Assessment and optimization of liver volume before major hepatic resection: Current guidelines and a narrative review
Executive Summary
Post-hepatectomy liver failure (PHLF) remains the primary cause of morbidity and mortality following major liver resection, complicating up to one-third of procedures. While technological advances have reduced peri-operative mortality to less than 5% in major centers, the risk of PHLF is significantly elevated in patients requiring extended resections or those with underlying liver disease.
The most critical modifiable predictor of PHLF is the volume and quality of the Functional Liver Remnant (FLR)—the portion of the liver remaining after surgery. This briefing document synthesizes current guidelines for assessing the FLR and outlines optimization strategies, such as Portal Vein Embolization (PVE) and Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), designed to induce liver hypertrophy and improve surgical candidacy.
1. Post-Hepatectomy Liver Failure (PHLF)
PHLF is characterized by the post-resection failure of the liver’s synthetic and excretory functions. Clinical manifestations include prolonged prothrombin time, hyperbilirubinemia, elevated serum lactate, hypoalbuminemia, hypoglycemia, and hepatic encephalopathy.
1.1 Predictive Criteria and Grading
The 50-50 Criteria: Established by Balzan et al. (2005), this metric identifies high-risk patients on post-operative day 5. It is defined as a Prothrombin Index <50% (INR >1.7) and Serum Bilirubin >50 μmol/L (2.9 mg/dl). Meeting these criteria indicates a 59% mortality risk.
ISGLS Grading System: The International Study Group of Liver Surgery classifies PHLF by clinical impact:
Grade A: Deterioration requiring no change in clinical management; no increase in mortality.
Grade B: Change in clinical pathway required, but non-invasive. Mortality risk: 12%.
Grade C: Requires invasive procedures. Mortality risk: 54%.
1.2 Pathogenesis
The liver possesses a unique regenerative capacity, typically restoring mass and function within weeks. However, PHLF occurs when the FLR is insufficient to maintain homeostasis (Small for Size Syndrome) or when regeneration is inhibited by factors such as ischemia-reperfusion injury, parenchymal congestion, or sepsis.
2. Risk Factors for PHLF
The risk of liver failure is multifactorial, spanning patient demographics, liver health, and surgical variables.
3. The Functional Liver Remnant (FLR)
The FLR is calculated as a percentage: (Total Liver Volume - Tumor Volume) / Remaining Functional Volume. Resection of five or more Couinaud segments (extended hepatectomy) significantly increases PHLF risk.
3.1 Minimum Volume Thresholds
The safe limit for resection varies based on the quality of the underlying parenchyma:
Healthy Liver: Minimum FLR of 20%.
Mild Disease: (Mild steatosis/cholestasis or Child-Pugh A) Minimum FLR of 30–35%.
Severe Disease: (Severe steatosis/cholestasis) Minimum FLR of 40–45%.
Cirrhosis: While some Child-Pugh A patients can tolerate 50% resection, those with portal hypertension or advanced cirrhosis (Child-Pugh B/C) are at high risk even with minor resections.
3.2 Volumetric and Functional Assessment
Imaging: CT and MRI, often with 3D reconstruction, are used to calculate Total Liver Volume (TLV) and FLR.
Indocyanine Green (ICG) Clearance: This is the most common functional test. An ICG retention rate at 15 minutes (ICGR15) above 15–20% indicates impaired reserve and necessitates volume optimization.
4. Volume Optimization Strategies
When the predicted FLR is below safe thresholds, strategies to induce hypertrophy in the remnant liver are employed.
4.1 Portal Vein Embolization (PVE)
PVE is the "gold standard" for volume optimization, technically feasible in over 90% of cases.
Mechanism: Occluding portal flow to the side being resected redirects blood to the FLR, triggering cellular hypertrophy.
Results: FLR volume typically increases by 40–62% over 3–6 weeks.
Surgical Timing: Resection is usually performed 4–6 weeks post-PVE. An FLR hypertrophy response of <5% is a relative contraindication for resection.
4.2 Yttrium-90 (Y90) Radioembolization
Known as "radiation lobectomy," this transarterial treatment provides a dual advantage:
Tumor Control: Induces tumor necrosis and reduces the risk of progression during the wait period.
Hypertrophy: Induces approximately 30% FLR growth. While beneficial, this is significantly less than the hypertrophy achieved by PVE (29% vs. 61% in matched studies).
4.3 Portal Vein Ligation (PVL) and Two-Stage Hepatectomy
Reserved for bilateral tumors, the first stage involves clearing the FLR of tumors and ligating the contralateral portal vein. After 4–6 weeks, if 30–43% growth is achieved, the second stage (resection) is performed. This approach is less favored than PVE due to the requirement for two major surgeries.
4.4 Associating Liver Partition and Portal Vein Ligation (ALPPS)
ALPPS is a more aggressive, two-stage surgical technique.
Advantages: It induces the fastest FLR growth (up to 80% in one week), minimizing the risk of tumor progression during the wait period.
Disadvantages: It carries significantly higher morbidity (73%) and mortality (14%) compared to PVE (mortality ~7%).
Indications: Primarily considered for patients with extremely low initial FLR or as a "salvage" procedure for those who fail to hyper-trophy after PVE.
5. Conclusion
Optimizing the FLR is the most effective strategy for mitigating the risk of post-hepatectomy liver failure. PVE remains the primary modality for volume optimization due to its safety and efficacy. While ALPPS offers rapid hypertrophy, its high complication rate necessitates careful patient selection. Future advancements in liver-assist devices and regenerative medicine are expected to further improve the safety profile of major hepatic resections.
