Liver Regeneration

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.

Posthepatectomy liver failure (PHLF) remains a significant life-threatening problem after major hepatectomies. Pentoxifylline is shown to have potent vasodilating properties for peripheral blood vessels, along with the hepatic vasculature. In a Double-blinded, randomized, controlled trial (RCT) at a single tertiary care center (2006-2009) by Petrowsky, Henrik et al (Annals of Surgery, November 2010) on 101 Non-cirrhotic patients undergoing major Hepatectomy, they demonstrated beneficial effects of Pentoxifylline on regeneration of small remnant livers (RLBW ratio ≤ 1.2%). In mice model, pentoxifylline (Tian, Yinghua, et al Proceedings of the National Academy of Sciences 103.12 (2006)) is shown to confer protective effects against small-for-size syndrome in arterialized small-for-size liver transplantation. This Randomised control trial is being conducted to analyze the effect of Pentoxifylline supplementation in live donors undergoing donor hepatectomy with respect to markers of anatomical regeneration in a high volume liver transplant center in India.

the investigators will pursue two specific aims: (1) to monitor the extent of heme oxygenase induction (by measuring endogenous CO production) in relationship to the extent of hepatic resection (2) to assess the production of CO in patients following liver resection and correlate these findings to the rate of liver regeneration and liver function.

The primary objective of this interventional study is determine if the future liver remnant can be optimized by improving liver function pre-operatively in patients who are scheduled for major hepatectomy. The main questions it aims to answer are: 1. Does high-dose insulin therapy improve liver function in the pre-operative setting? 2. What is the effect of high-dose insulin therapy on liver function and liver regeneration after a liver venous deprivation (LVD) procedure? 3. What is the relationship between volume hypertrophy and function in the regenerating liver? Participants will receive a 6-hour infusion of insulin and dextrose to maintain a hyperinsulinemic-normoglycemic state in the weeks prior to planned liver surgery to assess its effect on liver function measured by 99m-Tc-Mebrofenin hepatobiliary scintigraphy.