Should a 65-year-old male patient with Chronic Liver Disease (CLD) and a hydatid cyst, Model for End-Stage Liver Disease (MELD) score of 9, Child-Pugh class A, leukopenia (White Blood Cell count of 2000) and neutropenia (neutrophil count of 42%), be given Neukine (filgrastim) to improve neutrophil count before undergoing surgery?

Preoperative Management of Neutropenia in a CLD Patient with Hydatid Cyst

Direct Answer

Do not administer Neukine (filgrastim) preoperatively for this patient, and proceed with surgery only after careful risk stratification confirms acceptable perioperative mortality risk below 3%. 1

Surgical Risk Assessment for This Patient

Current Risk Profile

This 65-year-old male presents with:

• Child-Pugh Class A cirrhosis (favorable for surgery) 1
• MELD score of 9 (low mortality risk, well below transplant threshold of ≥15) 2, 3
• Leukopenia (WBC 2000) with neutropenia (42% = ~840 cells/mm³) (moderate neutropenia)
• Hydatid cyst requiring surgical intervention

Key Surgical Fitness Criteria

For liver resection in cirrhotic patients, the following must be assessed: 1

1. Liver function parameters:

   • Child-Pugh Class A is acceptable for surgery 1
   • MELD 9 indicates low short-term mortality risk 2, 3
   • Portal hypertension status must be evaluated (clinically significant portal hypertension with HVPG >10 mmHg is an absolute contraindication) 1

2. Future liver remnant (FLR) volume:

   • For Child-Pugh A patients, FLR should be ≥30-40% of total liver volume 1
   • CT volumetry should be performed to calculate FLR-to-total liver volume ratio 1

3. Laboratory-based risk assessment:

   • Include ALBI score, ICG retention test, and platelet count 1
   • Ensure bilirubin ≤1.5 mg/dL for optimal outcomes 1

4. Portal hypertension screening:

   • Check for varices via endoscopy or liver stiffness measurement 1
   • Liver stiffness <17 kPa by VCTE suggests absence of high-risk varices 1
   • Presence of ascites or clinical signs of portal hypertension require further evaluation 1

Why Filgrastim Should NOT Be Used

Lack of Evidence in Surgical Prophylaxis for Chronic Liver Disease

There is no clear evidence that G-CSF reduces infection rates or improves outcomes in cirrhotic patients undergoing surgery. 1

• The EASL guidelines explicitly state: "There is no evidence from prospective trials that the use of granulocyte colony-stimulating factor (G-CSF) reduces the rate of infections and/or improves SVR rates" in cirrhotic patients 1
• While G-CSF is sometimes used when neutrophil counts drop below 500-750/mm³ in hepatitis C treatment, "there is insufficient evidence to recommend this practice as standard treatment" 1

Patient's Neutrophil Count Is Not Critically Low

• Absolute neutrophil count (ANC) of ~840 cells/mm³ (42% of 2000) is moderate neutropenia, not severe 1
• Severe neutropenia requiring intervention is typically defined as ANC <500/mm³ 1
• The patient's neutropenia is likely secondary to hypersplenism from portal hypertension, which is common in cirrhosis 1

Potential Risks of Filgrastim

Serious adverse effects documented with filgrastim include: 4

• Splenic rupture and splenomegaly (particularly concerning in cirrhotic patients who may already have splenomegaly) 4
• Acute respiratory distress syndrome 4
• Capillary leak syndrome 4
• Leukocytosis (which could complicate postoperative monitoring) 4
• Rare but severe pneumonitis requiring ICU admission 5

Limited Benefit in Non-Chemotherapy Settings

• Most evidence for filgrastim efficacy exists in chemotherapy-induced neutropenia 6, 7
• One small study (n=24) in cancer neck dissection showed reduced wound infections with preoperative filgrastim 8, but this was in cancer surgery patients, not cirrhotic patients with chronic neutropenia
• The mechanism of neutropenia differs: chemotherapy-induced (bone marrow suppression) versus cirrhosis-related (hypersplenism, decreased thrombopoietin production) 1

Recommended Preoperative Fitness Assessment

Essential Evaluations Before Surgery

1. Comprehensive liver function assessment: 1

   • Complete Child-Pugh scoring (confirm Class A status)
   • Calculate MELD-Na score 2
   • Measure serum albumin, bilirubin, INR, creatinine 1, 2
   • Perform ICG retention test if available 1
   • Calculate ALBI score 1

2. Portal hypertension evaluation: 1

   • Upper endoscopy to assess for esophageal varices 1
   • Liver stiffness measurement by VCTE (cutoff <17 kPa suggests low risk of varices) 1
   • Clinical assessment for ascites, splenomegaly 1
   • Platelet count (thrombocytopenia suggests portal hypertension) 1

3. Volumetric assessment (if liver resection planned): 1

   • CT or MRI volumetry to calculate FLR 1
   • Ensure FLR ≥30-40% for Child-Pugh A patients 1
   • Consider portal vein embolization if FLR inadequate 1

4. Infection risk stratification: 1

   • Current infection screening (urinalysis, chest X-ray)
   • Ensure no active infections before surgery
   • Optimize nutritional status (albumin, prealbumin levels)

5. Cardiopulmonary assessment: 1

   • ECG, echocardiography if indicated
   • Pulmonary function tests if respiratory symptoms present
   • Performance status evaluation

Specific Contraindications to Identify

Absolute contraindications to liver resection: 1

• Clinically significant portal hypertension (HVPG >10 mmHg) 1
• Child-Pugh Class B or C 1
• Presence of ascites 1
• Inadequate FLR volume 1
• Active infection 1

Perioperative Management Strategy

Preoperative Optimization

1. Correct coagulopathy if present: 1

   • Target INR <1.5 if possible
   • Consider vitamin K supplementation
   • Fresh frozen plasma only if active bleeding or urgent surgery

2. Nutritional support: 1

   • Ensure adequate protein intake
   • Correct vitamin deficiencies
   • Target albumin >3.0 g/dL if possible

3. Infection prophylaxis: 8, 9

   • Standard perioperative antibiotics (cefotiam 25 mg/kg + metronidazole 20 mg/kg or equivalent) 8
   • Do not add filgrastim given lack of evidence and potential risks 1

Intraoperative Considerations

• Minimize blood loss (use of cell saver, meticulous hemostasis) 1
• Avoid prolonged operative time 1
• Maintain adequate perfusion pressure 1

Postoperative Monitoring

1. Monitor for post-hepatectomy liver failure (PHLF): 1

   • Daily bilirubin, INR, creatinine 1
   • Watch for ascites, encephalopathy 1

2. Infection surveillance: 8, 9

   • Monitor for wound infection, pneumonia, urinary tract infection
   • Early intervention with appropriate antibiotics if infection develops
   • The neutropenia itself should not preclude surgery if other parameters are acceptable 1

3. Hematologic monitoring:

   • Serial CBC to track WBC recovery
   • Platelet transfusion threshold <50,000/mm³ for active bleeding 1

Common Pitfalls to Avoid

1. Do not delay necessary surgery solely due to moderate neutropenia (ANC ~840/mm³) in the absence of active infection 1

2. Do not use filgrastim without evidence of benefit in cirrhotic surgical patients, as it may cause serious adverse effects without proven efficacy 1, 4

3. Do not proceed with surgery if clinically significant portal hypertension is present (this is an absolute contraindication regardless of neutrophil count) 1

4. Do not rely solely on MELD or Child-Pugh scores—use multi-parametric assessment including volumetry, portal hypertension evaluation, and functional tests 1

5. Do not ignore the underlying cause of neutropenia (likely hypersplenism from portal hypertension)—this should be factored into overall surgical risk assessment 1