Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis.

Backgrounds/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. Methods: We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. Results: The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). Conclusions: HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

Revealing the three-dimensional arrangement of polar topology in nanoparticles.

In the early 2000s, low dimensional ferroelectric systems were predicted to have topologically nontrivial polar structures, such as vortices or skyrmions, depending on mechanical or electrical boundary conditions. A few variants of these structures have been experimentally observed in thin film model systems, where they are engineered by balancing electrostatic charge and elastic distortion energies. However, the measurement and classification of topological textures for general ferroelectric nanostructures have remained elusive, as it requires mapping the local polarization at the atomic scale in three dimensions. Here we unveil topological polar structures in ferroelectric BaTiO3 nanoparticles via atomic electron tomography, which enables us to reconstruct the full three-dimensional arrangement of cation atoms at an individual atom level. Our three-dimensional polarization maps reveal clear topological orderings, along with evidence of size-dependent topological transitions from a single vortex structure to multiple vortices, consistent with theoretical predictions. The discovery of the predicted topological polar ordering in nanoscale ferroelectrics, independent of epitaxial strain, widens the research perspective and offers potential for practical applications utilizing contact-free switchable toroidal moments.

In vitro selection of a trans aptamer complex for target-responsive fluorescence activation.

BACKGROUND: Most biological molecular complexes consist of multiple functional domains, yet rationally constructing such multifunctional complexes is challenging. Aptamers, the nucleic acid-based functional molecules, can perform multiple tasks including target recognition, conformational changes, and enzymatic activities, while being chemically synthesizable and tunable, and thus provide a basis for engineering enhanced functionalities through combination of multiple units. However, the conventional approach of simply combining aptamer units in a serial manner is susceptible to undesired crosstalk or interference between the aptamer units and to false interactions with non-target molecules; besides, the approach would require additional mechanisms to separate the units if they are desired to function independently. It is clearly a challenge to develop multi-aptamer complexes that preserve independent functions of each unit while avoiding undesired interference and non-specific interactions. RESULTS: By directly in vitro selecting a 'trans' aptamer complex, we demonstrate that one aptamer unit ('utility module') can remain hidden or 'inactive' until a target analyte triggers the other unit ('sensing module') and separates the two aptamers. Since the operation of the utility module occurs free from the sensing module, unnecessary crosstalk between the two units can be avoided. Because the utility module is kept inactive until separated from the complex, non-specific interactions of the hidden module with noncognate targets can be naturally prevented. In our demonstration, the sensing module was selected to detect serotonin, a clinically important neurotransmitter, and the target-binding-induced structure-switching of the sensing module reveals and activates the utility module that turns on a fluorescence signal. The aptamer complex exhibited a moderately high affinity and an excellent specificity for serotonin with ∼16-fold discrimination against common neurotransmitter molecules, and displayed strong robustness to perturbations in the design, disallowing nonspecific reactions against various challenges. SIGNIFICANCE: This work represents the first example of a trans aptamer complex that was in vitro selected de novo. The trans aptamer complex selected by our strategy does not require chemical modifications or immediate optimization processes to function, because the complex is directly selected to perform desired functions. This strategy should be applicable to a wide range of functional nucleic acid moieties, which will open up diverse applications in biosensing and molecular therapeutics.

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule.

BACKGROUND/AIMS: Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases. METHODS: Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated. RESULTS: All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038). CONCLUSIONS: Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

A single-center experience of over 300 cases of single-incision robotic cholecystectomy comparing the da Vinci SP with the Si/Xi systems.

Minimally invasive surgery is usually more beneficial than open surgeries in various fields of surgery. With the newly developed Single-Port (SP) robotic surgical system, even single-site surgery has become easier to access. We compared single-incision robotic cholecystectomy between the Si/Xi and SP systems. This retrospective single-center study enrolled patients who underwent single-incision robotic cholecystectomy between July 2014 and July 2021. The clinical outcomes of the da Vinci Si/Xi and SP systems were compared. In total, 334 patients underwent single-incision robotic cholecystectomy (118 Si/Xi vs. 216 SP). The SP group had more chronic or acute cholecystitis than the Si/Xi group did. There was more bile spillage in the Si/Xi group during the surgery. The total operative and docking times were significantly shorter in the SP group. There was no difference in the postoperative outcomes. The SP system is safe and feasible regarding comparable postoperative complication rates and is more convenient regarding docking and techniques.

Molecular Complementarity of Proteomimetic Materials for Target-Specific Recognition and Recognition-Mediated Complex Functions.

As biomolecules essential for sustaining life, proteins are generated from long chains of 20 different α-amino acids that are folded into unique 3D structures. In particular, many proteins have molecular recognition functions owing to their binding pockets, which have complementary shapes, charges, and polarities for specific targets, making these biopolymers unique and highly valuable for biomedical and biocatalytic applications. Based on the understanding of protein structures and microenvironments, molecular complementarity can be exhibited by synthesizable and modifiable materials. This has prompted researchers to explore the proteomimetic potentials of a diverse range of materials, including biologically available peptides and oligonucleotides, synthetic supramolecules, inorganic molecules, and related coordination networks. To fully resemble a protein, proteomimetic materials perform the molecular recognition to mediate complex molecular functions, such as allosteric regulation, signal transduction, enzymatic reactions, and stimuli-responsive motions; this can also expand the landscape of their potential bio-applications. This review focuses on the recognitive aspects of proteomimetic designs derived for individual materials and their conformations. Recent progress provides insights to help guide the development of advanced protein mimicry with material heterogeneity, design modularity, and tailored functionality. The perspectives and challenges of current proteomimetic designs and tools are also discussed in relation to future applications.

Should we be reluctant to perform pancreatectomy in patients with chronic liver disease? A single center 10-year experience.

PURPOSE: Many studies have shown extra-hepatic surgery in patients with chronic liver disease (CLD) with or without portal hypertension can result in complications. The aim of this study was to analyze the results of major pancreatectomy in patients with CLD including cirrhosis and to evaluate their efficacy and safety. METHODS: We retrospectively reviewed 319 patients undergoing open pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in our center. Those who received PD and DP in patients without CLD were classified into groups A and D, and those with CLD into groups B and C, respectively. Group B and C were subdivided into groups 1 and 2 according to the presence of portal hypertension. RESULTS: Forty-three patients (13.5%) had CLD. Of the 221 patients who received PD, 25 had CLD. Of the 98 patients who received DP, 18 (Group C) had CLD. In the PD group, patients with portal hypertension (group B1) had longer operative time. However, the transfusion rate and complication rate were not significantly different from other groups. There was no mortality in patients with CLD without portal hypertension (group B2) and the complication and mortality rate was comparable to patients with normal liver function (group A). In the DP group, the transfusion rate, complication rate and mortality rate were significantly higher in patients with portal hypertension (group C1). CONCLUSIONS: Acceptable outcomes were obtainable following pancreatic surgery in cirrhotic, non-portal hypertensive patients with surgical outcomes equivalent to non-cirrhotic patients.AbbreviationsCLDchronic liver diseasePDpancreaticoduodenectomyDPdistal pancreatectomy.

Direct strain correlations at the single-atom level in three-dimensional core-shell interface structures.

Nanomaterials with core-shell architectures are prominent examples of strain-engineered materials. The lattice mismatch between the core and shell materials can cause strong interface strain, which affects the surface structures. Therefore, surface functional properties such as catalytic activities can be designed by fine-tuning the misfit strain at the interface. To precisely control the core-shell effect, it is essential to understand how the surface and interface strains are related at the atomic scale. Here, we elucidate the surface-interface strain relations by determining the full 3D atomic structure of Pd@Pt core-shell nanoparticles at the single-atom level via atomic electron tomography. Full 3D displacement fields and strain profiles of core-shell nanoparticles were obtained, which revealed a direct correlation between the surface and interface strain. The strain distributions show a strong shape-dependent anisotropy, whose nature was further corroborated by molecular statics simulations. From the observed surface strains, the surface oxygen reduction reaction activities were predicted. These findings give a deep understanding of structure-property relationships in strain-engineerable core-shell systems, which can lead to direct control over the resulting catalytic properties.

Prevalence and clinical significance of pancreatic cystic lesions in immunosuppressed patients following solid organ transplantation.

Background: Pancreatic cystic lesions (PCLs) are occasionally found in solid organ transplant (SOT) recipients. In such recipients, the risk of cancer is increased due to immunosuppressive therapy. This study investigated the prevalence of PCLs and described their clinical course in immunosuppressed patients following SOT. Methods: The presence of PCLs in a retrospective cohort of 805 consecutive SOT recipients from 2009 to 2019 was examined. The characteristics of PCLs were compared using initial and follow-up imaging, where available. These results were compared to an age- and sex-matched immunocompetent control group monitored for at least 12 months. Results: PCLs were present in 15 of 805 SOT patients (seven liver and eight kidney transplantations). The median diameter of the largest lesion was 20 mm (range, 0.2-60 mm) and 60% of lesions were benign. During follow-up imaging, the cyst size remained stable in 46.7%, increased in 13.3%, and decreased in 40.0% of the SOT group. Significantly more of the SOT patients showed PCL size reductions (P=0.007). Among SOT patients diagnosed with intraductal papillary mucinous neoplasms (6/15), worrisome features were noted in one patient at the time of cyst diagnosis. Differences in the development of worrisome features between the study and control groups were not statistically significant. Conclusions: The malignant transformation of PCLs in SOT recipients is rare and most such PCLs can be managed conservatively. The presence of a PCL should therefore not affect transplant eligibility.

Selective RNA Labeling by RNA-Compatible Type II Restriction Endonuclease and RNA-Extending DNA Polymerase.

RNAs not only offer valuable information regarding our bodies but also regulate cellular functions, allowing for their specific manipulations to be extensively explored for many different biological and clinical applications. In particular, rather than temporary hybridization, permanent labeling is often required to introduce functional tags to target RNAs; however, direct RNA labeling has been revealed to be challenging, as native RNAs possess unmodifiable chemical moieties or indefinable dummy sequences at the ends of their strands. In this work, we demonstrate the combinatorial use of RNA-compatible restriction endonucleases (REs) and RNA-extending polymerases for sequence-specific RNA cleavage and subsequent RNA functionalization. Upon the introduction of complementary DNAs to target RNAs, Type II REs, such as AvrII and AvaII, could precisely cut the recognition site in the RNA-DNA heteroduplexes with exceptionally high efficiency. Subsequently, the 3' ends of the cleaved RNAs were selectively and effectively modified when Therminator DNA polymerase template-dependently extended the RNA primers with a variety of modified nucleotides. Based on this two-step RNA labeling, only the target RNA could be chemically labeled with the desired moieties, such as bioconjugation tags or fluorophores, even in a mixture of various RNAs, demonstrating the potential for efficient and direct RNA modifications.

Left liver graft in adult-to-adult living donor liver transplantation with an optimal portal flow modulation strategy to overcome the small-for-size syndrome - A retrospective cohort study.

BACKGROUND: Adult-to-adult living donor liver transplantation (LDLT) is a notable type of liver transplantation. Several centers prefer the right liver graft (RLG) over the left liver graft (LLG) for better recovery of recipients. We compared the outcomes of donors and recipients between LDLT using LLGs and RLGs. MATERIALS AND METHODS: The study cohort comprised of 25 patients in the LLG group and 93 in the RLG group. When both hemiliver grafts met the selection criteria, an LLG was preferred. When portal flow (≥300 ml/min/100gLW) and hepatic venous pressure gradient (≥10 mmHg) were increased, intraoperative splenic artery ligation was performed for portal modulation. Postoperatively, somatostatin was administered when small-for-size syndrome (SFSS) was highly suspected. RESULTS: The graft-to-recipient weight ratio was lower in the LLG group than in the RLG group. There was no significant complication above Clavien-Dindo grade IIIA in donors. Regarding recipient outcomes, SFSS occurred in four (16.0%) patients in the LLG group and three (3.2%) in the RLG group (P = 0.036). Splenic artery ligation was frequently performed in the LLG group than the RLG group (5 [20.0%] vs. 12 [12.9%], P = 0.035) and 5 patients received intravenous continuous somatostatin for 7 (5-12) days. SFSS-related hospital mortality did not occur. There was no significant difference in the short-term and long-term outcomes between the groups. CONCLUSION: This study demonstrates the comparable outcomes of donors and recipients between the LLG and RLG groups although with a higher risk of SFSS that needs high experience to avoid severe complications and graft loss. We expect LLG to be used more actively in adult-to-adult LDLT with portal flow modulation strategies to overcome fatal SFSS.

Right posterior bile duct stricture after central bisectionectomy or anterior sectionectomy.

PURPOSE: Before performing anterior sectionectomy (AS) or central bisectionectomy (CBS), the anatomy of the right posterior bile duct (RPBD) must be cautiously assessed owing to the many variations of the RPBD and its variations could be related to bile duct injury. METHODS: Clinical data of patients who underwent AS or CBS from 2009 to 2018 were reviewed. The bile duct anatomy according to Okubo's criteria and the right bile duct (RBD) length were evaluated using MRI, and we performed a risk factor analysis of the RPBD stricture (RPBDS). RESULTS: A total of 68 patients were included. Type A bile ducts were the most common (n = 36, 52.9%). Five (7.2%) patients had RPBDS requiring intervention. RPBDS only occurred in patients with a type A bile duct and a type A portal vein undergoing surgery using the Glissonian sheath approach. Moreover, when the RBD length was > 12 mm, the sensitivity and specificity were 0.8 and 0.889, respectively. In multivariate analysis, RBD length of > 12 mm was significant. CONCLUSION: A careful review of RPBD anatomy especially in patient with long RBD and caution when using the anterior Glissonian sheath approach might be helpful to prevent RPBDS during AS or CBS.

Metastable hexagonal close-packed palladium hydride in liquid cell TEM.

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

Single-port robot plus one port (SP + 1) distal pancreatectomy using the new da Vinci SP system.

PURPOSE: Single-incision laparoscopic distal pancreatectomy has not been widely applied due to technical challenges and increased operative risks. The newly released da Vinci SP system has been introduced to overcome these limitations and offer improvements for established robotic single-site procedures. We report our experience of robotic single port plus one port distal pancreatectomy using the da Vinci SP system. METHODS: We performed robotic distal pancreatectomy in three patients using the da Vinci SP surgical system with one additional port used for applying the energy device and stapling. Technical and clinical feasibility were examined. RESULTS: The mean age and body mass index were 70.7 years and 27.8 kg/m2, respectively. The mean operation time was 215 min. The estimated blood loss was less than 500 mL. All patients underwent combined splenectomy. The postoperative course of all patients was uneventful. CONCLUSION: Robotic distal pancreatectomy using the da Vinci SP system is safe and feasible, with acceptable perioperative outcomes.

Efficacy and Safety of Hepatitis B Virus Vaccination Following Hepatitis B Immunoglobulin Withdrawal After Liver Transplantation.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) and oral nucleoside/nucleotide analogs have been the mainstay of hepatitis B virus (HBV) prophylaxis after liver transplantation. However, long-term HBIG administration could have disadvantages, such as an increase in medical costs and the development of mutant HBV strains. This study aimed to investigate the safety and efficacy of HBV vaccination after the withdrawal of HBIG after liver transplantation. METHODS: This prospective open-label single-arm observational clinical trial enrolled 41 patients who underwent liver transplantation between 2010 and 2016 because of a condition related to chronic HBV infection. At the time of enrollment, all patients had taken entecavir and discontinued HBIG administration. When hepatitis B surface antibody titer was undetectable after the withdrawal of HBIG, a recombinant HBV vaccine was injected intramuscularly at month 0, 1, and 6. RESULTS: After excluding 5 patients who dropped out and 2 patients who had a persistent hepatitis B surface antibody titer, 9 (26.5%) of 34 patients had a positive vaccination response. The median hepatitis B surface antibody titer at seroconversion was 86 (12-1000) IU/L, and those at the end of follow-up were 216 (30-1000) IU/L. No patients experienced HBV recurrence during the study period. Sex (female, odds ratio 32.91 [1.83-592.54], P = .018) and the dosing interval of HBIG before withdrawal (≥90 days, 16.21 [1.21-217.31], P = .035) were independent contributing factors for positive response to the vaccination. CONCLUSION: HBV vaccination still deserves consideration as active immunoprophylaxis after liver transplantation because it could provide added immunity to nucleoside/nucleotide analogs monotherapy with excellent cost-effectiveness.

Portal modulation effects of terlipressin on liver regeneration and survival in a porcine model subjected to 90% hepatectomy.

BACKGROUND: Excessive postoperative portal pressure is associated with post-hepatectomy liver failure and small-for-size syndrome after partial liver transplantation. This study aimed to identify the portal modulation effects of terlipressin on liver regeneration and survival in a porcine model subjected to 90% hepatectomy. METHODS: Twenty pigs undergoing 90% hepatectomy were divided into control (n = 10) and terlipressin (n = 10) groups. Terlipressin 0.5 mg was injected subcutaneously three times a day, from immediately before hepatectomy to 7 days after surgery, for surviving pigs in the terlipressin group. Portal pressure measurement, biochemical analysis, assessment of molecular markers for liver regeneration, and immunohistochemistry were performed in both groups. RESULTS: The 7-day survival rate was significantly higher in the terlipressin group than that in the control group. Portal pressure in the terlipressin group was lower than that in the control group at 30 min and 1 h after hepatectomy. Total bilirubin level was lower in the terlipressin group than that in the control group at 1 h and 6 h after hepatectomy. Proliferating cell nuclear antigen expression was higher in the control group than that in the terlipressin group at 6 h after hepatectomy, while the proportion of Ki-67-positive cells was higher in the terlipressin group than that in the control group at 7 days after hepatectomy. Endothelin-1 level reflecting liver injury was lower in the terlipressin group than that in the control group at 1 h and 6 h after hepatectomy. CONCLUSION: Terlipressin could optimize liver regeneration and improve survival through rapid and effective portal modulation after extensive hepatectomy.

The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model.

BACKGROUND: Excessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery, contributing to developing post-hepatectomy liver failure. This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism, using a 70% hepatectomy porcine model. METHODS: Eighteen pigs undergoing 70% hepatectomy were involved in this study and divided into three groups: control (n=6), terlipressin (n=6), and octreotide (n=6). Terlipressin (0.5 mg) and octreotide (0.2 mg) were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day, at which time the surviving pigs were sacrificed. During the period, portal pressure, liver weight, biochemical analysis, histological injury score, and molecular markers were evaluated and compared between groups. RESULTS: The 7-day survival rates in the octreotide, terlipressin, and control groups were 100%, 83.3%, and 66.7%, respectively. The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes, 1 hour and 6 hours after hepatectomy. The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group (117% vs. 129%, P=0.03). Serum aspartate aminotransferase (AST) and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio (PT/INR) at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group. Serum endothelin-1 (ET-1) was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy (P<0.01). The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day (P<0.01). CONCLUSIONS: Splanchnic vasoactive agents, such as terlipressin and octreotide, could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.

Lipidomic signatures of post-hepatectomy liver failure using porcine hepatectomy models.

BACKGROUND: Clinical diagnosis of post-hepatectomy liver failure (PHLF) can only be made on or after the 5th postoperative day. Biomarker for early diagnosis is considered as a critical unmet need. METHODS: Twenty domestic female crossbreed (Yorkshire-landrace and duroc) pigs underwent sham operation (n=6), 70% (n=7) and 90% (n=7) partial hepatectomy (PH). A comprehensive lipidomic analysis was conducted using sera collected at pre-operation (PO), 14, 30, and 48 h after PH using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Of the 184 quantified lipids, 14 lipids showed significant differences between the two resection groups starting at 30 h after surgery. Four phosphatidylcholine (PC) plasmalogen species (P-16:0/16:0, P-18:0/18:2, P-18:0/20:4, and P-18:0/22:6) and PC 32:2 significantly increased in the 90% PH group while these returned to PO level after 30 h in the 70% PH group, presumably implying the failure markers. In contrast, eight triacylglycerol (TG) species (40:0, 42:1, 42:0, 44:1, 44:2, 46:1, 46:2, and 48:3) and sphingomyelin d18:1/20:0 showed an opposite trend, wherein they significantly decreased in the 90% PH group while these in the 70% PH group were abruptly increased until 30 h but returned to near PO levels at 48 h, implying the recovery markers. Same trends could also be observed in the level of whole lipid classes of PC plasmalogens and TGs, in addition to selected individual lipid species. CONCLUSIONS: Characteristic lipidomic signatures of PHLF could be identified using large animal models. These candidates have a potential to serve as a tool for early diagnosis and may open new paths to the study to overcome PHLF.