In a middle‑aged adult with non‑alcoholic fatty liver disease, metabolic syndrome, intermittent chest pain, blurred vision, and anxiety‑like symptoms, what is the significance of a mild neutrophilic leukocytosis (white‑blood‑cell count 13 × 10⁹/L, absolute neutrophil count 8,476/µL) and how should it be evaluated?

Mild Neutrophilic Leukocytosis in NAFLD with Metabolic Syndrome

This mild neutrophilic leukocytosis (WBC 13 × 10⁹/L, ANC 8,476/µL) is most likely a physiologic response to metabolic inflammation associated with NAFLD and metabolic syndrome, but you must systematically rule out bacterial infection—particularly spontaneous bacterial peritonitis if ascites is present—before attributing it to chronic metabolic disease. 1, 2

Immediate Priority: Rule Out Active Infection

Check vital signs immediately to assess for fever (≥38.3°C single measurement or ≥38.0°C sustained for ≥1 hour), hypotension, tachycardia, tachypnea, or altered mental status, as these indicate sepsis requiring urgent intervention. 1, 2

Critical Infection Screening Steps:

• Obtain a manual differential immediately—automated analyzers miss band forms and toxic granulations. An absolute band count ≥1,500 cells/mm³ (likelihood ratio 14.5) or left shift ≥16% bands (likelihood ratio 4.7) strongly indicates bacterial infection even with only mild leukocytosis. 1, 2

• If the patient has cirrhosis with ascites, perform diagnostic paracentesis urgently—any neutrophilia in this population warrants ruling out spontaneous bacterial peritonitis (SBP), which is diagnosed when ascitic fluid neutrophil count exceeds 250 cells/µL and requires immediate antibiotics. 2

• Draw blood cultures before antibiotics if any systemic signs are present (fever, confusion, hemodynamic instability). 1, 2

• Assess for focal infection sources: respiratory symptoms warrant chest imaging; urinary symptoms require urinalysis with culture; abdominal pain with peritoneal signs suggests intra-abdominal infection. 2

Key Red Flags That Mandate Immediate Antibiotics:

• Fever with hemodynamic instability 1
• Altered mental status (especially in older adults with metabolic disease) 2
• Clinical signs of sepsis or high pre-test probability of serious bacterial infection 2
• Recent tick bite with headache, fever, or confusion (consider tick-borne rickettsial diseases) 2

If Infection Is Ruled Out: Metabolic Inflammation

Once you have excluded active bacterial infection through the above systematic evaluation, this mild neutrophilic leukocytosis is consistent with chronic low-grade inflammation associated with NAFLD and metabolic syndrome. 3, 4, 5

Evidence Supporting Metabolic Inflammation:

• Neutrophil-to-lymphocyte ratio (NLR) correlates with NAFLD severity in patients with type 2 diabetes and increases with advancing steatosis grade, reflecting the inflammatory component of metabolic syndrome. 3

• NAFLD is strongly associated with metabolic syndrome—approximately 90% of NAFLD patients have more than one metabolic syndrome feature, and lipotoxicity drives chronic inflammation in both conditions. 4, 5

• The neutrophil percentage of 65% (8,476/13,000) is elevated but does not reach the >90% threshold (likelihood ratio 7.5) that carries the highest probability of serious bacterial infection. 2

Monitoring Strategy:

• Repeat CBC with manual differential in 4-6 weeks to confirm stability rather than progressive increase. 6

• Trending is more important than a single value—if WBC remains stable at 12-14 × 10⁹/L with ANC 8,000-9,000/µL and no left shift, this likely represents chronic metabolic inflammation rather than acute pathology. 6

• Escalate evaluation if WBC rises above 15 × 10⁹/L or ANC exceeds 10,000/µL, as persistent leukocytosis in metabolic disease can rarely indicate progression to more aggressive pathology. 7

Address Underlying NAFLD and Metabolic Risk

Since NAFLD with metabolic syndrome is the primary diagnosis, assess for advanced liver fibrosis using FIB-4 score (calculated from age, ALT, AST, platelet count), as fibrosis stage is the key predictor of liver-related morbidity and mortality. 8

Fibrosis Risk Stratification:

• FIB-4 <1.3 rules out advanced fibrosis with high negative predictive value (92.7%) and requires no immediate hepatology referral. 8

• FIB-4 ≥2.67 indicates high risk for advanced fibrosis or cirrhosis and mandates referral to hepatology for further evaluation with transient elastography or Enhanced Liver Fibrosis (ELF) test. 8

• FIB-4 1.3-2.67 is indeterminate—offer secondary testing (transient elastography, ELF test) or refer for hepatology evaluation. 8

Metabolic Syndrome Management:

• Screen for all metabolic syndrome components: waist circumference ≥94 cm (men)/≥80 cm (women), blood pressure ≥130/85 mmHg, fasting glucose ≥100 mg/dL, triglycerides >150 mg/dL, HDL cholesterol <40 mg/dL (men)/<50 mg/dL (women). 8

• Assess dietary habits and physical activity—high fructose intake, saturated fats, refined carbohydrates, and sedentary behavior all contribute to NAFLD progression. 8

• Do not rely on ALT to monitor disease severity—ALT typically falls as fibrosis progresses, and patients with cirrhosis frequently have normal ALT. 8

Common Pitfalls to Avoid

• Do not dismiss elevated neutrophils when total WBC is only mildly elevated—left shift with normal or mildly elevated WBC still indicates serious bacterial infection if bands are present. 1, 2

• Do not rely on automated differential alone—manual review is essential to identify toxic granulations, vacuolization, left shift, and dysplasia that indicate infection versus chronic inflammation. 1, 2

• Do not ignore progressive leukocytosis—if WBC climbs above 15 × 10⁹/L or shows persistent left shift on serial measurements, consider bone marrow evaluation to exclude myeloproliferative disorder, though this is rare in the metabolic syndrome population. 7

• Do not assume normal liver enzymes exclude advanced fibrosis—use validated non-invasive fibrosis tests (FIB-4, transient elastography) rather than ALT/AST alone. 8