How to manage a cirrhotic patient with leukocytosis (elevated white blood cell count) and no evidence of infection?

Management of Leukocytosis in Cirrhotic Patients Without Evidence of Infection

Despite the absence of obvious infection, you must maintain an extremely high index of suspicion and perform a comprehensive diagnostic workup immediately, as cirrhotic patients frequently have occult infections that present atypically and carry significant mortality risk. 1

Understanding the Diagnostic Challenge

Leukocytosis in cirrhosis is particularly challenging because:

• Alcohol-associated hepatitis increases WBC count and other markers of systemic inflammation independent of infection, making it difficult to distinguish true infection from inflammatory states 1
• Fever is often absent in cirrhotic patients with sepsis, removing a key clinical indicator 1
• Biomarkers such as C-reactive protein, procalcitonin, lactate, and bacterial DNA are often elevated in cirrhosis both with and without infection, though persistent elevation is a poor prognostic indicator 1
• Up to one-third of patients with spontaneous infections may be entirely asymptomatic or present only with encephalopathy and/or acute kidney injury 2

Immediate Diagnostic Workup Algorithm

Step 1: Mandatory Diagnostic Paracentesis

Perform diagnostic paracentesis immediately in all cirrhotic patients with ascites and leukocytosis, regardless of symptoms 3, 4, 2:

• This is mandatory even without fever, abdominal pain, or other classic signs of infection 1, 3
• Inoculate at least 10 mL of ascitic fluid into blood culture bottles at the bedside before any antibiotics to increase culture sensitivity to >90% 3, 4
• Send ascitic fluid for cell count with differential, culture, and biochemical analysis 4
• Spontaneous bacterial peritonitis (SBP) is diagnosed when ascitic fluid PMN count is >250 cells/mm³, even with negative cultures 1, 3

Step 2: Comprehensive Infection Workup

Simultaneously obtain 4, 2:

• Blood cultures (obtained at the same time as paracentesis to increase organism isolation) 4, 2
• Urinalysis and urine culture (urinary tract infections account for 22% of infections in cirrhosis) 4, 2
• Chest X-ray (pneumonia accounts for 19% of infections) 4, 2
• Skin examination for soft tissue infections (8% of infections) 4, 2
• Complete blood count with differential 2

Step 3: Consider Additional Sources

• If pleural effusion is present, perform diagnostic thoracentesis to rule out spontaneous bacterial empyema, which can occur with or without SBP 4, 5

Critical Clinical Context

When Infection is Particularly Likely

A relative increase in WBC count, worsening mental status, hyponatremia, AKI, or hemodynamic changes frequently result from infection acquisition 1:

• These signs of new or worsening decompensation should trigger immediate empiric antibiotics while awaiting culture results 1
• Patients with alcoholic hepatitis may have fever, leukocytosis, and abdominal pain mimicking SBP, but an elevated PMN count must still be presumed to represent infection 1, 3

Special Consideration for Alcoholic Hepatitis

• In alcoholic hepatitis patients with fever and/or peripheral leukocytosis, empiric antibiotic treatment can be discontinued after 48 hours if ascitic fluid, blood, and urine cultures demonstrate no bacterial growth 1, 3
• These patients do not develop false-positive elevated ascitic fluid PMN counts because of peripheral leukocytosis 1

Management Based on Findings

If SBP is Confirmed (PMN >250 cells/mm³)

• Initiate third-generation cephalosporin immediately (cefotaxime 2g IV every 8 hours or ceftriaxone) 1, 4
• Administer albumin 1.5 g/kg at diagnosis and 1 g/kg on day 3 if there are signs of renal impairment to reduce hepatorenal syndrome risk 4
• Avoid aminoglycosides due to high nephrotoxicity risk 4

If Initial Workup is Negative

Continue close monitoring with serial assessments because:

• Bacterial infections occur 4-5 times more frequently in cirrhotic patients and account for one-third to one-half of deaths 3
• Infection should be suspected in any cirrhotic patient with unexpected deterioration of clinical course 6
• Consider repeat paracentesis if clinical status changes or leukocytosis persists 1, 3

Critical Pitfalls to Avoid

• Do not wait for fever or classic symptoms before investigating for infection - they are frequently absent 1
• Do not assume leukocytosis is solely from alcoholic hepatitis without ruling out infection - both can coexist 1
• Do not delay paracentesis - it is the only reliable way to diagnose or exclude SBP 1, 3, 4
• Do not rely solely on biomarkers (CRP, procalcitonin, lactate) as they lack specificity in cirrhosis 1
• Avoid unnecessary prolonged antibiotic use if cultures remain negative, as this increases risk of multidrug-resistant organisms 7

Prognostic Implications

• Patients with ACLF and infection have more severe systemic inflammation and higher probability of death than those with ACLF without infection 1
• 45% of cirrhotic patients discharged after successful treatment of one infection acquire another infection within 6 months 1
• The mortality of infections in cirrhosis is more than 20 times higher than the background population 6