Portal Vein Research Articles

A real-world drug safety surveillance study of lenvatinib from the FAERS database

ABSTRACT Background There is a need to determine lenvatinib-associated real-world adverse events (AEs) as its adverse effects may result in its discontinuation. Research design and methods Lenvatinib-associated AEs were analyzed and quantified and risk signals from the first quarter of 2015 to the fourth quarter of 2023 were detected through data mining. Potential targets for lenvatinib-associated cholecystitis, cholangitis, and hepatic encephalopathy were identified by data mining. Result 68 Preferred Terms (PTs) with an important imbalance were kept. Unexpected AEs, such as immune-mediated hepatitis, portal vein thrombosis and adrenal insufficiency were associated with the use of lenvatinib use. Lenvatinib alone was more strongly associated with adrenal insufficiency than lenvatinib and pembrolizumab combination. Hepatic encephalopathy was more strongly correlated with drug use when Lenvatinib was administered to male patients with hepatocellular carcinoma. Most AEs occurred during the first month after treatment, with a median onset time of 41 days. FGFR4, PDGFRA, and KIT (Lenvatinib targets) are potentially linked to cholecystitis, cholangitis, and hepatic encephalopathy. Conclusions We identified Lenvatinib-associated AEs and discovered new AEs that will be useful for clinical monitoring and risk assessment.

Lipopolysaccharide, arbiter of the gut-liver axis, modulates hepatic cell pathophysiology in alcoholism.

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of the outer membrane of gram-negative bacteria-is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut-liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut-liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut-liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

Portal vein stenting blocked the inflow tract and completely resolved bile duct varices, formed by cavernous transformation of the portal vein.

There is no established treatment for bleeding bile duct varices (BDVs). We report the first case of portal vein (PV) stenting completely eradicating bleeding BDVs. A 70-year-old male with malignant lymphoma developed BDVs due to PV obstruction, which had caused compression and stricture of the distal bile duct. Endoscopic retrograde cholangiography was performed to evaluate the stricture and bleeding from the ruptured BDV was observed. Endoscopic hemostasis was difficult, requiring reopening of the extra-hepatic PV and reducing the blood flow to the BDVs for hemostasis. Therefore, PV stenting was performed. During the procedure, portal angiography confirmed an inflow tract to the BDVs. Therefore, covered stents were placed in the PV and adjusted to block the inflow tract to the BDVs at the distal end. After stenting, the BDVs were successfully blocked and all PV blood flowed through the stent placed in the extra-hepatic PV. Two weeks after stenting, the BDVs had disappeared completely and the bleeding has not recurred for months. We experienced a case in which PV stenting not only reopened an obstructed PV but also successfully occluded the inflow tract. This case demonstrates the potential of PV stenting for the treatment of hemorrhagic BDVs.

COVID-19-Related Cholangiopathy: Histological Findings.

We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51-60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390-1256); GGT 925 (664-2169); ALT 100 (86-113); AST 87 (68-106); and bilirubin 4 (1-9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150-249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.

Clinical predictive factors of the efficacy of immune checkpoint inhibitors and kinase inhibitors in advanced hepatocellular cancer.

Hepatocellular carcinoma (HCC) is a highly aggressive tumor associated with significant morbidity and mortality rates. Combination therapy with immune checkpoint inhibitors (ICIs) and kinase inhibitors has emerged as a promising strategy for liver cancer treatment in recent years. However, the clinical factors predicting the outcomes of combination therapy in patients with advanced liver cancer remain uncertain. Therefore, this study investigated the relationships between clinical predictors and the efficacy of ICI plus kinase inhibitor therapy to personalize treatment plans. We retrospectively enrolled 98 patients who received combination treatment with ICIs and kinase inhibitors for advanced HCC. Based on blood lipid levels and other clinical factors prior to treatment, we investigated potential biomarkers that could predict treatment responses in this patient population. Mean progression-free survival (PFS) and overall survival (OS) in this cohort were 10.1 and 17.2months, respectively. Via multivariate analysis, the absence of extrahepatic metastasis, the absence of portal vein thrombosis (PVT), neutrophil-to-lymphocyte ratio (NLR) < 3.225, platelet-to-lymphocyte ratio (PLR) < 140.75, and prognostic nutritional index (PNI) ≥ 37.25 were identified as independent predictors of improved PFS. Factors associated with better OS included PLR < 140.75 and total cholesterol (TC) < 3.46mmol/L. Univariate analysis identified significant associations of Eastern Cooperative Oncology Group performance status (ECOG PS), hepatitis B virus (HBV) DNA levels, Child-Pugh classification, alpha-fetoprotein (AFP), TC, and the receipt of regorafenib with PFS. Additionally, ECOG PS, Child-Pugh classification, AFP, PVT, NLR, PNI, and the receipt of regorafenib were significantly associated with OS. PLR and TC were potential clinical predictive factors for survival outcomes in patients with advanced HCC who received ICI/kinase inhibitor combination therapy. It is important to know the clinical characteristics of patients prior to treatment initiation to optimize outcomes.

Identification of microbial antigens in liver tissues involved in the pathogenesis of primary biliary cholangitis using 16S rRNA metagenome analysis.

Multiple factors are involved in the pathogenesis of primary biliary cholangitis (PBC), a chronic cholestatic liver disease, characterized by intrahepatic cholangiopathy. In particular, studies have suggested that environmental factors such as the presence of granulomas in the portal vein region are important for the development of PBC. This study aimed to comprehensively analyze and identify foreign-derived antigens in PBC liver tissue to confirm their involvement in PBC pathogenesis. Portal areas and hepatocyte regions were selectively dissected from formalin-fixed paraffin-embedded PBC liver tissue samples using the microlaser method, followed by total DNA extraction. We then validated whether the bacterial strains identified through 16S rRNA metagenomic analysis were detected in PBC liver tissues. The most frequently detected bacterial genera in the PBC liver tissue samples were Sphingomonas panacis, Providencia, and Cutibacterium. These bacterial genera were also detected in the other PBC samples. Validation for the detection of S. panacis, the most abundant genus, revealed polymerase chain reaction bands extracted from the portal areas of all samples. They were also more highly expressed than bands detected in the hepatocyte region. S. panacis antigen was specifically detected in the portal areas of PBC liver tissues. The introduction of foreign-derived antigens into the liver as an environmental factor could be a possible mechanism for the development of PBC.

Local and Systemic Micro-Rheological Changes during Intestinal Anastomosis Operation: A Metabolic Dependence in an Experimental Model.

Hemorheological factors may show arterio-venous differences. Alterations in acid-base and metabolic parameters may also influence these factors. However, little is known about changes in micro-rheological parameters during abdominal surgery, influencing splanchnic circulation. In anesthetized pigs, the external jugular vein, femoral artery and vein were cannulated unilaterally, and paramedian laparotomy was performed. In the anastomosis group, after resecting a bowel segment, end-to-end jejuno-jejunostomy was completed. Blood samples (from cannulas and by puncturing the portal vein) were taken before and after the intervention. Hematological, acid-base and blood gas parameters, metabolites, red blood cell (RBC) deformability and aggregation were determined. The highest hematocrit was found in portal blood, increasing further by the end of operation. A significant pH decrease was seen, and portal blood showed the highest lactate and creatinine concentration. The highest RBC aggregation values were found in arterial, the lowest in renal venous blood. The RBC aggregation increased with higher lactate concentration and lower pH. Osmotic gradient deformability declined, with the lowest values in portal and renal venous samples. In conclusion, micro-rheological parameters showed arterio-venous and porto-renal venous differences, influenced by oxygenation level, pH and lactate concentration. The intestinal anastomosis operation caused an immediate micro-rheological deterioration with portal venous dominancy in this experiment.

Successful pancreatectomy after conversion-intended chemotherapy using gemcitabine and nab-paclitaxel for unresectable adenosquamous carcinoma of the pancreas: a case report

BackgroundAdenosquamous carcinoma of the pancreas (ASCP) accounts for only 1–4% of all pancreatic exocrine cancers and has a particularly poor prognosis. The efficacy of chemotherapy for ASCP remains unknown because of the small number of cases, and few studies have evaluated conversion-intended chemotherapy.Case presentationA 76-year-old woman was referred to our hospital because of epigastric pain and nausea. A preoperative contrast-enhanced multidetector row computed tomography (MDCT) scan revealed a 17 × 17 mm low-density tumor with an ill-defined margin at the arterial phase in the pancreatic head. The tumor involved the common hepatic artery, left hepatic artery bifurcated from the common hepatic artery, and gastroduodenal artery, and was in contact with the portal vein. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed an uptake in the pancreatic head but no evidence of distant metastasis. The tumor was diagnosed as an adenocarcinoma of the pancreatic head and staged unresectable because the common and left hepatic arteries were involved. Hence, the patient underwent seven courses of conversion-intended chemotherapy using gemcitabine and nab-paclitaxel for pancreatic ductal adenocarcinoma over 7 months. After chemotherapy, the tumor shrank to 10 × 10 mm on contrast-enhanced MDCT. Consequently, the boundary between the tumor and major vessels of the common and left hepatic arteries and the portal vein became clear, and the involvement of the arteries with the tumor was evaluated to be released. The contact of the tumor to the portal vein also reduced to less than half the circumference of the portal vein. FDG-PET showed decreased accumulation in the tumor. Hence, the tumor was judged resectable, and pancreaticoduodenectomy was performed. The tumor and major blood vessels were easily dissected and R0 resection was achieved. The patient experienced no major complications and was discharged on postoperative day 28. The tumor was revealed as ASCP via pathological examination. The patient is alive and recurrence-free seven months after surgery. This is the first report of successful R0 resection for an initially unresectable ASCP following conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen. ConclusionsConversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen may be effective for ASCP.

Pancreatic Arteriovenous Malformation Presenting with Upper Gastrointestinal Bleeding: Treatment with Transarterial Embolization—A Case Report

AbstractPancreatic arteriovenous malformations (AVMs) are a rare entity among visceral AVMs and less common cause of gastrointestinal bleeding. We report a case of pancreatic AVM in a 45-year-old man who presented with upper gastrointestinal bleeding and duodenal ulcers, and was hemodynamically unstable. Ultrasound and computed tomography (CT) of the abdomen showed multiple dilated arterial channels in the head region of the pancreas, arising from the gastroduodenal artery, with early filling of the portal vein, suggestive of an AVM. Transarterial embolization was performed by selectively embolizing the arterial feeders using poly-vinyl alcohol (PVA) particles. Postembolization, obliteration of the AVM was seen. On follow-up 2 months later, the patient was clinically stable.

Differences in the course of hepatocellular carcinoma depending on the DAA treatment

Background and aims: 58 million people live with chronic hepatitis C virus (HCV) infection which can lead to liver cirrhosis and hepatocellular carcinoma (HCC). Currently, a non-interferon therapy based on direct-acting antivirals (DAA) is the standard treatment of HCV infection. This study aimed to assess the occurrence of HCC after treatment with DAA and evaluate whether the course of the disease and liver function is different in patients treated with DAA compared to those who did not receive such therapy. Materials and methods: We studied the population of adult patients from the 2015-2021 period and analyzed the demographic and clinical data, including alcohol abuse, liver enzymes, Child-Pugh and model for end-stage liver disease scores, imaging tests, liver biopsy and elastography, if performed. The Mann-Whitney U and the McNemar’s tests were used. The p-value was set at 0.05. Results: The study included n=34 patients with HCC. In this group n=22 patients (61%) were diagnosed with a chronic HCV infection and n=11 (50%) were receiving DAA treatment. Patients who were receiving DAA developed multiple HCC significantly less often compared to patients not treated with DAA (45.5% vs. 69.6%). We also observed a significantly less common occurrence of portal vein thrombosis (8.7% vs. 18.2%) and distant metastases (0.0% vs. 13.0%) in patients with HCC receiving DAA. Patients with HCC who underwent DAA therapy had significantly lower levels of serum liver enzymes in comparison with patients diagnosed with HCC and not receiving DAA. Conclusions: HCC occurring in patients treated with DAA was more often associated with lymphadenopathy, multiple tumors, portal vein thrombosis and distant metastases probably due to restricted treatment qualification criteria. DAA treatment led to a decrease in the inflammatory activity in the liver. It is important to adjust qualification protocols so that all patients suffering from chronic HCV infection could receive the treatment as soon as possible.

Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion.

Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.

Variceal bleeding following treatment with atezolizumab plus bevacizumab in two patients with unresectable hepatocellular carcinoma.

Bleeding-related adverse events may occur due to anti-vascular endothelial growth factors. Here, we report two cases of variceal rupture during atezolizumab plus bevacizumab (ATZ/BV) treatment for unresectable hepatocellular carcinoma (u-HCC).Case 1 involved a man in his 60s with alcoholic liver cirrhosis (LC) and u-HCC. Seventy-four days after ATZ/BV administration, the patient was admitted for hematemesis. Upper esophagogastroduodenoscopy (EGD) revealed worsening of the esophageal varices (EVs) to F2 grade with active bleeding. Endoscopic variceal ligation successfully achieved hemostasis.Case 2 involved a man in his 70s with alcoholic LC and u-HCC. The patient was admitted with hematemesis 114days after ATZ/BV administration. During EGD, the EVs deteriorated to F3 grade, although hemostasis had already been achieved. The evaluation was discontinued during the observation stage because of the worsening hepatic reserve.Neither patient had EVs warranting prophylactic treatment before ATZ/BV administration, showed a partial tumor response, or had portal vein tumor thrombus. Both patients demonstrated increased total diameters of the collateral veins and splenic volume compared to those before treatment. These findings suggest that ATZ/BV treatment may increase portal pressure. In conclusion, the administration of ATZ/BV to patients with LC and u-HCC necessitates careful management of EVs aggravation and rupture.

Lymphangiogenesis in the liver of biliary atresia

BackgroundLymphatic vessels (LVs) play a crucial role in immune reactions by serving as the principal conduits for immune cells. However, to date, no study has analyzed the morphological changes in the LVs of patients with biliary atresia (BA). In this study, we aimed to determine the morphological changes in the LVs irrigating the liver in patients with BA, elucidate their correlations with the morphology of the portal vein (PV) branches, and discuss their etiopathogenetic significance.MethodsMorphometric analyses of liver biopsy specimens from patients treated between 1986 and 2016 were performed. The parameters measured were as follows: the whole liver area of the specimen, fibrotic area, number of LVs, LVs without patent lumen (designated as Ly0) and PV branches, and diameters of the LVs with patent lumen and the PVs.ResultsThe numbers of LVs, Ly0, and PV branches per unit area of the whole liver specimen were significantly higher in patients with BA than in control participants with liver disease and those with normal livers. However, no correlation was observed between the fibrotic area and the average diameter of LVs or PVs, and between the fibrotic area and the number of LVs or PV branches. Furthermore, no correlation was observed between the total number of LVs and the number of PV branches.ConclusionsThe present study showed a significant increase in the number of total LVs and Ly0, characterized by a high Ly0 to total LVs ratio, suggesting that lymphangiogenesis occurs in the liver of patients with BA.

Presence of Modified Peptides with High Bioavailability and Angiotensin-Converting Enzyme Inhibitory Activity in Japanese Fermented Soybean Paste (Miso).

Not only free amino acids and normal short-chain peptides but also modified amino acids, such as N-acetyl- and N-formyl amino acids, monoamines, polyamines, and modified peptides, such as isomerized aspartyl peptides, pyroglutamyl peptides, and diketopiperazines, were identified in Japanese fermented soy paste (miso) prepared using different fungal starters, rice, barley, and soybean-koji. One hour after oral administration of water extract of soybean-koji miso to rats, the modified peptides increased significantly in the lumen upon the ingestion, while the normal peptides did not. In the blood from the portal vein and abdominal vena cava, 17 and 15 diketopiperazines, 16 and 12 isomerized aspartyl peptides, and 2 and 1 pyroglutamyl peptides significantly increased to approximately 10-400 nM, respectively. The modified peptides, which increased in rat blood, showed angiotensin-converting enzyme (ACE) inhibitory activity in a dose-dependent manner, indicating multiple ACE inhibitory peptides with high bioavailability in miso. Among them, l-β-Asp-Pro showed the highest ACE inhibitory activity (IC50 4.8 μM).

Rapid deterioration of steatotic liver disease due to portal vein stenosis after pancreaticoduodenectomy

Steatotic liver disease after pancreatoduodenectomy occurs due to various factors, such as exocrine pancreatic insufficiency, impaired intestinal absorption, and malnutrition. The mechanism of steatogenesis differs to that of conventional steatotic liver disease associated with obesity and insulin resistance. We experienced a rare case of rapidly progressive steatotic liver disease accompanied by portal vein stenosis in the early postoperative period after subtotal stomach-preserving pancreaticoduodenectomy for distal cholangiocarcinoma. Although there was a complication due to postoperative drain infection, the patient was discharged from hospital with no nutritional problems. Two months postoperatively, the patient presented to the emergency room with dyspnea. CT showed a markedly steatotic liver, ascites, and portal vein stenosis. A portal vein stent was inserted transhepatically and the steatotic liver disease gradually improved. During the postoperative course, there were no problems indicated by nutritional markers; although the patient had diarrhea associated with postoperative pancreatic exocrine insufficiency, the symptoms were mild and improved after administration of oral pancrelipase. Before the intervention, the patient had intestinal edema, exacerbation of diarrhea, and a low serum zinc concentration, suggesting that impaired absorption caused by intestinal blood stasis and gut barrier dysfunction contributed to the development of steatotic liver disease.

Adipose tissue-liver cross-talk: a route to hepatic dysfunction in pregnant women with obesity.

Obesity during pregnancy has been escalating, becoming a huge problem that poses consequences not only for the health of the offspring but also for the maternal well-being. Women's adipose and hepatic tissue metabolism undergoes significant changes during the gestational period. During pregnancy, obesity is a primary instigator of steatosis, increasing the risk of non-alcholic fatty liver disease (NAFLD), now recognized under the updated nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). Pregnant women with obesity present higher levels of free fatty acids and glucose, reduction in insulin sensitivity, and adipose tissue endocrine dysregulation. Furthermore, obesity-induced modifications in clock genes and lipid-associated gene expression within adipose tissue disrupt crucial metabolic adaptations, potentially culminating in adipose tissue dysfunction. Thus, the liver experiences increased exposure to free fatty acids through the portal vein. Higher uptake of free fatty acids into the liver disrupts hepatic lipid oxidation while enhances lipogenesis, thereby predisposing to ectopic fat deposition within the liver. This review focuses on the obesity-induced changes during pregnancy in both liver and adipose tissue metabolism, elucidating how the metabolic crosstalk between these two organs can be dysregulated in pregnant women living with obesity.

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.

The potential role of Akkermansia muciniphila in liver health.

Akkermansia muciniphila (A. muciniphila) is a 'star strain' that has attracted much attention in recent years. A. muciniphila can effectively regulate host metabolism, significantly affect host immune function, and play an important role in balancing host health and disease. As one of the organs most closely related to the gut (the two can communicate through the hepatic portal vein and bile duct system), liver is widely affected by intestinal microorganisms. A growing body of evidence suggests that A. muciniphila may alleviate liver-related diseases by improving the intestinal barrier, energy metabolism and regulating inflammation through its protein components and metabolites. This paper systematically reviews the key roles of A. muciniphila and its derivatives in maintaining liver health and improving liver disease.

Portal vein hypoplasia is present in patients with biliary atresia at the time of diagnosis.

In patients with biliary atresia (BA), severe portal hypertension (HTN) develops even with successful bile flow restoration, suggesting an intrinsic factor driving portal HTN independent from bile obstruction. We hypothesize that patients with BA have abnormal portal vein (PV) development, leading to PV hypoplasia. In this observational cohort study, we enrolled patients who were referred to a tertiary center from 2017 to 2021 to rule out BA. Newborns who underwent computed tomography angiogram as a clinical routine before intraoperative cholangiogram, and laparoscopic Kasai hepatoportoenterostomy. The diameter of the PV and hepatic artery (HA) were compared to the degree of liver fibrosis in the wedge biopsies. The jaundice clearance, native liver survival, and clinical portal hypertensive events, including ascites development and intestinal bleeding, were assessed. 47 newborns with cholestasis were included in the cohort; 35 were diagnosed with BA. The patients with BA had a smaller median PV diameter (4.3 vs. 5.1 mm; p < 0.001) and larger median HA diameter (1.4 vs. 1.2 mm; p < 0.05) compared to the patients with other forms of cholestasis. The median PV and HA diameter did not correlate with the degree of liver fibrosis. Among 35 patients with BA, 29 patients (82.9%) achieved jaundice clearance, and 23 patients (65.7%) were alive with their native liver at two years of age. Seven patients (20%) developed intestinal bleeding, and seven patients (20%) developed ascites, with one overlapping patient. PV hypoplasia is present in patients with BA independent of liver fibrosis at the time of diagnosis.

Morphological and Histological Description of Spiny Dogfishshark Liver, Squalusacanthais(Linnaeus,1758),Elasmobranchii,Squaliformes

The current study describes the morphological and histological appearance of the liver of the spiny dogfish Squalusacanthais, which is classified as Class: Chondrichthyes, Subclass: Elasmobranchi. Morphologically, the liver was observed as large, and consists of two symmetrical lobes connected from the upper side, and the gallbladder was observed in the right lobe. Histologically, liver sections were prepared with H&amp;E stain, and examined with a light microscope. Hepatic parenchyma was surrounded by a capsule of connective tissue and primarily composed of hepatocytes. The nuclei of these cells were observed at the terminal site, with lipid droplets in the cytoplasm. Central veins were observed, surrounded by connective tissue and lined with a squamous epithelial layer. Hepatocytes were, separated by numerous blood sinusoids with connective tissue. Blood arteries were observed, surrounded by thick muscular fiber walls and narrow lumens compared to veins. The portal vein was observed, along with the artery and bile duct, surrounded by a thick connective tissue. The bile duct was surrounded by a layer of muscular fibers, lined with a simple columnar epithelial layer with clear nuclei, and a connective tissue layer. Melanin-containing cells were observed, but no hepatic lobules or connective tissue were seen between them. Additionally, Hepato-pancreatic tissue was not identified.