Effect and Mechanism of ALPPS Operation on Liver Regeneration

Official title

Effect and Mechanism of Combined Hepatectomy and Portal Vein Ligation Staged Hepatectomy (ALPPS) on Liver Regeneration in Patients With Hepatobiliary Malignancy

Overview

Hepatobiliary malignancies-principally hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA)-are highly aggressive and often diagnosed at advanced stages. Curative-intent liver resection remains the standard for resectable disease; however, postoperative outcomes depend on an adequate functional future liver remnant (FLR). Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) induces rapid FLR hypertrophy and has expanded resection eligibility compared with conventional two-stage hepatectomy by shortening the interval to definitive resection. Key uncertainties persist regarding the quality of ALPPS-induced regeneration and its relationship to long-term oncologic outcomes, including recurrence and metastasis. This observational study enrolls patients deemed suitable for ALPPS at Peking Union Medical College Hospital. Perioperative care follows institutional standards; no therapeutic procedures are altered for research purposes. The investigators will collect clinically available liver tissue and relevant medical data obtained during standard surgical care to characterize cellular and molecular programs of regeneration across the ALPPS stages. High-throughput profiling-including single-cell and spatial transcriptomics-will be used to define cell-type composition, transcriptional states, and signaling pathways associated with regeneration. The primary objective is to describe cellular and gene-expression changes in regenerating liver induced by ALPPS. Secondary objectives include exploring associations between regenerative quality and short- and long-term clinical outcomes. Findings are expected to inform potential therapeutic targets and strategies to enhance safe regeneration and improve postoperative prognosis.

Interventions

• Procedure ALPPS
  In recent years, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) provides new hope for the solution of large/unresectable hepatobiliary malignancies. This technique promotes the rapid proliferation and regeneration of the remaining liver by separating the liver and ligation of the portal vein, so that the patients whose original liver function is not enough to tolerate large-scale liver resection can complete liver regeneration in a short time, so as to perfor

Primary outcome measures

• Residual liver volume [Time frame: Time Frame: Day 7 (±2 days) and Day 14 (±2 days) after Stage-1 ALPPS; primary analysis uses the last assessment obtained prior to Stage-2 (up to Day 28).]

Eligibility criteria

Inclusion criteria

• Age: Patients aged 18 to 75 years
• Diagnosis established: A diagnosis of hepatobiliary malignancy (including hepatocellular carcinoma and cholangiocarcinoma) was confirmed and evaluated as suitable for ALPPS surgery
• Liver function status: preoperative Child-Pugh score A or B, MELD score ≤15, with sufficient liver function reserve for operation
• Tumor characteristics: bilobal or complex tumors of the liver with large tumor areas requiring ALPPS to ensure adequate residual liver volume (FLR/TLV<30% or FLR/BW<0.5)
• Preoperative assessment: Imaging showed that future liver residual (FLR) was insufficient to support standard hepatectomy, and liver volume must be increased by ALPPS
• FLR enlargement: Postoperative assessment of FLR enlargement as expected (at least 30% enlargement or FLR/BW above 0.5) for a second procedure
• No distant metastases: No unresectable extrahepatic metastases, except for resectable lung metastases

Exclusion criteria

• Preoperative FLR insufficiency: Residual liver volume (FLR) did not increase sufficiently after the first step (<30% increase or FLR/BW <0.5) to be suitable for the second step
• Extrahepatic metastasis: unresectable distant metastasis, such as extensive metastasis of bone, lung, etc
• Severe liver disease: very poor liver function before surgery, Child-Pugh grade C or severe liver sclerosis during surgery (e.g. Metavir≥F3 or 30% or more hepatic steatosis)
• Major comorbidities: Major illnesses such as severe cardiovascular disease, kidney failure, or respiratory failure that do not tolerate major surgery
• Postoperative complications: Serious postoperative complications (such as liver failure, infection, etc.) after the first step are not suitable for the second step
• Evaluation of adverse surgery: After the first procedure, FLR blood supply or function is abnormal, affecting liver regeneration
• Pregnancy and lactation: pregnant or lactating women

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Publications

• Wen Z, Jin Z, Xu B, Zhu H, Wang J, Chen W, Zhang J, Huang K, Lan Z, Meng B, Mao W, Zhu H, Zhang L, Lu T, Zeng J, Bao L, Lau WY, Guo Y. Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), a novel ALPPS procedure for the treatment of hepatocellular carcinoma with severe fibrosis: retrospective clinical cohort study. Int J Surg. 2024 Sep 1;110(9):5662-5671. doi: 10.1097/JS9.0000000 PMID 38768472

Identifiers

NCT: NCT07142213 · K7100

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗