Porcine model for the study of liver regeneration enhanced by non-invasive 13C-methacetin breath test (LiMAx test) and permanent portal venous access

Abstract

Introduction Despite advances in perioperative management and surgical technique, postoperative liver failure remains a feared complication after hepatic resection. Various supportive treatment options are under current discussion, but lack of structured evaluation. We therefore established a porcine model of major liver resection to study regeneration after partial hepatectomy in a reliable and well-defined pre-clinical setting. Methods Major hepatectomy was performed on seven minipigs with the intention to set up a non-lethal but relevant transient impairment of liver function. For steady postoperative vascular access (e.g. for blood withdrawal, measurement of venous pressure), permanent catheters were implanted into the internal jugular and portal veins, respectively. Animals were followed up for 30 days; clinical and laboratory results were recorded in detail. Monitoring was enhanced by non-invasive determination of the maximum liver function capacity (LiMAx test). Results and conclusions The established porcine model appeared suitable for evaluation of postoperative liver regeneration. Clinical characteristics and progression of liver function impairment as well as subsequent recovery were comparable to courses known from surgery in humans. Laboratory parameters (e.g. liver enzymes, bilirubin, INR, coagulation factor II) showed relevant derangements during postoperative days (POD) 0 to 3 followed by normalization until POD 7. Application of the LiMAx test was feasible in minipigs, again showing values comparable to humans and kinetics in line with obtained laboratory parameters. The exteriorized portal vein catheters enabled intra- and postoperative monitoring of portal venous pressures as well as easy access for blood withdrawal without relevant risk of postoperative complications.

Supportive Hepatocyte Transplantation after Partial Hepatectomy Enhances Liver Regeneration in a Preclinical Pig Model

“…1b) as described previously [7]. The liver weight of the animals was estimated as follows: 491.86 × LN (BW in kg) – 1,249.8 [6]. The FLR was calculated as follows: 100 – (resected liver weight in kg × 100/estimated liver weight in kg).…”

“…In all animals, partial hepatectomy was performed as a subtotal resection on 3 of 5 liver lobes, aiming for a FLR of about 50% (Fig. 1a) as previously described [6]. In brief, liver resection was performed with vascular clamps and monopolar dissection, or with a linear stapler, depending on the anatomical conditions of the respective liver lobes.…”

“…The maximum liver function capacity (LiMAx test) is based on the quantification of 13 C-methacetin metabolism by the liver-specific cytochrome P450 1A2 system [11]. As previously described [6], a cone-shaped mouthpiece was placed on the animal's snout to measure the 13 CO 2 / 12 CO 2 ratio within the exhaled air. The Li-MAx measurements were performed in each animal, after fasting for at least 8 h, at the following time points: 5 days before the operation (day -5), intraoperatively directly after liver resection, and on POD 3, 7, and 15, respectively.…”

“…Exactly which patients would benefit most from HTx remains a matter of debate. Previously, we developed a porcine model of liver regeneration after partial hepatectomy with a future liver remnant (FLR) of 50% [6]. The aim of this study was to analyze if supportive HTx is safe and effectively enhances liver regeneration in the setting of partial hepatectomy.…”

Gut microbiome dysbiosis in patients with hepatitis B virus-related hepatocellular carcinoma after extended hepatectomy liver failure

“…As an intrinsic risk of mortality and a life-threatening complication, PHLF is a particular focus for hepatic surgeons in clinical practice. At present, different scoring methods of multiple clinical factors can predict the incidence and outcomes of PHLF (15); however, the basic treatment options are limited to standard intensive care measures, such as mechanical ventilation, vasopressor therapy, dialysis, and administration of coagulation factors and albumin, which provide unsatisfactory results (16). Thus, the development of a comprehensive evaluation system and effective treatment options are urgently required for PHLF.…”