Experimental evaluation of liver regeneration patterns and liver function following ALPPS

Area of Science:

• Hepatology
• Surgical Oncology
• Regenerative Medicine

Background:

• The mechanisms governing liver regeneration following Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) remain incompletely understood.
• Evaluating the interplay between future liver remnant (FLR) volume, regenerative capacity, and functional recovery is crucial for optimizing ALPPS outcomes.

Purpose of the Study:

• To investigate the relationship between FLR volume and liver regeneration characteristics.
• To assess the restoration of liver function in relation to FLR size after ALPPS in an experimental model.

Main Methods:

• An experimental rat model of ALPPS was established, involving selective portal vein ligation (PVL), parenchymal transection, and partial hepatectomy (Step 1), followed by liver resection (Step 2).
• Groups with varying FLR sizes (30%, 20%, 10%) were compared to sham-operated controls and animals undergoing a different surgical procedure (left lateral lobe resection with 90% PVL).
• Outcomes assessed included morbidity, mortality, liver regeneration dynamics, and functional parameters.

Main Results:

• The smallest FLR group (ALPPS10) exhibited significant mortality after Step 1 and high rates of ascites post-Step 2.
• Despite the highest relative FLR size increase and growth rates in ALPPS groups, smaller FLR sizes correlated with persistent elevations in liver enzymes (aminotransferases, bilirubin) and decreased albumin.
• Histological analysis revealed severe sinusoidal injury and increased markers of proliferation and hepatic progenitor cell activation in animals with small FLRs.

Conclusions:

• A significant discordance exists between the degree of FLR volume expansion and the functional recovery of the liver after ALPPS.
• FLR volume alone is an insufficient predictor of functional liver restoration post-ALPPS.