Portal Vein Research Articles

Derivation of Splenic Stiffness in Subjects with Normal Liver Stiffness and No Vascular Liver Disease Using Transient Elastography with a Spleen-Dedicated Module: A Large Cross Sectional Study.

Liver and splenic stiffness measurements (LSM and SSM) are useful to predict varices and clinical decompensation in cirrhosis. SSM values are highly variable and overlapping and no guidelines exists on what constitutes normal SSM, that might limit interpretation of results. Consecutive subjects with LSM < 6 kPa and reliable SSM (FibroScan630 Expert device with spleen-dedicated module) and no vascular liver disease were analysed for significant correlations of SSM values with age, sex, BMI, portal and splenic vein diameter, splenic diameter, liver fat and diabetes. Based on timeline of SSM, subjects were randomly assigned in 70:30 ratio into derivation [n = 502] and validation subset [n = 214]. Of 7200 subjects with simultaneous reliable LSM and SSM, 715 fulfilled the selection criteria (mean age: 43.8 ± 12.8years, 67.2% male, mean BMI-26.4 ± 4.5kg/m2). The mean SSM was 22.6 ± 5.8kPa (c10-c90 percentile range: 15.2-31.3kPa) and followed the normal distribution curve. In the derivation subset, mean SSM for males was higher than female (23.06 ± 6.2vs. 21.78 ± 5.93kPa; p = 0.028). SSM value correlated with LSM (r = 0.454, p = 0.001). Mean SSM in subjects with LSM 3-4, 4.1-5 and 5.1-6kPa were 21.7 ± 5.8, 22.27 ± 5.67and 23.76 ± 5.88kPa (p value = 0.001). There was no difference in SSM based on age, BMI, diabetes and liver fat on ultrasound. Above results hold true for subjects in validation subset. SSM range in subjects with normal LSM and no vascular liver disease using spleen-dedicated module varies from 15.2 to 31.3kPa, values being higher in male and not affected by Age, BMI, spleen size, liver fat and diabetes. Our results may serve as reference point in evaluation of SSM in compensated advanced liver disease patients.

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.

An initial report of robotic-assisted anatomical liver resection with indocyanine green fluorescence navigation using the ultrasound-guided preoperative positive staining technique.

Robotic-assisted surgery has become increasingly popular because of its potential benefits. Anatomical liver resection (ALR) is a valuable strategy in hepatocellular carcinoma (HCC) management. ALR with indocyanine green (ICG) fluorescence navigation was reported as an effective solution for segment identification. We reported a simple and convenient "preoperative positive staining technique" for laparoscopic ALR to overcome some limitations. To our knowledge, this is the first report of robotic-assisted surgery in which ALR was performed using this technique. A 69-year-old man presented with a 12-mm HCC in segment 8. Preoperative three-dimensional simulation images showed that the fourth-order branch of the portal vein was a tumor-bearing portal pedicle. After anesthesia induction, 1 mL of 0.025 mg/mL ICG was injected percutaneously into this branch under B-mode ultrasound guidance before pneumoperitoneum. A robotic laparoscope was inserted. The preoperative positive staining area was clearly stained on the liver surface with the Firefly mode on the da Vinci Xi system. Based on the demarcation line, the liver parenchymal resection was started. The ICG fluorescence staining area was checked frequently on the resected side of the liver transection plane. Subsequently, the fourth-order portal branch was identified with the ICG fluorescence technique and ligated. Finally, the specimen was resected. The operation took 352 min, with 10 mL of blood loss, and was completed without any operative problems. Although many cases are required, the proposed preoperative positive staining technique appears useful for accurate and precise surgery given the increasing application of robotic-assisted hepatectomy.

The Interplay between Severe Cirrhosis and Heart: A Focus on Diastolic Dysfunction.

Background/Objectives: Cardiovascular involvement in severe cirrhosis presents diagnostic challenges and carries significant prognostic implications. This study aims to evaluate the relationship between liver disease severity and portal hypertension with the burden of diastolic dysfunction. Methods: We prospectively enrolled patients with hepatic cirrhosis, classified according to the Child-Pugh criteria. Of the 102 patients included, 65 were classified as Group A (non-severe cirrhosis: Child-Pugh Classes A and B) and 37 as Group B (severe cirrhosis: Child-Pugh Class C). Portal vein and spleen diameters were assessed using abdominal ultrasound. All patients underwent echocardiographic evaluation. LV systolic function was assessed by measuring ejection fraction, while diastolic function was evaluated using three parameters: E/Em ratio, E/Vp ratio, and indexed left atrial volume. Results: We observed a significantly greater burden of diastolic dysfunction in Group B compared to Group A. Specifically, the E/Vp ratio was 2.2 ± 0.4 in Group B versus 1.9 ± 0.3 in Group A (p < 0.001); the indexed LA volume was 34.5 ± 3.2 mL/m2 in Group B versus 30.1 ± 2.9 mL/m2 in Group A (p < 0.001); and the E/Em ratio was 17.0 ± 3.0 in Group B versus 11.5 ± 2.8 in Group A (p < 0.001). Additionally, the mean diameters of the portal vein and spleen were larger in Group B, with measurements of 14.3 ± 2.1 mm versus 11.5 ± 1.6 mm for the portal vein and 15.0 ± 1.2 mm versus 11.7 ± 1.5 mm for the spleen (p < 0.001), which correlated with the extent of diastolic dysfunction. Conclusions: Diastolic dysfunction was prevalent in 55% of patients with liver cirrhosis. The burden of diastolic dysfunction was higher in patients with severe hepatic cirrhosis compared to those with milder forms, and it correlated with the severity of portal hypertension, as assessed by measuring portal vein diameter and spleen diameter.

321 Application of the Fick Principle for the study of visceral nutrient absorption and metabolism

Abstract In 1870, Adolf Fick introduced the concept for the calculation of cardiac output by measuring gas exchange in the lungs at a meeting of the Würzburg Physiology and Medical Society. It was not until around 1930 after the development of cardiac catheterization that it was fully verified. Fick’s equation also serves as the basis for all indicator dilution methods for measuring blood flow and has been applied to several tissues throughout the body. By measuring the blood concentration of nutrients supplying and draining a tissue bed, coupled with the flow of blood, the net nutrient exchange can be calculated. Researchers first began investigating the movement of nutrients into the portal system of ruminants in the 1950s and the first method for measuring nutrient exchange in small ruminants was published in the 1960s. This approach requires the implantation of vascular catheters into an artery and the hepatic portal vein which drains the stomach, intestines, and spleen. An additional catheter is implanted upstream in a mesenteric vein for infusion of a blood flow marker, and the addition of a catheter in a hepatic vein allows the measure of blood flow and nutrient transfer in the liver. These methods were adapted for calves and dairy cows in the 1970s. The 1980s brought further refinement of the methodologies such as improved catheter materials allowing animals to be maintained for extended periods and, several researchers published data from cattle, sheep, and goats. These methods have been coupled with measures of ruminal and intestinal disappearance as well as isotopic tracers to examine nutrient exchange and metabolism by tissues. The goal of this presentation is to review the development of this approach for studying nutrient absorption in vivo, and to highlight specific advancements in its application.

Portal Vein Pulsatility: A Valuable Approach for Monitoring Venous Congestion and Prognostic Evaluation in Acute Decompensated Heart Failure.

The severity of systemic congestion is associated with increased portal vein flow pulsatility (PVP). To determine the usefulness of PVP as a marker of decongestion and prognosis in acute decompensated heart failure (ADHF) patients. 105 patients, 60% of whom were men, were hospitalized with ADHF, and their PVP index (PVPI) was calculated (maximum velocity-minimum velocity/maximum velocity) × 100 on admission and before discharge, along with their EVEREST score, inferior vena cava diameter (IVC), NT-proBNP, serum sodium, and glomerular filtration rate. A PVPI ≥ 50% was defined as a marker of systemic congestion. After treatment with loop diuretics, a decrease in PVPI of >50% before discharge was considered a marker of decongestion The patients were classified into two groups (G): G1-PVPI decrease ≥ 50% (54 patients) and G2-PVPI decrease < 50% (51 patients). At discharge, compared to G2, G1 patients had lower mean PVPI (14.2 vs. 38.9; p < 0.001), higher serum Na (138 vs. 132 mmol/L, p = 0.03), and a higher number of patients with a significant (>30%) NT-proBNP decrease (42 vs. 27, p = 0.007). PVPI correlated with IVC (r = 0.55, p < 0.001), NT-proBNP (r = 0.21, p = 0.04), and serum Na (r = -0.202, p = 0.04). A total of 55% of patients had worsening renal failure (G1 63% vs. G2 48%, p = 0.17). After 90 days, G2 patients had higher mortality (27.45% vs. 3.7 p = 0.001) and rehospitalization (49.01% vs. 33.33%, p < 0.001). In multivariate regression analysis, PVPI was an independent predictor of rehospitalization (OR 1.05, 95% CI 1.00-1.10, p = 0.048). Portal vein flow pulsatility, a meaningful marker of persistent subclinical congestion, is related to short-term prognosis in ADHF patients.

Effect of sarcopenia on liver cirrhosis with complicating oesophageal and gastric varices after endoscopic therapy

Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4 %) was significantly lower than that in patients with LC-EGVB (41.2 %). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

A rare case of pancreatic pseudocyst-portal vein fistula in a patient with chronic pancreatitis.

A 60-year-old female with chronic pancreatitis and a history of splenectomy presented with epigastric pain, vomiting, and asthenia. Elevated pancreatic enzymes and CT imaging revealed a pseudocyst in the pancreatic head with suspected communication to the portal vein, confirmed by MR Cholangiopancreatography and endoscopic ultrasound (EUS). EUS-guided puncture revealed high amylase levels. Given her manageable symptoms, a conservative approach was adopted, leading to symptomatic relief and pseudocyst size reduction. Pancreatic pseudocyst-portal vein fistula is a rare pancreatitis complication, challenging to diagnose, with no gold-standard treatment. Endoscopic stenting offers a promising alternative to surgery for severe cases.

Pylorus-preserving pancreaticoduodenectomy with superior mesenteric vein resection and reconstruction in a child with recurrent hepatoblastoma after liver transplantation.

Pancreaticoduodenectomy with vascular reconstruction is rarely performed in children. We present a 3-year-old male with stage IV hepatoblastoma and pre-treatment extent of disease (PRETEXT) stage III with tumor into the portal vein and superior mesenteric vein (SMV), and with brain and lung metastases status post chemotherapy and stereotactic radiosurgery to left frontal brain lesion. He then underwent deceased donor liver transplant with Roux-en-Y hepaticojejunostomy complicated by two recurrences to bilateral lungs treated with wedge resections. His course lastly involved a third hepatoblastoma recurrence to the SMV that was managed with pylorus-preserving pancreaticoduodenectomy with SMV resection and reconstruction.

Performance evaluation of a 4D similarity filter for dynamic CT angiography imaging of the liver.

Dynamic computed tomography (CT) angiography of the abdomen provides perfusion information and characteristics of the tissues present in the abdomen. This information could potentially help characterize liver metastases. However, radiation dose has to be relatively low for the patient, causing the images to have very high noise content. Denoising methods are needed to increase image quality. The purpose of this study was to investigate the performance, limitations, and behavior of a new 4D filtering method, called the 4D Similarity Filter (4DSF), to reduce image noise in temporal CT data. The 4DSF averages voxels with similar time-intensity curves (TICs). Each phase is filtered individually using the information of all phases except for the one being filtered. This approach minimizes the bias toward the noise initially present in this phase. Since the 4DSF does not base similarity on spatial proximity, loss of spatial resolution is avoided. The 4DSF was evaluated on a 12-phase liver dynamic CT angiography acquisition of 52 digital anthropomorphic phantoms, each containing one hypervascular 1cm lesion with a small necrotic core. The metrics used for evaluation were noise reduction, lesion contrast-to-noise ratio (CNR), CT number accuracy using peak-time and peak-intensity of the TICs, and resolution loss. The results were compared to those obtained by the time-intensity profile similarity (TIPS) filter, which uses the whole TIC for determining similarity, and the combination 4DSF followed by TIPS filter (4DSF + TIPS). The 4DSF alone resulted in a median noise reduction by a factor of 6.8, which is lower than that obtained by the TIPS filter at 8.1, and 4DSF + TIPS at 12.2. The 4DSF increased the median CNR from 0. 44 to 1.85, which is less than the TIPS filter at 2.59 and 4DSF + TIPS at 3.12. However, the peak-intensity accuracy in the TICs was superior for the 4DSF, with a median intensity decrease of -34 HU compared to -88 and -50 HU for the hepatic artery when using the TIPS filter and 4DSF + TIPS, respectively. The median peak-time accuracy was inferior for the 4DSF filter and 4DSF + TIPS, with a time shift of -1 phases for the portal vein TIC compared to no shift in time when using the TIPS. The analysis of the full-width-at-half-maximum (FWHM) of a small artery showed significantly less spatial resolution loss for the 4DSF at 3.2 pixels, compared to the TIPS filter at 4.3 pixels, and 3.4 pixels for the 4DSF + TIPS. The 4DSF can reduce noise with almost no resolution loss, making the filter very suitable for denoising 4D CT data for detection tasks, even in very low dose, i.e., very high noise level, situations. In combination with the TIPS filter, the noise reduction can be increased even further.

A Monograph on Anatomy and Variants of Hepatic Resectional Surgery

BACKGROUND: The liver anatomy appears to be very complex due to the enormous number of vascular and biliary branches as well as the fact that the underlying pathology frequently distorts the anatomy. To prevent damage during surgical or invasive procedures, it is advised to be aware of the arteries’ typical structure and variations. Hepatic surgeons, general surgeons, transplant surgeons, interventional radiologists, and other medical specialists who treat liver problems must have this knowledge. MATERIALS AND METHODS: We have retrospectively evaluated the PubMed databases, Embase, and the Cochrane Library by applying various combinations of subject-related terms. The search terms identified with the medical subject heading were “Anatomy, right hepatectomy, resection, variants.” The databases were used to collect the literature published since 1991. RESULTS: Results delineated that 91.6% of patients had a single right hepatic vein, 81% shared a trunk with their middle hepatic vein (MHV) and left hepatic vein (LHV), and 19% had separate MHV and LHV drainage into the inferior vena cava. Overall prevalences of the abnormal hepatic artery, abnormal right hepatic artery (aRHA), abnormal left hepatic artery (aLHA), and combined aRHA/aLHA were found to be 27.41%, 15.63%, 16.32%, and 4.53%, respectively. The most common variation (type 2) is the so-called “portal vein (PV) trifurcation,” in which the main PV divides into the left PV, the right anterior PV, and the right posterior PV. The right posterior sectoral duct joins the left hepatic duct with a supraportal course, the right posterior sectoral duct joins the right anterior sectoral duct with an infraportal course, the trifurcation variation of the biliary tree, retroportal course, and the left lateral segmental ducts caudal to the umbilical portion of the PV are examples of variant biliary anatomy encountered in PV variations. Duplication of the common bile duct is a very uncommon congenital biliary system defect. CONCLUSION: It is very crucial for surgeon to have abreast knowledge of the tributaries, their anatomy, and variations to limit blood loss and operative morbidities.

The First Case of Intra-portal Islet Implantation During Liver Machine Perfusion Allowing Simultaneous Islet-liver Transplantation in A Human: A New and Safe Treatment for End-stage Liver Disease Combined With Diabetes Mellitus.

Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors: Where do we stand?

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival.

A case of resected anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor with literature review

BackgroundGranulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth.Case presentationA 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45.ConclusionsG-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods.

Comprehensive Review of Future Liver Remnant (FLR) Assessment and Hypertrophy Techniques Before Major Hepatectomy: How to Assess and Manage the FLR.

The regenerative capacities of the liver and improvements in surgical techniques have expanded the possibilities of resectability. Liver resection is often the only curative treatment for primary and secondary malignancies, despite the risk of post-hepatectomy liver failure (PHLF). This serious complication (with a 50% mortality rate) can be avoided by better assessment of liver volume and function of the future liver remnant (FLR). The aim of this review was to understand and assess clinical, biological, and imaging predictors of PHLF risk, as well as the various hypertrophy techniques, to achieve an adequate FLR before hepatectomy. We reviewed the state of the art in liver regeneration and FLR hypertrophy techniques. The use of new biological scores (such as the aspartate aminotransferase/platelet ratio index + albumin-bilirubin [APRI+ALBI] score), concurrent utilization of 99mTc-mebrofenin scintigraphy (HBS), or dynamic hepatocyte contrast-enhanced MRI (DHCE-MRI) for liver volumetry helps predict the risk of PHLF. Besides portal vein embolization, there are other FLR optimization techniques that have their indications in case of risk of failure (e.g., associating liver partition and portal vein ligation for staged hepatectomy, liver venous deprivation) or in specific situations (transarterial radioembolization). There is a need to standardize volumetry and function measurement techniques, as well as FLR hypertrophy techniques, to limit the risk of PHLF.

Deubiquitinase USP18 inhibits hepatic stellate cells activation and alleviates liver fibrosis via regulation of TAK1 activity

Background & aimsActivation of hepatic stellate cells (HSCs) is the key process underlying liver fibrosis. Unveiling its molecular mechanism may provide an effective target for inhibiting liver fibrosis. Protein ubiquitination is a dynamic and reversible process. Deubiquitinases (DUBs) catalyze the removal of ubiquitin chains from substrate proteins, thereby inhibiting the biological processes regulated by ubiquitination signals. However, there are few studies revealing the role of deubiquitination in the activation of HSCs. Methods & resultsSingle-cell RNA sequencing (scRNA-seq) revealed significantly decreased USP18 expression in activated HSCs when compared to quiescent HSCs. In mouse primary HSCs, continuous activation of HSCs led to a gradual decrease in USP18 expression whilst restoration of USP18 expression significantly inhibited HSC activation. Injection of USP18 lentivirus into the portal vein of a CCl4-induced liver fibrosis mouse model confirmed that overexpression of USP18 can significantly reduce the degree of liver fibrosis. In terms of mechanism, we screened some targets of USP18 in mouse primary HSCs and found that USP18 could directly bind to TAK1. Furthermore, we demonstrated that USP18 can inhibit TAK1 activity by interfering with the K63 ubiquitination of TAK1. ConclusionsOur study demonstrated that USP18 inhibited HSC activation and alleviated liver fibrosis via modulation of TAK1 activity; this may prove to be an effective target for inhibiting liver fibrosis.

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

PurposeAugmented 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.MethodsRetrospective registration accuracy analysis of an optical intraoperative 3D navigation system, used in 13 liver tumor patients undergoing liver resection/thermal ablation.Results109 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).ConclusionDespite 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.

Transfemoral hepatic vein access in double vein embolization – initial experience and feasibility

BackgroundHepatic vein embolization in double vein embolization (DVE) can be performed with transhepatic, transjugular or transfemoral access. This study evaluates the feasibility and technical success of using a transfemoral access for the hepatic vein embolization in patients undergoing preoperative to induce hypertrophy of the future liver remnant (FLR).Material and methodsRetrospective analysis of single center cohort including 17 consecutive patients. The baseline standardized FLR was 18.2% (range 14.7–24.9). Portal vein embolization was performed with vascular plugs and glue through an ipsilateral transhepatic access. Hepatic vein embolization was performed using vascular plugs. Access for the hepatic vein was either transhepatic, transjugular or transfemoral. Technical success, number of hepatic veins embolized and complications were registered. In addition, volumetric data including degree of hypertrophy (DH) and kinetic growth rate (KGR), and resection data were registered.R: Seven of the 17 patients had transfemoral hepatic vein embolization, with 100% technical success. No severe complications were registered. In the whole cohort, the median number of hepatic veins embolized was 2 (1–6). DH was 8.6% (3.0–19.4) and KGR was 3.6%/week (1.4–7.4), without significant differences between the patients having transfemoral versus transhepatic /transjugular access (p = 0.48 and 0.54 respectively). Time from DVE to surgery was median 4.8 weeks (2.6–33.9) for the whole cohort, with one patient declining surgery, two having explorative laparotomy and one patient having change of surgical strategy due to insufficient growth.ConclusionTransfemoral access is a feasible option with a high degree of technical success for hepatic vein embolization in patients with small future liver remnants needing DVE.

An orally administered glucose-responsive polymeric complex for high-efficiency and safe delivery of insulin in mice and pigs.

Contrary to current insulin formulations, endogenous insulin has direct access to the portal vein, regulating glucose metabolism in the liver with minimal hypoglycaemia. Here we report the synthesis of an amphiphilic diblock copolymer comprising a glucose-responsive positively charged segment and polycarboxybetaine. The mixing of this polymer with insulin facilitates the formation of worm-like micelles, achieving highly efficient absorption by the gastrointestinal tract and the creation of a glucose-responsive reservoir in the liver. Under hyperglycaemic conditions, the polymer triggers a rapid release of insulin, establishing a portal-to-peripheral insulin gradient-similarly to endogenous insulin-for the safe regulation of blood glucose. This insulin formulation exhibits a dose-dependent blood-glucose-regulating effect in a streptozotocin-induced mouse model of type 1 diabetes and controls the blood glucose at normoglycaemia for one day in non-obese diabetic mice. In addition, the formulation demonstrates a blood-glucose-lowering effect for one day in a pig model of type 1 diabetes without observable hypoglycaemia, showing promise for the safe and effective management of type 1 diabetes.

Boosting impacts of Acacia nilotica against hepatic toxicity induced by gentamicin: biochemical, anti-inflammatory and immunohistochemical study.

It seems that gentamicin's toxicity to the liver is caused by reactive oxygen species production. The antioxidant and anti-inflammatory properties of Acacia nilotica extract (AN) have been demonstrated in recent studies. This research focused on how AN's extract affected gentamicin-induced liver damage in rats. Twenty-four Wister rats of male type were divided into four groups: first group received saline as a control, second group received AN (5%) for fifteen days, group three received daily intraperitoneal injections of gentamicin (100mg/kg) for fifteen days, and group four, as mentioned in groups 2 and 3, also received gentamicin injections and AN extraction (5%) for fifteen days. In order to conduct biochemical analysis, serum was extracted. Histopathology, immunohistochemistry analyses for hepatic toxicity were all performed on the collected tissue samples. Serum levels of ALT, AST, total bilirubin, and GGT were all elevated after using gentamicin. The inflammatory cytokines)IL-1, TNF-α and IL-6(, all were increased in gentamycin-injected group. There were showing deformity of bile duct, hepatocellular necrosis and infiltration of inflammatory cells congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area (white arrows), hypertrophy in gentamycin-injected group compared to AN plus gentamycin administered rats. There were upregulation in the immunoreactivity of COX-2, IFNkB and TGF-beta1 (TGF-β1) in gentamycin intoxicated rats. When gentamicin and AN were administered together, hepatic biomarkers, inflammatory cytokines, histological, and immunohistochemical markers were all ameliorated by AN administration.