2023 E‑AHPBA/ESSO/ESSR Innsbruck Consensus Guidelines: Preoperative Liver Function Assessment before Hepatectomy (Core Summary)

Basic Information

• Official Title: E‑AHPBA–ESSO–ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy
• Issuing Bodies: European‑African Hepato‑Pancreato‑Biliary Association (E‑AHPBA), European Society of Surgical Oncology (ESSO), European Society for Surgical Research (ESSR)
• Publication: British Journal of Surgery, 2023, 110: 1093–1107; DOI: 10.1093/bjs/znad233
• Methodology: Modified Delphi process (≥85% expert agreement for all statements); SIGN evidence grading; median evidence level 2− to 2+; 21 consensus statements; systematic review of 271 publications
• Core Goal: Standardize preoperative risk stratification to prevent posthepatectomy liver failure (PHLF) (ISGLS definition: elevated INR + hyperbilirubinemia ≥POD5; grades A–C), the leading cause of major morbidity and mortality after liver resection

1. Indications & Timing of Assessment (Strong Recommendations)

1.1 Mandatory Assessment Groups

1. Patients undergoing major/extended major/complex hepatectomy (≥3 segments; complex vascular/mini‑invasive approaches)
2. Known/suspected chronic liver disease (viral, alcoholic, NASH/NAFLD, cirrhosis)
3. Chemotherapy‑associated liver injury (CALI: sinusoidal obstruction, CASH) or drug‑induced liver injury (DILI)
4. Prior liver surgery, portal hypertension, or radiologic signs of parenchymal damage (nodularity, splenomegaly, varices)

• Grade: Strong; median evidence level 2+ (range 3 to 2++)

1.2 Low‑Risk Patients

1.3 Timing

• Perform ≥2–4 weeks preoperatively to allow optimization (weight loss, alcohol cessation, viral suppression) and/or volume/function augmentation (PVE, ALPPS) if needed.

2. Static Blood Markers & Clinical Scores (Foundation of Risk Stratification)

2.1 Routine Laboratory Panel (Strongly Recommended)

• Bilirubin, albumin, AST/ALT, GGT, ALP
• PT/INR, platelet count (portal hypertension marker)
• Hepatitis serology (HBsAg, anti‑HBc, anti‑HCV)
• Creatinine (comorbidity burden)
• Grade: Strong; median evidence level 2− (range 2− to 2+)

2.2 Preferred Clinical Scores (vs. Child–Pugh)

• Key message: Child–Pugh is not a PHLF risk score; ALBI/APRI are preferred for preoperative stratification.

2.3 Portal Hypertension Markers

• Thrombocytopenia (platelets <100×10⁹/L), splenomegaly, varices on imaging = high PHLF risk; mandate advanced functional testing.

3. Morphologic & Functional Imaging (Volume + Function Integration)

3.1 Future Liver Remnant (FLR) Volumetry (Cornerstone)

• Mandatory for all major/complex resections: CT/MRI‑based 3D volumetry (standardized total liver volume, FLR, FLR/body weight, FLR/BSA)
• Thresholds (general guidance; adjusted for parenchymal quality):
  • Normal liver: FLR ≥20–25% total liver volume (TLV) or ≥0.5% FLR/body weight
  • Chronic liver disease/CALI: FLR ≥30–40% TLV
   
• Grade: Strong; evidence level 2+
• Limitation: Volume ≠ function; must combine with functional testing in diseased livers.

3.2 Functional Imaging (Volume + Function in One Exam)

3.2.1 Nuclear Medicine Scintigraphy

• 99mTc‑GSA/IDA scintigraphy: Regional hepatocyte function; segmental FLR function quantification
• Indications: Cirrhosis, CALI, planned extended resections, PVE candidates
• Grade: Weak; evidence level 2− (limited availability)

3.2.2 Functional MRI

• Hepatobiliary contrast‑enhanced MRI (gadoxetate disodium): Combined morphologic staging + hepatocellular function (extraction fraction, excretion rate)
• Advantage: No radiation; integrated oncologic staging + function
• Grade: Weak; evidence level 2− (expertise‑dependent)

3.3 Standard Imaging (CT/MRI)

• Assess parenchymal texture (steatosis, fibrosis, nodularity), splenomegaly, varices, biliary/vascular anatomy; not standalone function assessment.

4. Dynamic Functional Liver Tests (Gold Standard for Parenchymal Capacity)

4.1 Indocyanine Green Clearance (ICG)

• ICG R15 (15‑min retention rate): Most widely validated dynamic test
• Thresholds (context‑dependent):
  • Normal liver: R15 <10% = low risk; 10–20% = caution; >20% = high risk
  • Chronic liver disease: R15 <5–10% may be required for major resection
   
• Use: Combined with FLR volumetry; guides PVE/ALPPS and resection limits
• Grade: Strong; evidence level 2+

4.2 LiMAx® (13C‑Methacetin Breath Test)

• Quantitative maximal hepatic enzymatic function (CYP1A2); point‑of‑care, no radiation
• Threshold: LiMAx <100–150 μg/kg/h = high PHLF risk
• Indications: Cirrhosis, CALI, equivocal ICG; serial monitoring preoperatively
• Grade: Strong; evidence level 2+ (growing European adoption)

4.3 Key Principle

5. Integrated Clinical Algorithm (Consensus Workflow)

1. Basic Stratification (all patients): History + comorbidities + routine labs + ALBI/APRI + CT/MRI volumetry
2. Risk Triage:
   • Low risk: Normal liver, minor resection, ALBI grade 1, normal FLR volume → proceed to surgery
   • Intermediate/high risk: Chronic liver disease/CALI, major resection, ALBI 2/3, low FLR, thrombocytopenia → add dynamic testing (ICG or LiMAx) ± functional imaging
    
3. Decision Thresholds:
   • Unacceptable risk (severe dysfunction/very low FLR): Defer resection; optimize + PVE/ALPPS; consider non‑surgical therapy
   • Borderline risk: Augment FLR (PVE) or stage resection (ALPPS); re‑assess function/volume
   • Acceptable risk: Proceed with standardized parenchymal‑sparing resection
    

6. Key Consensus Statements (Top 10 Clinical Takeaways)

1. Preoperative liver function assessment is mandatory for major/complex resections and all patients with underlying liver disease or CALI/DILI (Strong, 2+).
2. FLR volumetry is the foundation of surgical planning; must be combined with functional testing in diseased livers (Strong, 2+).
3. ALBI/APRI are preferred over Child–Pugh for preoperative PHLF risk stratification (Strong, 2−).
4. ICG R15 or LiMAx are first‑line dynamic tests; choice depends on local availability/expertise (Strong, 2+).
5. Portal hypertension (thrombocytopenia, splenomegaly, varices) mandates advanced functional testing (Strong, 2+).
6. Functional imaging (scintigraphy, gadoxetate MRI) is useful for regional FLR function in complex cases (Weak, 2−).
7. Child–Pugh should not be used as the sole PHLF risk score (Strong, 2+).
8. Preoperative optimization (alcohol cessation, weight loss, viral suppression) improves functional reserve and reduces PHLF risk (Strong, 2+).
9. Low‑risk patients (normal liver, minor resection) may not need dynamic testing (Weak, 2−).
10. The goal is individualized risk‑adapted resection; volume/function augmentation (PVE/ALPPS) is indicated for borderline FLR/function (Strong, 2+).

7. Evidence Gaps & Future Directions

• Lack of high‑level RCTs for most functional tests; need prospective validation of combined volumetry‑function algorithms
• Standardization of ICG/LiMAx thresholds across etiologies (cirrhosis vs. CALI vs. NASH)
• Role of AI‑based radiomics/functional MRI for automated FLR function quantification
• Cost‑effectiveness of routine advanced testing in low‑to‑medium volume centers