.
Friedman, Henryk Dancygier, Editors, Wiley Blackwell, pp. 227-234.
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13. Epstein O., Perkin G. D., Cookson J., et al. (2009), "The abdomen", Pocket Guide to Clinical Examination, Mosby Elsevier, pp.
139-168.
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Sanyal, et al., Editors, Elsevier, pp. 220-232.
15. Garcia-Tsao G. (2016), "Ascites and its complications", Yamada’s Textbook of Gastroenterology, Daniel K. Podolsky, Michael
Camilleri, J. Gregory Fitz, Editors, Wiley Blackwell, pp. 2087-2106.
16. Hillebrand D. J., Runyon B. A., Yasmineh W. G., et al. (1996), "Ascitic fluid adenosine deaminase insensitivity in detecting
tuberculous peritonitis in the United States", Hepatology, 24 (6), pp. 1408-12.
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with chronic liver disease", J Lab Clin Med, 102 (2), pp. 260-73.
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19. MacGilchrist A., Iredale J., Parks R. (2013), "The gastrointestinal system", Macleod’s Clinical Examination, Graham Douglas,
Fiona Nicol, Colin Robertson, Editors, Churchill Livinstone, pp. 165-194.
20. Moore K. P., Wong F., Gines P., et al. (2003), "The management of ascites in cirrhosis: report on the consensus conference of the
International Ascites Club", Hepatology, 38 (1), pp. 258-66.
21. Rimola A., García-Tsao G., Navasa M., et al. (2000), "Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis:
a consensus document", Journal of Hepatology, 32 (1), pp. 142-153.
22. Riquelme A., Calvo M., Salech F., et al. (2006), "Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of
tuberculous peritonitis: a meta-analysis", J Clin Gastroenterol, 40 (8), pp. 705-10.
23. Runyon B. A. (2016), "Ascites and Spontaneous Bacterial Peritonitis", Sleisenger and Fordtran’s Gastrointestinal and Liver Disease,
Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Editors, Elsevier Saunders, pp. 1553-1576.
24. Runyon B. A. (2012), "Ascites and Spontaneous Bacterial Peritonitis", Schiff’s Diseases of the Liver, Eugene R. Schiff, Willis C.
Maddrey, Michael F. Sorrell, Editors, Wiley-Blackwell, pp. 393-420.

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2107.
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(5), pp. 1351-5.
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Hepatology, 5 (2), pp. 257-9.
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transudate concept in the differential diagnosis of ascites", Ann Intern Med, 117 (3), pp. 215-20.
30. Soriano G., Castellote J., Alvarez C., et al. (2010), "Secondary bacterial peritonitis in cirrhosis: a retrospective study of clinical
and analytical characteristics, diagnosis and management", J Hepatol, 52 (1), pp. 39-44.
31. Strauss R. M., Boyer T. D. (1997), "Hepatic hydrothorax", Semin Liver Dis, 17 (3), pp. 227-32.
32. Tandon P., Garcia–Tsao G. (2011), "Renal Dysfunction Is the Most Important Independent Predictor of Mortality in Cirrhotic
Patients With Spontaneous Bacterial Peritonitis", Clinical Gastroenterology and Hepatology, 9 (3), pp. 260-265.
33. Wu S. S., Lin O. S., Chen Y. Y., et al. (2001), "Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the
differentiation of primary from secondary bacterial peritonitis with intestinal perforation", J Hepatol, 34 (2), pp. 215-21.

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