Lobe Of Liver Research Articles

Evaluating preoperative coagulation panels in dogs undergoing liver lobectomy for primary liver tumors: A multi-institutional retrospective study.

The objectives of this study were to: (i) Determine whether operable primary liver tumors were associated with prolongations in prothrombin time (PT) and activated partial thromboplastin time (aPTT) and (ii) determine if these secondary hemostatic abnormalities were more prevalent with specific liver tumors. Multi-institutional retrospective study. Dogs (n = 359) undergoing liver lobectomy for a primary liver tumor with a preoperative coagulation panel. Data was identified via electronic medical record review at eight veterinary teaching hospitals. Baseline dog characteristics, coagulation panel values, platelet count, emergency versus non-emergency procedure, whether the dogs received transfusion(s) of a blood product, liver lobe removed, and histopathological diagnosis were extracted from the medical record. Chi-square analysis was used to compare categorical variables between groups. Continuous variables were assessed for normality using the Shapiro-Wilk test. A total of 74 of 359 dogs (20.6%) had a prolongation in either PT or aPTT preoperatively. A total of 20 of 359 dogs (5.6%) were found to have prolongation of both PT and aPTT. Hemangiosarcoma was the only histopathological diagnosis associated with concurrent prolongations of both PT and aPTT (p < .001) in 6/16 (37.5%) dogs. Coagulation panels including PT and aPTT are unlikely to detect substantial deficiencies in secondary hemostasis in most dogs with primary liver tumors except in dogs with a histopathological diagnosis of hemangiosarcoma. PT and aPTT testing is low yield as an elective preoperative screening test in dogs with primary liver tumors except in dogs where there is a hemoabdomen or high suspicion for hepatic hemangiosarcoma.

Right liver lobe diameter to serum albumin ratio and blood ammonia level as non-invasive predictor for the presence of esophageal varices and the risk of bleeding in patient of cirrhosis of liver

Right liver lobe diameter to serum albumin ratio and blood ammonia level as non-invasive predictor for the presence of esophageal varices and the risk of bleeding in patient of cirrhosis of liver

Development Postnatal of the Kidney and Liver in Albino Rat Rattus Rattus, Histological and Biochemical Study

Objective: The primary goal of the current study was to look at histological, histochemical, and biochemical aspects of the development structure of rat's kidney and liver. Materials and Method: Seventy eight samples of kidney and liver were obtained from rats at days; 1, 5, 10, 15, 36 and 90 after birth and processed for histological, histochemical and biochemical techniques. Results: Up to the fifth day, new nephron anlages develop in the renal cortex. After ten days, the final anlages form into functional nephrons, and fifteen days after the corticis forms, the cortex seems mature. The collecting ducts and loops of Henle expand longitudinally to form the renal medulla. The immature medulla is structurally similar to the later inner stripe of the outer zone and cannot be split into distinct zones. Within ten days, the inner zone was developed, and within fifteen days, the outside zone's stripe. The kidney tubule's diameter increased with age, the renal medulla was mature at 36 days, the kidney was covered in a moderate amount of collagen fiber, and the henle loops were lengthy at certain ages, but short at adult age. Adults had larger corpuscle and nephron lumens. In contrast, the thick renal capsule at other ages contained less collagen fibers. A tiny renal gap encircling the glomeruli and a notably greater quantity of fibers were visible in adult Bowman's capsules. The liver was encased in a thin capsule on the first day of birth and a thick capsule between 36 and 90 days later. On day 15, the cells surrounding the central veins began to arrange themselves in a regular fashion. The hepatic parenchyma could be seen by symmetrical hepatic cords, which emerged from the central veins as radiating columns. After five days, Von Kuffer cells began to line the sinusoids next to the endothelial cells. On the tenth day, the hepatic sinusoids took on a more regular appearance, stretching between the hepatic cords and joining the central veins. The hepatic lobules with their central vein were visible at the age of 15 days. The capsule then thickened and elastic fibers started to show up. The reticular fibers also thickened and spread, and in 36 days, collagen fibers started to show up in the portal areas. Based on histochemical data, every PAS, AB, and PAS-AB stain was highly reacted with brush in renal and hepatic cells. In conclusion: The kidney and liver developed differently after birth and reached their mature, typical structures in 36 days.

Biomimetic Liver Lobules from Multi-Compartmental Microfluidics.

Engineered liver lobule is highly practical in hepatic disease treatment, while constructing a 3D biomimetic lobule with a heterogeneous architecture on a large scale is challenging. Here, inspired by the natural architectural construction of hepatic lobules, biomimetic hepatic lobules are proposed with coaxially through-pores for nutrient exchange via microfluidic technology. This multi-channel microfluidic chip is made by parallelly installing capillaries. Sodium alginate (Alg) is pumped through its central channel, while Ca2+-loaded gelatin methacrylate (GelMA) solutions encapsulating hepatocytes, mesenchymal stem cells, and endothelia cells are pumped through surrounding channels, respectively. The rapid gelation of Alg and Ca2+ brings about an in situ formation of Alg fiber, with heterogeneous multi-cell-laden GelMA microcarriers forming around it. The peeled-off microcarriers each featured with a coaxially through pore, simulating the cord-like structure of hepatic lobule and facilitating nutrients exchange. Meanwhile, the spatially anisotropic arrangement of cells highly simulates the hepatic architecture. It is demonstrated that by transplanting these biomimetic microparticles into liver in situ, the failed liver in rat shows increased regeneration and decreased necrosis. These results indicated that the microfluidic multi-compartmental microcarriers provide a new strategy to engineer 3D artificial livers for clinical translation.

Pharmaceutical Interventions for the Management of Hemorrhagic Shock in Hepatic Surgery: An Experimental Swine Model Outcome.

Introduction During abdominal trauma or major hepatic surgery, the liver can be subjected to hypoxic conditions due to hemorrhage, leading to various degrees of ischemic injury to hepatocytes. Hemorrhagic shock, a critical and life-threatening condition, often complicates hepatic surgery due to massive blood loss, resulting in inadequate tissue perfusion and oxygenation. The challenge in managing hemorrhagic shock in hepatic surgery is heightened by the liver's unique blood supply and its crucial role in coagulation. Effective treatment requires a multifaceted approach, including surgical intervention, blood transfusions, and pharmaceutical therapy to stabilize hemodynamics and promote coagulation. Additionally, reperfusion of the liver after resuscitation can cause severe injury through inflammatory and oxidative pathways, potentially leading to multiple organ dysfunction. This study examines the effectiveness of combining standard fluid therapy with antioxidants (bucillamine and valproic acid) in mitigating oxidative stress and reducing hepatocyte damage in the context of hemorrhagic shock. Method Thirty male swine were randomly divided into four groups as follows: Group A (n=6/control group), Group B (n=8), Group C (n=8), and Group D (n=8). A resection of the left liver lobe was performed, followed by the controlled loss of a specific volume of blood until the mean arterial pressure dropped to between 30 and 40 mmHg. The animals were maintained in this state of hypovolemic shock for 50 minutes, followed by IV administration of fluids. Additionally, pharmaceutical agents were administered to Groups B (bucillamine), C (valproic acid), and D (combination of bucillamine and valproic acid). The experiment lasted six hours in total. Results The study showed that animals treated with pharmaceutical agents like bucillamine and valproic acid and their combination demonstrated significantly reduced serum levels of protein carbonyls (PCs) and thiobarbituric acid reactive substances (TBARS) compared to the control group. Furthermore, histological evaluation of liver tissues revealed that treated animals showed reduced histopathological signs of injury, suggesting that the pharmaceutical agents not only lowered biochemical markers of oxidative stress but also provided a protective effect against liver damage in the context of hemorrhagic shock. Conclusion These findings suggest that incorporating antioxidant therapy into resuscitation protocols may offer substantial benefits in mitigating hepatic damage associated with hemorrhagic shock. This approach could potentially improve outcomes in clinical settings where oxidative stress plays a critical role in injury progression by better understanding the pathophysiology of this complex and dynamic process.

Relevance of lesion size in navigator-triggered and free-breathing diffusion-weighted liver MRI.

The purpose of this study was to investigate the relevance of focal liver lesions (FLL) size for lesion detection comparing navigator triggering (TRIG) to free breathing (FB) liver Diffusion-weighted magnetic resonance imaging (DWI). Patients with known or suspected FLL were prospectively (registry number 276_19 B) included from October to December 2019 in this study, out of which 32 had liver lesions. Echo planar spin-echo DWI data both with TRIG and FB were with approximately constant acquisition times acquired at 1.5 T. Lesions were segmented in the b = 800 s/mm² images in both the TRIG and FB images. The lesion size, location (liver segment), liver lesion visibility, as well as contrast-to-noise ratio (CNR) were recorded. The CNR was assessed with the Wilcoxon-Mann-Whitney test and the number of visible lesions with the Fisher test. Data from 43 patients (22 female) were analyzed. The mean patient age was 58 ± 14 years. A total of 885 FLL (Ntotal) were segmented. Among these, 811 lesions (Nboth) were detected with TRIG and FB, 65 lesions exclusively with TRIG (NTRIG_Only), and nine exclusively in FB (NFB_Only). The largest additional lesion in TRIG/FB had a diameter of 10.4 mm/7.6 mm. The number of additional lesions detected with TRIG decreased with size. Among all lesions ≤ 4.7 mm, the relative number of additional lesions was 15.6%. Additional lesions were found in all liver segments with TRIG. In the left liver lobe, the relative proportion was 9.2%, and in the right liver lobe 5.4%. CNR and visibility were significantly higher in TRIG than in FB (p < 0.001). In relation to size, the difference is significant in terms of visibility and CNR for lesion diameters ≤ 8 mm. Respiration triggering can improve the detection of small liver lesions with diameters up to approx. 1 cm in the whole liver. Question Can respiration triggering (TRIG) improve the detection of small FLL compared to FB diffusion-weighted imaging? Findings Among 885 segmented FLL, TRIG was superior to FB for lesions smaller than 8 mm and had improved CNR and visibility. Clinical relevance Diffusion-weighted magnetic resonance imaging is used for the detection of focal liver lesions and image quality is influenced by breathing motion. Navigator triggering becomes more important for smaller lesions, and seems recommendable for the detection of small focal liver lesions.

PSXII-19 Influence of dietary copper concentration and liver sampling location on liver copper concentrations in three breeds (Gulf Coast Native, Suffolk x Hampshire, and Jacob) of sheep

Abstract Male sheep (n = 27) from three different breeds: 1) Gulf Coast Native (GCN; n = 9 wethers), 2) Suffolk x Hampshire (SHC; n = 9 wethers), and 3) Jacob (JCB; n = 9 intact males) approximately 9 mo of age, [body weight (BW) = 38.16 ± 2.43 kg) were stratified by BW and breed into 3 treatment groups to examine the impact of breed, supplemental copper (Cu) dose, and liver sampling location on liver Cu concentrations. On d 0 of the experiment, liver biopsies were collected from 5 sheep per breed and analyzed for Cu concentrations. Animals were housed in individual pens and received 2% of BW of a pelleted concentrate containing the appropriate Cu treatment once daily and hay in amounts to allow ad libitum access to hay over a 24 h period. Treatments consisted of 1) low Cu (LCu; 15.3 mg Cu/kg DM), 2) moderate Cu (MCu; 17.7 mg Cu/kg DM), and 3) high Cu (HCu; 23.8 mg Cu/kg DM) from CuSO4∙5H2O. On d 50 of the experiment, all animals were weighed and transported to an USDA inspected abattoir and harvested. Following harvest, samples were obtained from the left and right lobes of the liver and thoroughly washed with phosphate-buffered saline. All liver samples were dried, ashed, and reconstituted in 5 mL of 1.2 N HCl for Cu analysis. Data were analyzed as a randomized block design using the MIXED procedure in SAS with individual animal as the experimental unit. There was a three-way interaction between breed x treatment x liver lobe (P &amp;lt; 0.04). The right liver lobe in HCu JCB sheep had greater (P &amp;lt; 0.05) Cu concentrations compared with the left liver lobe. Both the left and right lobes of the liver had greater (P &amp;lt; 0.001) Cu concentrations compared with the initial liver Cu concentration in MCu JCB sheep. The right liver lobe of HCu GCN sheep tended (P &amp;lt; 0.07) to have greater liver Cu concentrations compared with the left liver lobe. The Cu concentration in the right liver lobe tended (P &amp;lt; 0.09) to be greater in MCu sheep compared with the left liver lobe. Liver Cu concentrations within the right lobe of HCu GCN sheep were greater (P &amp;lt; 0.05) than liver Cu concentrations in the right and left liver lobe samples in LCu GCN sheep. Liver Cu concentrations in SHC sheep were not influenced by treatment. Future research examining the impact of breed and Cu supplementation on the molecular mechanisms associated with Cu absorption, storage, and excretion is warranted.

PSLBI-5 Ruminal papillae morphology of beef on dairy heifers with abscessed or non-abscessed livers

Abstract The ruminal papillae morphology characteristics of feedlot beef on dairy non-spayed heifers with liver abscess to those with non-abscessed liver were evaluated. Heifers were sourced from 27 lots which were harvested on six dates between November 2022 and February 2023. Upon harvest, a total of 94 rumen tissue samples from animals presenting liver abscesses and 110 rumen tissue samples from animals with non-abscessed livers were collected in pairs, as abscesses were identified within the harvesting facility viscera inspection line, following a randomized complete block design (block = lot within harvest date). Individual fragments (6 cm2) from the cranial sac epithelium of the rumen were collected, rinsed with deionized water, immersed in 70% alcohol, and preserved under refrigeration (4 oC) until analysis. Ruminal tissues were trimmed (1 cm2), in which the number of papillae was counted by three trained personnel, followed by the removal of 12 representative papillae specimens for further area electronic scanning (The University of Texas Health Science Center of San Antonio, Image Tool) to determine average papillae area, number per cm2 (AVP), average papillae area in cm2 (APA), absorptive surface area in cm2/fragment cm2 (ASA), and papillae absorptive surface area, % (ASA). Data were analyzed using the GLIMMIX procedures of SAS, with individual animal ruminal tissue used as the experimental unit, the fixed effect of ruminal condition, and the random effect of lot within the harvesting date. Average papillae number (P = 0.27), average papillae area (P = 0.74), absorptive surface area (P = 0.48), and papillae absorptive surface area (P = 0.43) were not affected by the presence of liver abscess. Severity of liver abscess distinguished as A -, A, or A+ scores compared with non-abscessed liver showed no difference on papillae number (P = 0.34), papillae area (P = 0.89), and absorptive area (P = 0.62). The presence of small or large liver abscesses did not affect the papillae area, size, or absorptive area (P ≥ 0.41). The liver lobe location of abscesses (cranial, caudal, both) did not affect (P ≥ 0.17) any of the ruminal morphological variables measured. The presence of liver abscesses, whether diffuse or localized, in beef on dairy heifers, did not affect (P ≥ 0.58) the development of ruminal papillae. The presence, severity, or location of liver abscess was not connected with ruminal papillae number, area, or absorptive surface area of beef on dairy heifers measured upon harvest time. The absence of ruminal papillae morphological changes in animals committed with liver abscesses may be further investigated with the characterization of potential cellular physical changes of the ruminal tissue and the integrity of the primary barrier in the digestive tract.

An unusual cause of liver neoplasm in an older female.

We presented a 66-year-old woman with T2DM who had a liver mass discovered incidentally during hospitalization. She was asymptomatic with a right upper abdominal mass that was smooth, mobile, and non-tender. Hepatitis virus markers and tumor markers were normal. The computed tomography (CT) images showed a 4.7×4.0 cm lesion in the left liver lobe with indistinct borders. Further magnetic resonance imaging (MRI) revealed low T1 and high T2 signal intensity with ring-shaped enhancement following contrast administration. Surgical resection was performed, and histology confirmed hepatic angioleiomyoma with thick-walled vessels and spindle cell proliferation. Immunohistochemistry was positive for SMA, desmin, caldesmon, CD31, and CD34. The patient had no recurrence during 5 years follow-up.

Liver segmental volumes and their relationship with 5-year prognostication.

This study aimed to analyze the predictive value of caudate to right lobe ratio (CRL-R) and liver segmental volume ratio (LSVR) for chronic liver disease (CLD) on routine abdominal CT scans and their association with 5-year decompensation- and transplant-free survival. This retrospective study included 108 patients without CLD and 98 patients with biopsy-proven CLD. All patients underwent abdominal CT scans between 03/2015 and 08/2017. Patients with CLD were divided into three groups: early CLD (F0-F2; eCLD; n = 40), advanced CLD (F3-F4; aCLD; n = 20), and aCLD with clinically significant portal hypertension (aCLDPH; n = 38). CRL-R and LSVR were compared between groups using Kruskal-Wallis test and ROC analysis to determine cutoff-values. 5-year decompensation- and transplant-free survival were assessed by Kaplan-Meier curve analysis. CRL-R and LSVR were significantly different between all groups (p < 0.001). A CRL-R cutoff-value of > 0.99 predicted aCLD with a sensitivity of 69% and a specificity of 80% (AUC = 0.75, p < 0.001), while LSVR > 0.37 had a sensitivity of 67% and a specificity of 84% (AUC = 0.80, p < 0.001). CLD-patients with both CRL-R > 0.99 and LSVR > 0.37 had a significantly lower probability of 5-year decompensation-free survival (31%) as well as lower probability of 5-year transplant-free survival (41%) than those with a CRL-R < 0.99 and/or LSVR < 0.37 (70%, 62%, p = 0.006, p = 0.038). CRL-R and LSVR showed a high predictive value for CLD on routine abdominal CT scans. In patients with CLD, both CRL-R and LSVR may be combined and are associated with 5-year decompensation-free and transplant-free survival.

Multidepth quantitative analysis of liver cell viscoelastic properties: Fusion of nanoindentation and finite element modeling techniques.

Liver cells are the basic functional unit of the liver. However, repeated or sustained injury leads to structural disorders of liver lobules, proliferation of fibrous tissue and changes in structure, thus increasing scar tissue. Cellular fibrosis affects tissue stiffness, shear force, and other cellular mechanical forces. Mechanical force characteristics can serve as important indicators of cell damage and cirrhosis. Atomic force microscopy (AFM) has been widely used to study cell surface mechanics. However, characterization of the deep mechanical properties inside liver cells remains an underdeveloped field. In this work, cell nanoindentation was combined with finite element analysis to simulate and analyze the mechanical responses of liver cells at different depths in vitro and their internal responses and stress diffusion distributions after being subjected to normal stress. The sensitivities of the visco-hyperelastic parameters of the finite element model to the effects of the peak force and equilibrium force were compared. The force curves of alcohol-damaged liver cells at different depths were measured and compared with those of undamaged liver cells. The inverse analysis method was used to simulate the finite element model in vitro. Changes in the parameters of the cell model after injury were explored and analyzed, and their potential for characterizing hepatocellular injury and related treatments was evaluated. RESEARCH HIGHLIGHTS: This study aims to establish an in vitro hyperelastic model of liver cells and analyze the mechanical changes of cells in vitro. An analysis method combining finite element analysis model and nanoindentation was used to obtain the key parameters of the model. The multi-depth mechanical differences and internal structural changes of injured liver cells were analyzed.

Agenesis of Left Hepatic Lobe: A Rare Congenital Anomaly. Case Report

Morphologic anomalies of the liver, as opposed to many other visceral organs, are very rare. Left lobe liver agenesis is defined as the absence of liver tissue on the left side of the liver in the absence of previous disease or surgery. It is commonly an accidental finding on imaging investigations or at the time of abdominal surgery. We report the case of left liver lobe agenesis diagnosed in a 68-year-old man with a history of urothelial carcinoma of the bladder, and the diagnosis of his liver congenital abnormality was made accidentally on a CT of chest-abdomen-pelvis (initially done to look for secondary localisations of his urothelial carcinoma). The main imaging findings of this condition are reviewed briefly, with associations and the most common differential diagnoses.

Digital quantitation of bridging fibrosis and septa reveals changes in natural history and treatment not seen with conventional histology.

Metabolic dysfunction-associated steatohepatitis (MASH) with bridging fibrosis is a critical stage in the evolution of fatty liver disease. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence (AI) provides sensitive and reproducible quantitation of liver fibrosis. This methodology was applied to gain an in-depth understanding of intra-stage fibrosis changes and septa analyses in a homogenous, well-characterised group with MASH F3 fibrosis. Paired liver biopsies (baseline [BL] and end of treatment [EOT]) of 57 patients (placebo, n = 17 and tropifexor n = 40), with F3 fibrosis stage at BL according to the clinical research network (CRN) scoring, were included. Unstained sections were examined using SHG/TPEF microscopy with AI. Changes in liver fibrosis overall and in five areas of liver lobules were quantitatively assessed by qFibrosis. Progressive, regressive septa, and 12 septa parameters were quantitatively analysed. qFibrosis demonstrated fibrosis progression or regression in 14/17 (82%) patients receiving placebo, while the CRN scoring categorised 11/17 (65%) as 'no change'. Radar maps with qFibrosis readouts visualised quantitative fibrosis dynamics in different areas of liver lobules even in cases categorised as 'No Change'. Measurement of septa parameters objectively differentiated regressive and progressive septa (p < .001). Quantitative changes in individual septa parameters (BL to EOT) were observed both in the 'no change' and the 'regression' subgroups, as defined by the CRN scoring. SHG/TPEF microscopy with AI provides greater granularity and precision in assessing fibrosis dynamics in patients with bridging fibrosis, thus advancing knowledge development of fibrosis evolution in natural history and in clinical trials.

Hepatic Sinusoidal Disorders.

Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.

Clinically significant portal hypertension in patients with primary biliary cholangitis: Clinicopathological features and prognostic value

Introduction and ObjectivesPrimary biliary cholangitis (PBC) may progress to clinically significant portal hypertension (CSPH) before the development of cirrhosis. This study aimed to investigate CSPH incidence as well as the clinicopathological characteristics and predictive value of these features for the prognosis of patients with PBC, especially at early histologic stage. Patients and MethodsPatients diagnosed with PBC between January 2013 and April 2022 were retrospectively enrolled. The prognostic value of baseline clinicopathological characteristics for long-term outcomes in PBC patients with CSPH was assessed using Kaplan–Meier survival analysis and COX regression analysis. ResultsAmong 280 patients with PBC, 104 underwent liver biopsy and 68 were at early histologic stage. CSPH was present in 47.2 % of participants with 20.6 % at early histologic stage. CSPH was a risk factor for predicting the liver transplant-free survival in PBC patients (hazard ratio [HR], 6.78; 95 % CI, 2.94–15.63), especially those at early stage. Perisinusoidal fibrosis and nodular regenerative hyperplasia (NRH) were common histopathological features in PBC patients with CSPH at the early stages. Fibrous septa formation in the hepatic lobules (HR, 4.85; 95 % CI, 1.51–15.52) and cholestasis (HR, 7.70; 95 % CI, 2.56–23.18) were independent predictors of adverse outcomes. ConclusionsCSPH indicates an increased risk of adverse outcomes in PBC patients, especially those in early histologic stage. Perisinusoidal fibrosis and NRH are valuable histological features of CSPH in patients with early-stage PBC. Identification of clinicopathological features and assessment of portal hypertension (especially at early stage), contribute to the development of personalized strategies.

S21-04 A microphysiological system of the liver that recapitulates the cellular composition and organization of the hepatic lobule

S21-04 A microphysiological system of the liver that recapitulates the cellular composition and organization of the hepatic lobule

Hepatocyte aquaporin 8-mediated water transport facilitates bile dilution and prevents gallstone formation in mice

Although water channel aquaporin-8 (AQP8) has been implicated in hepatic bile formation and liver diseases associated with abnormal bile flow in human and animal studies, direct evidence of its involvement in bile secretion is still lacking. This study aimed to determine the role of AQP8 in bile secretion and gallstone formation. We generated various transgenic knock-in and knockout mouse models and assessed liver AQP8 expression by immunostaining and immunoblotting, hepatic bile secretion by cannulation of the common bile duct, cholesterol gallstone formation by feeding a high-fat lithogenic diet, and identified regulatory small molecules by screening the organic fractions of cholagogic Chinese herbs and biochemical characterization. We identified a novel expression pattern of AQP8 protein in the canalicular membrane of approximately 50% of the liver lobules. AQP8-deficient mice exhibited impaired hepatic bile formation, characterized by the secretion of concentrated bile with a lower flow rate and higher levels of bile lipids than that of wild-type littermates. AQP8-/- mice showed accelerated gallstone formation, which was rescued by AAV-mediated hepatic expression of AQP8 or AQP1. Moreover, we identified a small molecule, scutellarin, that upregulates hepatocyte AQP8 expression in vitro and in vivo. In AQP8+/+ mice, scutellarin significantly increased bile flow, decreased bile lipid concentrations, and prevented gallstone formation compared to AQP8-/- mice. Molecular studies revealed that scutellarin promoted the ubiquitination and degradation of HIF-1α, a transcriptional negative regulator of AQP8, by disrupting its interactions with HSP90. AQP8 plays a crucial role in facilitating water transport and bile dilution during hepatic bile formation, thereby mitigating gallstone formation in mice. Small-molecule intervention validated hepatocyte AQP8 as a promising drug target for gallstone therapy. The incidence of gallstone disease is high, and current drug treatments for gallstones are very limited, necessitating the identification of novel drug targets for developing new drugs with universal applicability. To our knowledge, this is the first study to provide direct evidence that hepatic water channel AQP8 plays a key role in bile dilution and gallstone formation. Modulation of hepatic water transport may provide a universal therapeutic strategy for all types of gallstone diseases.

Do We Need a Relaparotomy to Remove the Perihepatic Packs Used to Control Bleeding? Case Series

Introduction: Liver injuries, often resulting from trauma, present a significant challenge in surgical management. Perihepatic packing has emerged as a critical technique in controlling bleeding and stabilising patients with severe liver injuries. This study aims to evaluate the outcomes of perihepatic packing and removing packs without relaparotomy in a cohort of eleven patients treated over two years.Methods: We conducted a retrospective study of 11 patients with liver injuries identified at laparotomy at General Hospital Kuliyapitiya from May 2020 to June 2022. Excluded were patients who managed without packing. Data were collected from operating theatre records and medical charts, including age, sex, injury mechanism, vital signs, FAST scan results, intraoperative findings, estimated blood loss, blood transfused in the first 24 hours, associated injuries, liver complications, time to pack removal, and incidence of rebleeding.Perihepatic packing has been used for persistent hepatic haemorrhage post-suturing, unsaturable injuries, and hemodynamically unstable patients. Packs have been brought outside the abdomen through a separate incision and sutured to each other if multiple packs were used. A G28 intercostal tube has placed for drainage. Packs have been removed between 48 and 72 hours. The drain has kept for more than 48 hours post-removal to monitor rebleeding. In cases of uncontrollable haemorrhage during pack removal, plans included reopening and repacking if necessary.Results: The study included eleven patients aged 24 to 74 years, with three female patients. The causes of liver injuries were identified as follows: road traffic accidents (63.6%), assault (18.2%), stab injuries (9.1%), and falls from height (9.1%). Pre-operative ultrasound correctly identified liver injuries in 54.6% of patients. Intraoperative findings showed right liver lobe involvement in 63.6% of cases, bilobar involvement in 27.3%, and left lobe involvement in 9.1%. Additionally, 63.6% of patients had other organ injuries. The timing of pack removal was within 48 hours for seven patients (63.6%) and within 48-72 hours for the remaining patients. Drains were removed on the fifth day in 54.50% of patients and on the sixth day in the rest. There were no cases of rebleeding and post of complications were able to be managed conservatively. There was one death with sepsis and multi organ disfunction.Conclusion: Perihepatic packing is a valuable technique in the management of liver injuries, demonstrating high efficacy in controlling haemorrhage and low complication rates. Removal of the pack through the pre-placed incision avoids the relaparotomy and thereby reduces the second trauma to the patient. Further studies with larger cohorts are recommended to validate these findings.

PE074 Robotic Spiegel lobe liver resection with thrombectomy for level II-IV inferior vena cava thrombus: A safe technique for better control of the retrohepatic IVC

PE074 Robotic Spiegel lobe liver resection with thrombectomy for level II-IV inferior vena cava thrombus: A safe technique for better control of the retrohepatic IVC

Comparative analysis of hepatic fat quantification across 5 T, 3 T and 1.5 T: A study on consistency and feasibility

ObjectivesMagnetic resonance imaging (MRI) is a critical noninvasive technique for evaluating liver steatosis, with efficient and precise fat quantification being essential for diagnosing liver diseases. This study leverages 5 T ultra-high-field MRI to demonstrate the clinical significance of liver fat quantification, and explores the consistency and accuracy of the Proton Density Fat Fraction (PDFF) in the liver across different magnetic field strengths and measurement methodologies. MethodsThe study involved phantoms with lipid contents ranging from 0 % to 30 % and 35 participants (21 females, 14 males; average age 30.17 ± 13.98 years, body mass index 25.84 ± 4.76, waist-hip ratio 0.84 ± 0.09). PDFF measurements were conducted using chemical shift encoded (CSE) MRI at 5 T, 3 T, and 1.5 T, alongside magnetic resonance spectroscopy (MRS) at 5 T and 1.5 T for both liver and phantoms, analyzed using jMRUI software. The MRS-derived PDFF values served as the reference standard. Repeatability of 5 T MRI measurements was assessed through correlation analysis, while accuracy was evaluated using linear regression analysis against the reference standards. ResultsThe CSE-PDFF measurements at 5 T demonstrated strong consistency with those at 3 T and 1.5 T, showing high intraclass correlation coefficients (ICC) of 0.988 and 0.980, respectively (all p < 0.001). There was also significant consistency across ROIs within liver lobes, with ICC values ranging from 0.975 to 0.986 (all p < 0.001). MRS-PDFF measurements for both phantoms and liver at 5 T and 1.5 T exhibited substantial agreement, with ICC values of 0.996 and 0.980, respectively (all p < 0.001). Particularly, ICC values for ROIs in the liver ranged from 0.963 to 0.990 (all p < 0.001). Despite overall agreement, statistically significant differences were noted in specific ROIs within the liver lobes (p = 0.004 and 0.012). The CSE and MRS PDFF measurements at 5 T displayed strong consistency, with an ICC of 0.988 (p < 0.001), and significant agreement was also found between 5 T CSE and 1.5 T MRS PDFF measurements, with an ICC of 0.978 (p < 0.001). Agreement was significant within the ROIs of the liver lobes on the same platform at 5 T, with ICC values ranging from 0.986 to 0.991 (all p < 0.001). ConclusionPDFF measurements at 5 T MR imaging exhibited both accuracy and repeatability, indicating that 5 T imaging provides reliable quantification of liver fat content and shows substantial potential for clinical diagnostic applications.