Nomogram based on lymphocyte-associated inflammatory indexes predicts portal vein thrombosis after splenectomy with esophagogastric devascularization.

OBJECTIVE: The relationship between lymphocyte-associated inflammatory indices and portal vein thrombosis (PVT) following splenectomy combined with esophagogastric devascularization (SED) is currently unclear. This study aims to investigate the association between these inflammatory indices and PVT, and to develop a nomogram based on these indices to predict the risk of PVT after SED, providing an early warning tool for clinical practice. METHODS: We conducted a retrospective analysis of clinical data from 131 cirrhotic patients who underwent SED at Lanzhou University's Second Hospital between January 2014 and January 2024. Independent risk factors for PVT were identified through univariate and multivariate logistic regression analyses, and the best variables were selected using the Akaike Information Criterion (AIC) to construct the nomogram. The model's predictive performance was assessed through receiver operating characteristic (ROC), calibration, decision, and clinical impact curves, with bootstrap resampling used for internal validation. RESULTS: The final model incorporated five variables: splenic vein diameter (SVD), D-Dimer, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and red cell distribution width-to-lymphocyte ratio (RLR), achieving an area under the curve (AUC) of 0.807, demonstrating high predictive accuracy. Calibration and decision curves demonstrated good calibration and significant clinical benefits. The model exhibited good stability through internal validation. CONCLUSION: The nomogram model based on lymphocyte-associated inflammatory indices effectively predicts the risk of portal vein thrombosis after SED, demonstrating high accuracy and clinical utility. Further validation in larger, multicenter studies is needed.

Effect of factor VIII and FVIII/PC ratio on portal vein thrombosis in liver cirrhosis: a systematic review and meta­analysis.

BACKGROUND: To date, there is an ongoing debate regarding the ability to predict PVT development using markers of FVIII or FVIII/PC ratio. This study presents evidence-based medical findings on the influence of FVIII activity levels and FVIII/PC values in the formation of PVT in cirrhosis. METHODS: The search for original studies on risk factors for portal vein thrombosis (PVT) associated with cirrhosis was conducted, which primarily focused on comparing circulating FVIII activity levels or FVIII/PC ratio in cirrhotic patients with and without PVT. The quality of evidence from each study was assessed using the Newcastle-Ottawa Scale. RESULTS: The meta-analysis included a total of 10 original studies. In total, 2250 cirrhotic patients were included, with 414 having PVT and 1836 without PVT. The pooled analysis using a random-effects model showed no significant difference in standardized mean difference (SMD) for FVIII activity levels in cirrhotic patients with or without PVT (SMD = 0.12, 95% CI=-0.46 to 0.70, P = 0.68), but there was significant heterogeneity (I2 = 95.52%, P = 0.00). Meta-regression analysis indicated that differences in mean FVIII activity levels in the PVT group, the number of cases in the non-PVT group, and the study design methods partially contributed to the heterogeneity (P < 0.05). However, compared to the non-PVT group, the PVT group had higher FVIII/PC ratio with a statistically significant difference (SMD = 0.39, 95% CI: 0.15 to 0.63, P = 0.00), and there was no significant heterogeneity (I2 = 28.62%). CONCLUSION: In conclusion, the FVIII/PC ratio not only reflects the severity of liver disease, but also can be used as one of the predictors of PVT development.

Therapeutic efficacy and in vivo distribution of human umbilical cord-derived mesenchymal stem cell spheroids transplanted via B-Ultrasound-guided percutaneous portal vein puncture in rhesus monkey models of liver fibrosis.

BACKGROUND: Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. METHODS: In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. RESULTS: We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-ß1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. CONCLUSIONS: This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

Efficacy of hepatic arterial infusion chemotherapy in patients with primary liver cancer with portal vein tumor thrombosis: a comparative analysis of different perfusion chemotherapeutic regimens.

BACKGROUND: Portal vein tumor thrombosis (PVTT) commonly occurs in patients with primary liver cancer (PLC). Transarterial chemoembolization (TACE) is a treatment for patients with PLC and PVTT. Some studies have shown that combining TACE therapy with hepatic arterial infusion chemotherapy (HAIC) might improve the survival rate of PLC patients with PVTT. However, few studies have compared the different regimens of PLC with PVTT. We aimed to compare the differences between the oxaliplatin + raltetrexed regimen and FOLFOX regimen. METHODS: We divided the 248 patients into two groups. There were 60 patients in the oxaliplatin + ratitetrexed group and 74 patients in the FOLFOX group. The primary endpoints were OS and PFS. The secondary endpoints were ORR and adverse events. We used SPSS software, the Kaplan-Meier method, the t test, and the rank sum test to compare the differences between the two groups. RESULTS: The median OS was 10.82 months in the oxaliplatin + raltitrexed group and 8.67 months in the FOLFOX group. The median PFS time was greater in the oxaliplatin + raltitrexed group (10.0 months) than that in the FOLFOX group (7.1 months). The ORR was greater in the oxaliplatin + raltitrexed group than that in the FOLFOX group (18.3% vs. 13.5%; P = 0.445). The DCR in the oxaliplatin + raltitrexed group was higher than that in the FOLFOX group (70.0% vs. 64.8%; P = 0.529). However, in the subgroup analysis, the difference between them was more significant in the type II PVTT subgroup. The OS was 12.08 months in the oxaliplatin + raltitrexed group and 7.26 months in the FOLFOX group (P = 0.008). The PFS was 11.68 months in the oxaliplatin + raltitrexed group and 6.26 months in the FOLFOX group (P = 0.014). In the right branch of type II PVTT, the OS was 13.54 months in the oxaliplatin + raltitrexed group and 6.89 months in the FOLFOX group (P = 0.015), and the PFS was 13.35 months in the oxaliplatin + raltitrexed group and 6.27 months in the FOLFOX group (P = 0.030). The incidence of adverse reactions was similar between the two groups. CONCLUSIONS: Compared with the FOLFOX regimen, the oxaliplatin + raltitrexed chemoembolization regimen had longer OS, PFS time and ORR and DCR and it was safe and tolerable.

Assessing the predictive efficacy of noninvasive liver fibrosis indices and portal vein diameter in predicting esophageal variceal bleeding in patients with cirrhosis.

BACKGROUND: The objective of this study is to evaluate the diagnostic accuracy of noninvasive serum liver fibrosis markers and portal vein diameter (PVD) in predicting the occurrence of esophageal variceal bleeding (EVB) in patients with cirrhosis. METHODS: A cohort comprising 102 individuals diagnosed with cirrhosis was divided into two groups: the P group (without EVB) and the PE group (with EVB). We conducted a comprehensive analysis comparing various noninvasive serum liver fibrosis indices, the Child-Pugh classification, ratios of aspartate aminotransferase to alanine aminotransferase, aspartate aminotransferase to platelet ratio index, fibrosis index based on four factors (FIB-4), PVD, and spleen thickness (SPT) between these groups. Receiver operating characteristic (ROC) curves were constructed for variables showing significant differences between the two groups, with subsequent calculation of the area under the ROC curve (AUROC) for each variable. RESULTS: Significant distinctions were noted in the serum liver fibrosis markers between the P and PE groups, encompassing hyaluronic acid (HA), type III procollagen (PC-III), type IV collagen (IV-C), PVD, SPT, and FIB-4 (p < 0.05), as evidenced by univariate analysis findings. The respective AUROC values for these markers were 0.653, 0.706, 0.710, 0.730, 0.660, and 0.633. Additionally, upon integration with PVD, SPT, and FIB4, the AUROC values for liver fibrosis markers surged to 0.793, 0.763, and 0.706 correspondingly, highlighting the enhanced diagnostic potential. CONCLUSION: The integration of noninvasive liver fibrosis indices and PVD showcased remarkable diagnostic potential in EVB, underscoring its clinical relevance in predicting hemorrhagic events.

Registration accuracy comparing different rendering techniques on local vs external virtual 3D liver model reconstruction for vascular landmark setting by intraoperative ultrasound in augmented reality navigated liver resection.

PURPOSE: Augmented reality navigation in liver surgery still faces technical challenges like insufficient registration accuracy. This study compared registration accuracy between local and external virtual 3D liver models (vir3DLivers) generated with different rendering techniques and the use of the left vs right main portal vein branch (LPV vs RPV) for landmark setting. The study should further examine how registration accuracy behaves with increasing distance from the ROI. METHODS: Retrospective registration accuracy analysis of an optical intraoperative 3D navigation system, used in 13 liver tumor patients undergoing liver resection/thermal ablation. RESULTS: 109 measurements in 13 patients were performed. Registration accuracy with local and external vir3DLivers was comparable (8.76 ± 0.9 mm vs 7.85 ± 0.9 mm; 95% CI = -0.73 to 2.55 mm; p = 0.272). Registrations via the LPV demonstrated significantly higher accuracy than via the RPV (6.2 ± 0.85 mm vs 10.41 ± 0.99 mm, 95% CI = 2.39 to 6.03 mm, p < 0.001). There was a statistically significant positive but weak correlation between the accuracy (dFeature) and the distance from the ROI (dROI) (r = 0.298; p = 0.002). CONCLUSION: Despite basing on different rendering techniques both local and external vir3DLivers have comparable registration accuracy, while LPV-based registrations significantly outperform RPV-based ones in accuracy. Higher accuracy can be assumed within distances of up to a few centimeters around the ROI.

Combined DeRitis ratio and alkaline phosphatase on the prediction of portal vein tumor thrombosis in patients with hepatocellular carcinoma.

Portal vein tumor thrombosis (PVTT) is one of the common complications of HCC and represents a sign of poor prognosis. PVTT signifies advanced liver cancer, deteriorating liver function, and heightened susceptibility to intrahepatic dissemination, systemic metastasis, and complications related to portal hypertension. It is important to seek novel strategies for PVTT arising from HCC. Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. This study aimed to investigate the diagnostic value of the combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) in predicting the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan-Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI 0.697-0.888). Based on the DALP classification (three scores: 0-2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR] 5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention.

Does portal vein anatomy influence intrahepatic distribution of metastases from colorectal cancer?

BACKGROUND: Other than location of the primary colorectal cancer (CRC), a few factors are known to influence the intrahepatic distribution of colorectal cancer liver metastases (CRLM). We aimed to assess whether the anatomy of the portal vein (PV) could influence the intrahepatic distribution of CRLM. PATIENTS AND METHODS: Patients with CRLM diagnosed between January 2018 and December 2022 at two tertiary centers were included and imaging was reviewed by two radiologists independently. Intra-operator concordance was assessed according to the intraclass correlation coefficient (ICC). The influence of the diameter, angulation of the PV branches and their variations on the number and distribution of CRLM were compared using Mann-Whitney, Kruskal-Wallis, Pearson's Chi-square and Spearman's correlation tests. RESULTS: Two hundred patients were included. ICC was high (> 0.90, P < 0.001). Intrahepatic CRLM distribution was right-liver, left-liver unilateral and bilateral in 66 (33%), 24 (12%) and 110 patients (55%), respectively. Median number of CRLM was 3 (1-7). Type 1, 2 and 3 portal vein variations were observed in 156 (78%), 19 (9.5%) and 25 (12%) patients, respectively. CRLM unilateral or bilateral distribution was not influenced by PV anatomical variations (P = 0.13), diameter of the right (P = 0.90) or left (P = 0.50) PV branches, angulation of the right (P = 0.20) or left (P = 0.80) PV branches and was independent from primary tumor localisation (P = 0.60). No correlations were found between CRLM number and diameter (R: 0.093, P = 0.10) or angulation of the PV branches (R: 0.012, P = 0.83). CONCLUSIONS: PV anatomy does not seem to influence the distribution and number of CRLM.

Efficacy of sorafenib plus transcatheter arterial chemoembolization in treating hepatocellular carcinoma with portal vein tumor thrombosis: A meta-analysis.

This meta-analysis aimed to evaluate the efficacy of sorafenib plus transcatheter arterial chemoembolization (TACE) in treating hepato-cellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Twelve randomized controlled trials published until 28th Sep 2022 were finally included. Of the total 1746 patients, of whom 458 received sorafenib and TACE treatment (Group S+TACE), and 1288 only underwent TACE (Group TACE), were enrolled. Outcomes including time to progression (TTP), objective response rate (ORR), disease control rate (DCR), overall survival (OS), survival rate (SR), and adverse reactions, were extracted. The OS (HR: 0.596, 95 %CI: 0.507-0.685, p < 0.001; I2 = 0.0 %) and TTP (HR: 0.379, 95 %CI: 0.205-0.553, p < 0.001; I2 = 4.5 %) in the S+TACE group were longer than those in the TACE group. The ORR (RR: 2.101, 95 %CI: 1.555-2.839, p < 0.001; I2 = 0.0 %), DCR (RR: 1.547, 95 %CI: 1.126-2.126, p = 0.007; I2 = 79.6 %) and SR (RR: 1.416, 95 %CI: 1.183-1.694, p < 0.001; I2 = 83.8 %) in the S+TACE group were higher than those in the TACE group. Compared with the TCAE group, the higher odds of HFSR, oral ulcer, and diarrhea among patients with HCC complicated by PVTT were discovered in the S+TACE group. The marginal significance was found in ascites and gastrointestinal bleeding between the two groups. Sorafenib plus TACE has good efficacy and mild adverse reactions, which may be worthy of clinical promotion.

[Portal vein embolization prior to major hepatectomy: A multidisciplinary approach for advanced liver tumors in Chile]. / Embolización portal previo a hepatectomía mayor: Experiencia multidisciplinaria en tumores hepáticos avanzados en Chile.

BACKGROUND: One of the main limitations to achieving a complete tumor resection in patients with technically resectable liver tumors is the presence of a small future liver remnant (FLR). Portal vein embolization (PVE) allows hypertrophy of the non-embolized lobe, reducing the risk of postoperative liver failure. AIM: To describe the experience of portal embolization prior to hepatectomy and its effectiveness in converting advanced unresectable liver tumors into resectable tumors. METHODS: Non-concurrent cohort study. All patients who underwent PVE before hepatectomy between 2016 and 2020 in our center were included. Demographic and diagnostic variables, pre and post-PVE volumes, perioperative variables, and global and disease-free survival were analyzed. RESULTS: Nineteen patients were included. Median age 66 (54-72) years and 57.9% (n= 11) were women. Bilateral metastases were present in 78.9% (n= 15). Sixteen patients (84.2%) received neoadjuvant chemotherapy. One patient (5.3%) had a complication after PVE. The median time between embolization and volumetry was 5.3 weeks (4.7-7.1). Median FLR before and after PVE were 19.8% (16.2-27.7) and 30% (25.2-40.5), respectively. The median percentage of hypertrophy was 48% (40.4-76.5). Fifteen patients (78.9%) underwent hepatectomy. Significant complications occurred in 26.6% (n= 4); among them, three patients (20%) presented postoperative liver failure. CONCLUSIONS: PVE is safe and effective in promoting FLR hypertrophy in the presence of chemotherapy, allowing patients with advanced liver tumors to undergo surgery with curative intent.

Natural history of spontaneous pancreatic portal vein fistulae: A systematic review of the literature.

BACKGROUND: Spontaneous pancreatic portal vein fistula (PPVF) - a rare complication of pancreatic inflammation - varies widely in presentation and means of diagnosis but has been previously associated with bleeding complications and mortality. A systematic review of published literature was performed to assess the frequency of outcomes. METHODS: A search of electronic databases (PubMed, Ovid MEDLINE, Scopus, EMBASE, gray literature) resulted in 1667 relevant unique manuscripts; 52 met inclusion criteria. RESULTS: A total of 74 unique (male n = 47, 63.5 %) patients were included. Mean age was 53.5 (±11.9) years. History of alcohol use was reported in 55 (74.3 %). Underlying chronic pancreatitis (CP) was present in 49 (66.2 %). In cases where presenting symptoms were reported (n = 57, 77.4 %), the most frequent were abdominal pain (63.5 %), weight loss (14.9 %), rash (12.2 %), nausea/vomiting (12.2 %), and polyarthritis (9.5 %). Computed tomography was the most common imaging modality used to confirm the diagnosis (n = 20, 27.0 %), followed by magnetic resonance cholangiopancreatography (n = 14, 18.9 %). Portal vein thrombosis was reported in 57 (77.0 %), and bleeding events (luminal, variceal, or intra-pseudocyst) were reported in 13(17.6 %) patients. Younger age was associated with higher risk of bleeding events. Mortality was reported in 12 (16.2 %) patients at any time during follow up. Older age and polyarthritis at presentation were associated with mortality. CONCLUSIONS: PPVF is a rare and potentially fatal condition, though rates of bleeding complication and death were relatively low in this population. High-quality observational studies are needed to better understand the pathophysiology and natural history of this diagnosis.

Tract embolization with gelatin sponge after percutaneous transhepatic portal vein intervention.

BACKGROUND: Bleeding from the puncture tract after percutaneous transhepatic portal vein intervention can become life-threatening. To date, studies about tract embolization with gelatin sponge after percutaneous transhepatic portal vein intervention are only with small numbers of patients, or non-consecutive or pediatric patients with a relatively small sheath in diameter. PURPOSE: To evaluate the safety and efficacy of tract embolization with gelatin sponge strips after percutaneous transhepatic poral vein access. MATERIAL AND METHODS: Between September 2017 and February 2024, 100 consecutive patients (61 men, 39 women; mean age = 53 ± 15 years) underwent a total of 105 portal vein interventions using a percutaneous transhepatic approach. Tract embolization for the removal of 6-8 Fr sheath was performed using gelatin sponge strips in all procedures, including 71 portal vein embolization before major hepatectomy, 27 portal balloon venoplasty or stent placement after liver transplantation, and seven other interventions. RESULTS: No bleeding occurred after tract embolization with gelatin sponge strips. Minor portal vein thrombosis was detected in three procedures after liver transplantation and in one procedure for portal vein stenosis caused by essential thrombocytopenia. Thrombosis occurred in the punctured portal vein branch in all procedures. Thrombosis was not clinically relevant in any patient, and it was difficult to differentiate whether thrombosis was caused by sheath placement or the inserted gelatin sponge. CONCLUSION: Tract embolization with gelatin sponge strips after percutaneous transhepatic portal vein intervention is a safe and feasible method for preventing hemorrhage from the puncture tract.

Peri-operative Anticoagulation Strategies, Bleeding and Thrombotic Complications in Pediatric Patients Undergoing Intervention for Congenital Portosystemic Shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications. METHODS: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications. RESULTS: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported. CONCLUSIONS: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively. LEVELS OF EVIDENCE: Level II, retrospective study.

Is reoperation required for patients presenting with hepatic portal venous gas after gastrointestinal surgery: a review of the literature.

BACKGROUND AND OBJECTIVE: Hepatic portal venous gas(HPVG) represents a rare radiographic phenomenon frequently linked to intestinal necrosis, historically deemed to need immediate surgical intervention. The pivotal query arises about the imperative of urgent surgery when a patient manifests HPVG after gastrointestinal surgery. This inquiry seeks to elucidate whether emergent surgical measures remain a requisite in such cases. METHODS: The investigation into 14 cases of HPVG after gastrointestinal procedures was conducted through a comprehensive review of relevant literature. This methodological approach contributes to a nuanced understanding of HPVG occurrences following gastrointestinal surgery, informing clinical considerations and potential therapeutic strategies. RESULTS: Among the 14 patients, 12 recovered and 2 died. 6 patients underwent surgical exploration, 4 with negative findings and recovered. 8 cases received conservative treatment, resulting in improvement for 5, and 1 initially treated conservatively, revealed perforation during later surgical exploration, leading to improvement, 1 case ended in mortality. CONCLUSION: After gastrointestinal surgery, in Computed Tomography (CT) imaging, the coexistence of HPVG and gastrointestinal dilatation, without signs of peritoneal irritation on abdominal examination, may suggest HPVG due to acute gastrointestinal injury, intestinal gas, and displacement of gas-producing bacteria. These patients can be managed conservatively under close supervision. In cases where HPVG coexists with gastrointestinal dilatation and Pneumatosis intestinalis (PI) without signs of peritoneal irritation, conservative treatment may be continued under close supervision. However, if progressive exacerbation occurs despite close monitoring and the aforementioned treatments, timely surgical exploration is deemed necessary. When HPVG is combined with signs of peritoneal irritation, prompt laparotomy and exploration are preferred.

The Effect of Ascorbic Acid on Hepatic Ischaemia-Reperfusion Injury in Wistar Rats: An Experimental Study.

Liver ischaemia-reperfusion (IR) during hepatic surgeries can lead to liver cell death via oxidative stress and the activation of immune cells, the release of cytokines, and damage-associated molecular patterns. Ascorbic acid has been shown to confer potential protective effects against IR injury, mainly due to its antioxidant properties. This study evaluated the effect of ascorbic acid infusion at different time points during hepatic IR in rats. Thirty-six male Wistar rats were divided into control and experimental groups that received the same total ascorbic acid dose at three different infusion times: before ischaemia, before reperfusion, or before both ischaemia and reperfusion. All of the animals experienced hepatic IR injury. We measured the hepatic enzymes, cytokines, and portal blood flow. Animals receiving ascorbic acid before both ischaemia and reperfusion had lower liver enzyme levels, reduced inflammation, and better portal venous flow than other animals. Divided doses of ascorbic acid before IR may be beneficial for reducing liver injury associated with IR.

GSDMD-Dependent Neutrophil Extracellular Traps Mediate Portal Vein Thrombosis and Associated Fibrosis in Cirrhosis.

Portal vein thrombosis (PVT) is a challenging and controversial complication of cirrhosis. Experimental models that reproduce cirrhotic PVT and effective pharmacological therapies are limited. We aimed to investigate the nature course and mechanisms of PVT in cirrhosis. A novel PVT model was developed via two-step total portal vein ligation in healthy and thioacetamide (TAA)-cirrhotic rats. Circulating and liver-infiltrating neutrophils were isolated from individuals with cirrhosis to examine neutrophil extracellular traps (NETs) and explore their unique characteristics and implications in PVT-associated fibrosis in cirrhosis. We further validated macrophage-myofibroblast transition (MMT) via multiplex immunofluorescence and single-cell sequencing. In the experimental model, cirrhosis promoted PVT development and portal vein intimal thickening. Interestingly, cirrhosis promoted spontaneous resolution of PVT due to instability of thrombus structure, along with pulmonary and intrahepatic clots. NETs-MMT mediate cirrhotic PVT and PVT-associated fibrosis, including fibrotic thrombus remodeling and increased hepatic collagen deposition. Mechanistically, caspase-4-dependent activation of neutrophils and GSDMD mediated the formation of NETs. The extracellular DNA of NETs promoted TGF-ß1/Smad3-driven MMT. Inhibiting GSDMD with disulfiram suppressed cirrhotic PVT and prevented associated fibrosis. The cirrhotic PVT model reflected the following three main characteristics of cirrhotic PVT: spontaneous resolution, immunothrombosis, and intimal fibrosis. Targeting NETs with GSDMD inhibitors may serve as a new therapeutic concept to treat cirrhotic PVT.