Ascites and Spontaneous Bacterial Peritonitis

Question 1

PATHOGENESIS OF ASCITES IN CIRRHOSIS

Answer 1

The key mechanism leading to the formation of ascites in patients with cirrhosis is renal sodium retention due to activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS).

Question 2

The most common functional renal abnormalities in patients with cirrhosis

Answer 2

impaired ability to excrete sodium, an impaired ability to excrete solute-free water, and a reduction in the glomerular filtration rate (GFR) secondary to renal vasoconstriction.

sodium retention is associated with extracellular fluid volume expansion.

Question 3

portal Hypertension

Answer 3

represents the triggering factor for the development of circulatory dysfunction in patients with advanced cirrhosis.

Nitric oxide (NO) has been shown to be a key regulator of intrahepatic vascular tone

Finally, intrahepatic inflammation has also been described to play a role in the increased vascular resistance leading to portal hypertension..

Question 4

In advanced cirrhosis,

Answer 4

Kupffer cells have been involved in the development of hepatic inflammation and oxidative stress, leading to increased intrahepatic vascular resistance.

Question 5

portal hypertension is assessed by

Answer 5

the measurement of the hepatic venous pressure gradient (HVPG), defined
as the difference between wedged and free hepatic venous pressure,
measured by hepatic vein catheterization

Question 6

The Renin-Angiotensin-Aldosterone System

Answer 6

Plasma aldosterone levels are increased in most cirrhotic patients with ascites and marked sodium retention.
The important role of aldosterone in the pathogenesis of sodium retention and ascites is supported by data showing that there is an inverse correlation between urinary sodium excretion and plasma aldosterone levels.

administration of spironolactone, a specific aldosterone antagonist, is able to reverse sodium retention in the great majority of patients with ascites without renal failure

Question 7

the administration of angiotensin II receptor antagonists or converting-enzyme inhibitors to cirrhotic patients with ascites

Answer 7

increased PRA induces a marked reduction in arterial pressure and systemic vascular resistance, thereby
suggesting that the activation of RAAS is a homeostatic response to maintain arterial pressure in these patients

Question 8

According to the International Club of Ascites, ascites is classified

Answer 8

ascites is classified based on quantitative parameters.
Grade 1 ascites is defined as mild ascites that is detectable only by US;
grade 2 ascites is defined as moderate ascites detectable by physical examination; and
grade 3 ascites is defined as large ascites with marked abdominal distention.

Question 9

recurrent ascites

Answer 9

Ascites that recurs at least 3 times within a one-year period, despite appropriate treatment

Question 10

Assessment of Renal Sodium Excretion

Answer 10

Ideally, urine should be collected under conditions of controlled sodium intake (a low-sodium diet of approximately 90 mEq/day during the previous 5 to 7 days), because sodium intake may influence sodium excretion.

Although the measurement of sodium concentration on a “spot” analysis of urine provides an estimate of sodium excretion, the assessment of sodium excretion in a 24-hour period is preferable because it is more representative of sodium excretion throughout the day.

Sodium excretion should be measured without diuretic therapy in patients with a first episode of ascites or with worsening of pre-existing ascites (e.g., a marked increase in ascites despite treatment).

Question 11

Patients with moderate sodium retention

Answer 11

(urine sodium ≥10 mEq/day) are more likely to respond to lower doses of diuretic treatment than those with marked sodium retention.

Question 12

An ascitic neutrophil count higher than 250/mm3 is

Answer 12

diagnostic of SBP

Question 13

ascitic fluid protein less than 1.5 g/dL is also

Answer 13

associated with an increased risk of developing SBP

Question 14

HIGH GRADIENT ≥1.1 g/dl (11 g/L)

Answer 14

Alcohol-associated hepatitis
ALF
Budd-Chiari syndrome
Cardiac ascites
Cirrhosis
Fatty liver of pregnancy
Massive liver metastases “Mixed” ascites
Myxedema
Portal vein thrombosis Sinusoidal obstruction syndrome

Question 15

LOW GRADIENT <1.1 g/dL (11 g/L)

Answer 15

Biliary ascites
Bowel obstruction or infarction Nephrotic syndrome
Pancreatic ascites
Peritoneal carcinomatosis Postoperative lymphatic leak
Serositis in connective tissue diseases Tuberculous peritonitis

Question 16

a sensitive and specific measurement to determine whether ascites is related to portal hypertension

Answer 16

The serum-ascites albumin gradient (SAAG)

Question 17

If the SAAG is 1.1 g/dL (11 g/L) or greater, the patient.

Answer 17

can be considered to have portal hypertension with an accuracy of approximately 97%.

Question 18

By contrast, if the SAAG is less than 1.1 g/ dL (11 g/L),

Answer 18

the patient is unlikely to have portal hypertension

Question 19

The SAAG

Answer 19

does not confirm the diagnosis of the cause of ascites but is an indirect and accurate index of portal hypertension.

Question 20

If ascitic fluid is infected and secondary bacterial peritonitis rather than SBP is

Answer 20

suspected, the measurement of glucose, amylase, lipase, and LDH in ascitic fluid may be useful.

Question 21

in the setting of secondary bacterial peritonitis,

Answer 21

glucose levels are markedly low and close to 0 mg/dL due to significantly increased numbers of leukocytes and bacteria in ascites.

Question 22

cardiac ascites is

Answer 22

characterized by a high ascitic protein concentration (≥2.5 g/dL) despite a SAAG of 1.1 g/dL or greater.

Question 23

Cytology of the ascitic fluid

Answer 23

is specific but rather insensitive for detection of malignant cells, which are formed in only 40% to 70% of patients with malignant ascites.

Question 24

abdominal tuberculosis, the ascitic fluid will have a high protein concentration

Answer 24

Adenosine deaminase may also be measured in ascitic fluid, with high levels observed in patients with tuberculosis; however, its sensitivity has been shown to be low, particularly in patients with cirrhosis.

Question 25

Chylous ascites

results from rupture of intra-abdominal lymphatic vessels.

Answer 25

is the term used to describe ascitic fluid that has a milky appearance caused by triglyceride levels greater than 200
mg/dL and usually greater than 1000 mg/dL

Cirrhosis is the most common cause of chylous ascites, and the high
lymphatic flow and increased pressure due to splanchnic arterial
vasodilatation are presumed to be the reasons for its development. .

Question 26

Hepatic hydrothorax

Answer 26

is defined as the accumulation of fluid in the pleural space of patients with decompensated cirrhosis and ascites, in the absence of pulmonary, cardiac, or pleural disease.

develops because of small diaphragmatic defects that allow the passage of ascites to the pleural space due to the negative thoracic pressure induced by inspiration.

Question 27

Typically, pleural fluid in patients with hepatic hydrothorax

Answer 27

has a low protein concentration.

Question 28

Uncomplicated Ascites

Answer 28

Treatment of ascites is aimed at achieving a negative sodium balance and, therefore, is based on reducing sodium intake together with increasing renal sodium excretion with diuretic treatment.

Question 29

Grade 1 Ascites

Answer 29

recommend no treatment

Question 30

Grade 2 Ascites

Answer 30

Patients with grade 2 ascites show moderate renal sodium retention, with baseline urine sodium excretion greater than 20 mEq/L in most cases.

A negative sodium balance with loss of ascites can be easily obtained in most cases by reducing dietary sodium intake and increasing renal sodium excretion with diuretics

dietary sodium intake should be moderately restricted to 80 to 120 mEq/day, which corresponds to approximately 4.6 to 6.9 g of salt per day and is generally equivalent to a “no-added salt” diet with the avoidance of preprepared meals.

Question 31

Because hyperaldosteronism plays a key role in renal sodium retention in cirrhosis,

Answer 31

anti-mineralocorticoids (particularly spironolactone or eplerenone) represent the first line of treatment in the management of cirrhotic ascites.

Anti-mineralocorticoids have a slow mechanism of action, and the dose of these diuretics should not be increased sooner than 72 hours after the previous change in dose.

Question 32

in view of these results, guidelines recommend that patients with a first episode of ascites should be treated initially

Answer 32

with anti-mineralocorticoids alone (i.e., spironolactone 100 mg/day), because they will likely show a positive response with a low rate of side effects.

Question 33

In case of a lack of response, the dose of the drug should be increased

Answer 33

by 100 mg no less than every 72 hours to a maximum of 400 mg/day.

Question 34

In patients who do not respond to treatment, defined as a reduction in body weight below 2 kg/week or in those in whom hyperkalemia develops,

Answer 34

furosemide should be added to the regimen at an initial dose of 40 mg/day, with sequential 40-mg increases to a final dose of 160 mg/day, as needed

Question 35

The best approach for patients with recurrent ascites

Answer 35

is combined diuretic treatment with an anti-mineralocorticoid and loop diuretic, with increases in doses in a stepwise manner according to the response

Question 36

the diuretic dose should be titrated to

Answer 36

achieve a weight loss of less than or equal to 0.5 kg/ day in patients without peripheral edema and up to 1 kg/day in patients with ascites and edema.

Question 37

Management of Grade 2 (Moderate) Ascites

Answer 37

DIET
Low-sodium diet (80-120 mEq/day)

DIURETICS
First episode of ascites:
Spironolactone, 100 mg/day; increase in a stepwise manner every 72 hr according to treatment response to a maximum dose 400 mg/day
If no response or hyperkalemia develops, add furosemide, 40 mg/ day, increasing in a stepwise manner to a maximum dose of 160 mg/day
Recurrent ascites:
Combination diuretic treatment with spironolactone and furosemide (same doses as above)

MONITORING
Daily body weight (recommended body weight loss is up to 0.5 kg/
day in patients without edema and 0.5-1 kg/day in patients with
ascites and edema)
Once ascites has been mobilized, continue a low-sodium diet and
the minimum diuretic dose necessary to avoid reaccumulation of ascites

Question 38

Management of Grade 3 (Tense) Ascites

Answer 38

DIET
Low-sodium diet (80-120 mEq/day)

LARGE-VOLUME PARACENTESIS
IV albumin should be administered (8 g per L of ascites removed)

DIURETICS
The minimum diuretic dose necessary to avoid accumulation of
ascites should be continued
If the patient has not received diuretic treatment previously, start
with spironolactone, 100 mg/day, and furosemide, 40 mg/day If the patient was receiving diuretic treatment, restart diuretics at
a higher dose. If there is no response to treatment, assess the patient’s sodium intake for adherence to a low-sodium diet, and increase the diuretic doses progressively to a maximum of spironolactone, 400 mg/day, and furosemide, 160 mg/day

Question 39

Diagnostic Criteria of Refractory Ascites

Answer 39

DIURETIC-RESISTANT ASCITES
DIURETIC-INTRACTABLE ASCITES
PRIOR TREATMENT

Question 40

DIURETIC-RESISTANT ASCITES

Answer 40

Ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of a lack of response to sodium restriction and diuretic treatment

Question 41

DIURETIC-INTRACTABLE ASCITES

Answer 41

Ascites that cannot be mobilized or the early recurrence of which cannot be prevented because of the development of diuretic- induced complications that preclude the use of an effective diuretic dosage

Question 42

PRIOR TREATMENT

Answer 42

Patients must be on an intensive diuretic therapy (spironolactone 400 mg/day and furosemide 160 mg/day) for at least 1 wk and on a salt-restricted diet of <80 mEq/day

Question 43

Lack of response:

Answer 43

mean weight loss of <0.8 kg over 4 days and urinary sodium output less than sodium intake

Question 44

Early ascites recurrence:

Answer 44

reappearance of grade 2 or 3 ascites within 4 wk of initial mobilization

Question 45

Diuretic-induced hepatic encephalopathy:

Answer 45

the development of encephalopathy in the absence of any other precipitating factor

Question 46

Diuretic-induced renal impairment:

Answer 46

an increase of the serum creatinine level by >100% to a value >2 mg/dL in a patient with ascites that is responding to treatment

Question 47

Midodrine

Answer 47

is an α1-adrenergic agonist that has been shown to improve circulatory and kidney function in patients with cirrhosis and ascites

Question 48

midodrine and albumin,

Answer 48

administration of albumin is still not recommended as a long-term treatment for the management of all patients with decompensated cirrhosis and ascites.

Question 49

SPONTANEOUS BACTERIAL PERITONITIS

Answer 49

Bacterial infections are a common complication in patients with cirrhosis and are associated with the development of other cirrhosis-related complications (e.g., AKI, hepatic encephalopathy) and a poor prognosis.

Together with urinary tract infections,
SBP represents the most common type of infection in patients
with cirrhosis, followed by pneumonia, soft tissue infections,
and spontaneous bacteremia.

Question 50

SBP can present with local symptoms, such as abdominal pain, vomiting, or diarrhea, and can also present without local symptoms and with the following:

Answer 50

(1) signs of systemic inflammation (i.e., fever, high leukocyte count, high serum C-reactive protein level, tachycardia); (2) deterioration of liver function; (3) hepatic encephalopathy; (4) AKI; or (5) septic shock.

Question 51

Alterations in the Gut-Liver Axis

Answer 51

Cirrhosis is characterized by alterations at different levels of the
gut-liver axis that result in pathologic bacterial translocation
and spillover of endotoxins into the systemic circulation, thus
facilitating the development of bacterial infections.

Question 52

ACLF(acute-chronic liver failure) is a syndrome

Answer 52

characterized by acute
decompensation of cirrhosis associated with one or more organ
failures;

bacterial infections have been described to be the main triggers of ACLF

Question 53

a low ascitic- fluid protein concentration (<1.0 to 1.5 g/dL)

Answer 53

has been associated with an increase in the risk of SBP

Question 54

The cutoff value with the best sensitivity for the diagnosis of SBP

Answer 54

is an ascitic neutrophil count of 250/mm3.

Question 55

patients may present with a positive ascitic fluid culture result but an ascitic neutrophil count below 250/ mm3.
This condition is known as

Answer 55

bacterascites.

Question 56

For community-acquired infections, the most common bacteria that cause SBP are Gram-negative organisms.

Answer 56

Therefore, the empirical antibiotic treatment of choice for patients with community-acquired SBP has classically been a third-generation cephalosporin.

Question 57

marked increase in infections caused by MDR bacteria,

Answer 57

defined as bacteria with acquired non-susceptibility to at least 1 agent in 3 or more antimicrobial categories,

Question 58

____ has been recommended as the first-line treatment in patients with health care-associated or nosocomial SBP in areas with a low prevalence of MDR bacteria.

Answer 58

piperacillin/tazobactam has been recommended as the first-line treatment in patients with health care-associated or nosocomial SBP in areas with a low prevalence of MDR bacteria.

Question 59

patients with severe health care-associated or nosocomial SBP— that is, those who fulfill criteria for sepsis, or in areas with a high prevalence of MDR bacteria—the recommended empirical antibiotic treatment

Answer 59

is meropenem alone or in combination with vancomycin or daptomycin, or linezolid

Question 60

Prophylaxis of SBP

Answer 60

Primary: norfloxacin, 400 mg/day or ciprofloxacin 500 mg/day or trimethoprim-sulfamethoxazole, 1 double-strength tablet a day

Criteria:
Cirrhosis with ascites
Ascitic fluid protein <1.5 g/dL
Child Pugh score ≥9, serum bilirubin level ≥3 mg/dL, serum creatinine level ≥1.2 mg/dL, and/or hyponatremia <130 mEq/L

Question 61

Prophylaxis of SBP

Answer 61

Secondary: norfloxacin, 400 mg/day or trimethoprim-sulfamethox-
azole, 1 double-strength tablet daily
Criteria: all patients with a previous episode of SBP