Portal Vein Wall Research Articles

An ultrasound multiparametric method to quantify liver fat using magnetic resonance as standard reference.

There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference. Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis. The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73). Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.

Ultrasound imaging findings in primary biliary cholangitis

BackgroundOur study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC).MethodsWe prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage.ResultsThe typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3).ConclusionsThe ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values.

Fibro-scan Based Score and Novel Noninvasive Serum Marker, FGF-21, to Assess Liver Fibrosis in Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. Aim of the Work This prospective cohort study aims to develop and validate noninvasive scoring system for assessment liver fibrosis in morbidly obese patients with NAFLD. Subjects and Methods This is a Prospective cohort study, was carried out on 50 morbidly obese patients selected from endocrinology department, AIN SHAMS UNIVERSITY, through a period of six months. Results The main results of the study revealed that: There were 32(64.0%) male and 18(36.0%) female with mean age 40.48 (± 12.16) SD. There were 14(28.0%) between (20 -30), 11(22.0%) between (30-40), 9(18.0%) between (40-50) and 16(32.0%) ≥50. Mean Weight (Kg) was 106.6 (± 13.31) SD with range (82.50 – 145.5), mean Height (Cm) was 171.7 (± 6.25) SD with range (158.0 – 185.0), mean BMI (Kg/m2) was 36.17 (± 4.15) SD with range (29.30 – 43.40), mean Waist circumference 113.1 (± 8.64) SD with range (92.0 – 129.0). There were 37(74.0%) with Comorbidity. 10(20.0%) have DM, 11(22.0%) have HTN, 11(22.0%) have CDK and 5(10.0%) have COPD. mean Hb was 12.24 with range (11.0 – 13.50), mean Plts was 193.2 with range (151.0 – 250.0), mean WBCs with range (4.70 – 8.20), mean AST was 85.20 with range (21.0 – 210.0), mean ALT was 86.64 with range (15.0 – 212.0), mean Cholesterol was 181.4 with range (122.0 – 248.0), mean Triglycerides was 156.3 with range (12.0 – 294.0), mean LDL was 119.1 with range (61.0 – 193.0), mean HDL was 61.32 with range (23.0 – 96.0), mean GGT (U/l) was 18.22 with range (7.0 – 33.0), mean HBA1C was 5.72 with range (4.70 – 9.30), mean Fasting blood sugar was 101.8 with range (81.0 – 155.0) and mean Uric acid was 6.23 with range (4.0 – 10.10). Regarding ultrasound outcome there were 33(66.0%) have Gallbladder wall blurring, 34(68.0%) have Portal vein wall blurring, 42(84.0%) have Hepatic vein blurring and 50 (100.0%) have fatty liver. Regarding fibrosis grade there were 12(24.0%) F1, 17(34.0%) F2, 18(36.0%) F3 and 3(6.0%) F4. Conclusion That the combination of Fibroscan and, APRI, FGF-21 and FIB-4 methods provides a valuable approach for assessing liver fibrosis in NAFLD patients. This can eliminate the need for liver biopsy in patients without clear indication. In addition, several recent studies have also validated the used of non-invasive markers in the diagnosis of NAFLD. The establishment of a national program for the recognition of NAFLD is therefore essential to reduce the risk of liver disease progression.

Evaluation of lead exposition length on the liver and intestinal histoarchitecture of eared dove (Zenaida auriculata).

Lead (Pb) is a metal that can produces irreversible damage in living organisms. Some studies had reported that Pb produces histophysiological alterations in the digestive system (mainly liver) of birds; however, the effect of this metal on small intestine has not been fully examined. Additionally, little information is available on Pb disturbances in native birds of South America. The present study aimed to evaluate the effect of different Pb exposure times on blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity and on the histological and morphometric characteristics of the digestive system (liver and proximal intestine) of eared doves (Zenaida auriculata). A decrease of the blood δ-ALAD activity, dilatation of blood vessels and leukocyte infiltrates in intestinal submucosa and muscular layers, and reduction of the enterocyte nuclear diameter and Lieberkühn crypts area were observed. In liver were noted steatosis, proliferation of bile ducts, dilated sinusoids, leukocyte infiltrates, and melanomacrophage centers. The portal tract area and the thickness of the portal vein wall were increased. In conclusion, the results showed that Pb produces histological and morphometric alterations on the liver and small intestine according to the exposure time, which should be considered when the dangerousness of environmental pollutants is evaluated in wild animals.

Histological features of the structure of the portal vein of the liver and splenic vein in portal hypertension

BACKGROUND: Studies on the morphological and hemodynamic changes in the structure of the portal vein of the liver and the splenic vein in various pathologies, one of which is portal hypertension, remains relevant.&#x0D; AIM: To perform a histological study on the structure and thickness of the membranes of the portal vein of the liver and splenic vein in people of different age groups with normal conditions and with portal hypertension.&#x0D; MATERIALS AND METHODS: Sectional material for the study of the portal vein of the liver and splenic vein was obtained from 89 people aged 730 years old who died from injuries incompatible with life. A total of 57 cases had a history of portal hypertension during life, and the remaining 32 cases were considered as controls. The cellular and tissue components of the vein walls were studied in paraffin sections stained with hematoxylineosin and Van Giesons stain (picric acid and fuchsin) using Weigerts hematoxylin.&#x0D; RESULTS: The thicknesses of the inner and middle membranes of venous vessels significantly increased in all age groups with portal hypertension relative to those in the control. The pathological features of changes in the thickness and microstructure of the components of the portal vein wall of the liver and splenic vein in topographically different parts of the veins were observed.&#x0D; CONCLUSION: The histological and morphometric examination of the wall of the portal vein of the liver and the splenic vein in normal cases and cases of portal hypertension syndrome in different age periods revealed not only the structural features of the portal vein of the liver and splenic vein, but also the features of age-related pathomorphological changes in the individual parts of the veins and in each of the membranes. Such features are of considerable interest for clinical medicine.

ИССЛЕДОВАНИЕ СОКРАТИТЕЛЬНОЙ АКТИВНОСТИ ПОРТАЛЬНОЙ ВЕНЫ МЫШИ В ПОЛЕТНОМ ЭКСПЕРИМЕНТЕ «БИОН-М2»: ОБОСНОВАНИЕ АКТУАЛЬНОСТИ И РАЗРАБОТКА ЭКСПЕРИМЕНТАЛЬНОЙ МОДЕЛИ

Redistribution of blood in the vascular system in the condition of gravitational unloading causes changes in venous blood flow inboth humans and laboratory animals; however, dependence of these changes on the alterationsin contractile activity of venous walls and mechanisms involved are not sufficientlyexplored. Purpose of the work is to design an experimental setupand procedure for studying the effects of microgravity on the venous vesselsin mouse, the most common object of animalspace experiments. The proposed procedure consists of recording the contractile activity of the longitudinal smooth layer of the portal vein wall, and itschanges due to actionof pharmacological agents. Frequency of venous contraction changes in response to different factors more significantly than the contraction amplitude and tone level. The resultswill serve as a basis for developing an optimal protocol of studying the mechanisms of changes in venous contractility in mice as part of space experiment BION-M2.

Age-related changes of rats portal vein hemodynamics and morphometry

Introduction. Age-related changes of blood flow parameters and hepatic portal vein wall morphometry are one of the topical and insufficiently investigated issues of liver hemodynamics. The aim was to study changes of portal hemodynamics and to analyze the portal vein wall morphometry of rats at different age periods. Materials and methods. 60 mongrel rats of both sexes weighing 120–350 g were divided into three age groups. The first group included 20 rats aged 1 month, the second – 20 rats aged 6–12 months and the third – 20 rats aged more than 18–24 months. The qualitative and quantitative portal vein hemodynamics parameters were obtained by ultrasound scanners under zoletil-xylazine anesthesia. Morphometric examination of the portal vein was performed. Digital data were processed by methods of variational statistics. Results. The diameter of the portal vein in groups II and III was greater than the corresponding parameter in group I (R = – 0.40 and R = 0.64, respectively). The time-averaged average blood flow rate in the II age group increased by 9.11 % compared to the I group, decreased by 10.43 % in the III group (the differences are statistically unreliable). The volumetric blood flow rate increased moderately in age groups II and III compared to group I (by 13.07 and 11.13 %, respectively; the difference is statistically unreliable). The ratio of the volumetric blood flow rate to the weight of the animal in the II age group increased by 3.85 % compared to the I group, decreased by 11.54 % in the III group (the differences are statistically unreliable). Since the mass of animals significantly increased with age, the portal vein volumetric blood flow of old animals is likely to be decreased. Mature and old rats demonstrated significant decrease of the muscle membrane thickness, the Kernogan index and the width of the collagen layer. Conclusion. Age-related changes of rats portal hemodynamics resulted in a slight reliable increase of portal vein diameter and its cross-sectional area. Linear and volumetric parameters of blood flow were found not to have statistically reliable dependence on the age and weight of animals. Morphometric parameters of the rats portal vein wall were revealed to have pronounced changes in different age groups. The aging of the portal vein wall of elder rats consisted in a significant decrease of the muscle membrane thickness, the Kernogan index and the width of the collagen layer.

A New SteatoScore in the Evaluation of Non-Alcoholic Liver Disease in Oncologic Patients.

PurposeThe aims of this study were to evaluate the reproducibility of a new multi-parametric steatoscore (new SteatoScore) in oncologic patients with non-alcoholic fatty liver disease (NAFLD) and to compare it with computed tomography (CT).Materials and MethodsFifty-one (31 men, 20 women) oncologic patients, with a mean age and weight of 63.9 years and 78.33 kg, respectively, were retrospectively enrolled in the study. Patients underwent ultrasound (US) and computed tomography (CT) examinations as part of their oncologic follow-up protocol. US examinations were performed by using a 3.5-MHz convex probe. During the US examination, three standardized clips were obtained in each patient. Two operators performed all measurements, one of whom repeated the processing twice in 1 year. Hepatic/renal ratio (HR), attenuation rate (AR), diaphragm visualization (DV), hepatic/portal vein ratio (HPV), and portal vein wall visualization (PVW) were acquired and calculated by using Matlab and inserted in a multi-parametric algorithm called new SteatoScore. On unenhanced CT scan, hepatic attenuation (HA), liver-spleen difference (L-S), and liver/spleen ratio (L/S) were measured by placement of a region of interest (ROI) within liver and spleen parenchyma, avoiding areas with vessels and biliary ducts.ResultsThe intra-observer variability was greater than the inter-observer one, with intraclass correlation coefficient (ICC) values of 0.94 and 0.97, respectively. Correlation between single US and CT parameters provided an agreement in no case exceeding 50%. New SteatoScore showed high reproducibility, and high coefficient of correlation with L-S (R = −0.64; p < 0.0001) and L/S (R = −0.62; p < 0.0001) at CT.ConclusionNew SteatoScore has a high reproducibility and shows a good correlation with unenhanced CT in evaluation of oncologic patients with NAFLD.

Correlation between Liver Ultrasonography with AST and ALT Value in Suspect Hepatitis

BACKGROUND: Liver ultrasonography is frequently recommended in Hepatitis patients. Hepatitis is liver inflammation caused by infection with microorganisms, drugs, and alcohol. Hepatitis causes liver cell damage and sometimes can change the echostructure of ultrasonography. These changes have affected the value of Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT).&#x0D; AIM: The study aimed was to identify the correlation of liver ultrasonography with liver function (AST / ALT) in patients with suspected Hepatitis.&#x0D; METHOD OLOGY: The method was a Cross-Sectional approach to identify the relationship of liver ultrasonography, including echostructure, size, edge or surface, portal vein, gall bladder with AST and ALT in patients with suspected Hepatitis. The subjects were from PKU Muhammadiyah Hospital Yogyakarta, 2015-2018, 18-60 years old. They were identified using ALT and AST and proposed ultrasonography of the liver and gallbladder. The samples size consisted of 68 men and 32 women. Liver enzyme and ultrasonography did not know the results of this examination (blind). The relationship between the two variables was analyzed through the Chi-Square.&#x0D; RESULTS: The result was showed a significant relationship between liver ultrasonography, including the echostructure, size, portal vein dilatation with AST and ALT, and p-value for echo structure to AST 0.05 and ALT 0.02. The p-value of liver size revealed an AST of 0.03 and a p-value of a portal venous wall with AST 0.06 and with ALT of 0.02.&#x0D; CONCLUSIONS: There was a significant relationship between echostructure, liver size, and portal vein wall with AST and ALT. The liver surface edge and gallbladder had no significant relationship with AST and ALT.

Portal vein wedge resection and patch venoplasty using autologous and homologous vein grafts during surgery for hepatobiliary malignancies.

Obtaining tumor-free resection margins is one of the most important factors for achieving favorable prognosis of patients undergoing resection for hepatobiliary malignancies. In this study, we present our experience of portal vein (PV) wedge resection and patch venoplasty using autologous or homologous vessel grafts for resecting perihilar cholangiocarcinoma, hepatocellular carcinoma, and distal bile duct cancer. Case 1 was 68-year-old male patient with type IV perihilar cholangiocarcinoma who underwent central bisectionectomy with caudate lobectomy and bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 14 months after surgery. Case 2 was 77-year-old male patient with type IIIA perihilar cholangiocarcinoma who underwent left medial sectionectomy with caudate lobectomy, bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 17 months after surgery. Case 3 was 54-year-old male patient with hepatitis B virus-associated liver cirrhosis and hepatocellular carcinoma with PV tumor thrombus who underwent left hepatectomy. The PV wall defect was repaired with an autologous greater saphenous vein patch. This patient survived 11 months after surgery. Case 4 was 65-year-old female patient with distal bile duct cancer who underwent pylorus-preserving pancreaticoduodenectomy, and main PV wedge resection and patch venoplasty with a cryopreserved iliac artery allograft patch. This patient survived 21 months after surgery. In conclusion, PV wedge resection and patch venoplasty can be used to facilitate complete tumor resection in patients undergoing various extents of surgical resection for hepatobiliary malignancies.

Standard radical bile duct surgery focused on vascular reconstruction

Since the mid bile duct cancers often involve the intrapancreatic bile duct, resection of the extrahepatic bile duct results in a tumor-positive distal resection margin. Extended extrahepatic bile duct resection is a surgical procedure to obtain a tumor-free distal resection margin during extrahepatic bile duct resection, in which R0 resection can be achieved without performing pancreatoduodenectomy. The extent of intrapancreatic bile duct excavation was designed to resemble making a several cm-long funnel. The surgical procedure for pancreatic excavation was derived from those used for choledochal cyst excision. Special attention should be paid to prevent pancreatic leak at the bile duct excavation portion at the pancreatic head. If the proximal extrahepatic bile duct is tumor-positive, major or parenchyma-preserving hepatectomy is necessary to achieve R0 resection. Resection of segment I and segment IV with bile duct resection offers very wide operative field and allows wider extent of hilar bile duct resection, thus presents the most common type of parenchyma-preserving hepatectomy. When the portal vein is focally involved by the tumor, hilar portal vein wedge resection and roofing patch venoplasty using a autograft or homograft vein patch is a useful option to facilitate complete tumor resection in patients undergoing bile duct resection. Regarding roofing patch venoplasty, it is important to make the portal vein wall defect as small as possible as well as to make the size of the vein patch either twice or three times larger than the defect size at the portal vein wall. The patch should be large enough to make the patch roof redundant. Even if the patch roof appears to be noticeably redundant at the time of operation, it is vulnerable to shrinkage due to compression of the jejunal loop and through degenerative changes of the patch per se. The availability of vein autografts or homografts facilitates combined vascular resection and reconstruction during aggressive surgery for hepatobiliary malignancies.

Portal vein wedge resection and patch venoplasty using autologous and homologous vein grafts during surgery for hepatobiliary malignancies

Obtainment of tumor-free resection margins is one of the most important factors for favorable prognosis of patients undergoing resection for hepatobiliary malignancies. In this study, we present our experience of portal vein (PV) wedge resection and patch venoplasty using autologous or homologous vessel grafts used in resection for perihilar cholangiocarcinoma, hepatocellular carcinoma and distal bile duct cancer. Case 1: A 68-year-old male patient with type IV perihilar cholangiocarcinoma underwent central bisectionectomy with caudate lobectomy and bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 14 months after surgery. Case 2: A 77-year-old male patient with type IIIA perihilar cholangiocarcinoma underwent left medial sectionectomy with caudate lobectomy and bile duct resection, and PV wedge resection and patch venoplasty with a cryopreserved iliac vein allograft patch. This patient survived 16 months after surgery. Case 3: A 54-year-old male patient with hepatitis B virus-associated liver cirrhosis and hepatocellular carcinoma with PV tumor thrombus underwent left hepatectomy. The PV wall defect was repaired with an autologous greater saphenous vein patch. This patient survived 11 months after surgery. Case 4: A 65-year-old female patient with distal bile duct cancer underwent pylorus-preserving pancreaticoduodenectomy and main PV wedge resection and patch venoplasty with a cryopreserved iliac artery allograft patch. This patient survived 21 months after surgery. In conclusion, PV wedge resection and patch venoplasty provide a useful option to facilitate complete tumor resection in patients undergoing various extents of surgical resection for hepatobiliary malignancies.

Phenotypic Characterization of CD4+ T Lymphocytes in Periportal Fibrosis Secondary to Schistosomiasis.

Schistosomiasis is a parasitic disease that affects about 166 million people around the world. It is estimated that 5%–10% of individuals with schistosomiasis develop severe forms of the disease, which are characterized by pulmonary hypertension, ascites, periportal fibrosis, and other significant complications. The chronic phase of the disease is associated with a Th2 type immune response, but evidence also suggests there are roles for Th1 and Th17 in the development of severe disease. The aim of this study was to evaluate the CD4+ T lymphocyte profile of patients with different degrees of periportal fibrosis secondary to schistosomiasis. These individuals had been treated for schistosomiasis, but since they live in a S. mansoni endemic area, they are at risk of reinfection. They were evaluated in relation to the degree of periportal fibrosis and classified into three groups: without fibrosis or with incipient fibrosis (WF/IFNE), n=12, possible periportal fibrosis/periportal fibrosis, n=13, and advanced periportal fibrosis/advanced periportal fibrosis with portal hypertension, n=4. We observed in the group without fibrosis a balance between the low expression of Th2 cytokines and high expression of T reg cells. As has already been described in the literature, we found an increase of the Th2 cytokines IL-4, IL-5, and IL-13 in the group with periportal fibrosis. In addition, this group showed higher expression of IL-17 and IL-10 but lower IL-10/IL-13 ratio than patients in the WF/IFNE group. Cells from individuals who present any level of fibrosis expressed more TGF-β compared to the WF/IFNE group and a positive correlation with left lobe enlargement and portal vein wall thickness. There was a negative correlation between IL-17 and the thickness of the portal vein wall, but more studies are necessary in order to explore the possible protective role of this cytokine. Despite the fibrosis group having presented a higher expression of pro-fibrotic molecules compared to WF/IFNE patients, it seems there is a regulation through IL-10 and T reg cells that is able to maintain the low morbidity of this group.

Ultrasonographic measurement of the vascular wall thickness and intima-media thickness in patients with Behçet’s disease with symptoms or signs of vascular involvement: A cross-sectional study

Objectives This study aims to measure and compare bilateral carotid intima-media thickness (CIMT), bilateral jugular, common femoral, and main portal vein wall thicknesses (VWTs) in Behçet’s disease (BD) patients with and without vascular involvement to obtain a cut-off value for vascular complications and determine their relationship with disease activity.Patients and methods Sixty-three BD patients (41 males, 22 females; median age: 38.0 years; min 20 - max 71 years) and 30 healthy control subjects (14 males, 16 females; median age: 40.3 years; min 21 - max 60 years) were included in this cross-sectional study between February and March 2020. According to imaging findings, BD patients were divided into two groups as those with and without vascular complications. Disease duration, medical treatment and BD manifestations of patients were questioned. Disease activity was evaluated using the Behçet's Disease Current Activity Form (BDCAF) and the Behçet's Syndrome Activity Scale (BSAS). Two radiologists blinded to the diagnosis of BD used ultrasound to measure VWT and CIMT. Receiver operating characteristics were assessed to obtain sensitivity and specificity values for each VWT and CIMT.Results The groups were similar in terms of age, sex, and body mass index (p>0.05). There was a significant difference between the BD groups when the BDCAF and BSAS scores were compared, while there was no difference between them in terms of disease duration and medical treatment (p>0.05). All VWTs and CIMTs were significantly higher in patients with BD compared to healthy controls (p<0.05). There was no significant difference between the BD groups in terms of CIMT, jugular and common femoral VWTs (p>0.05). But portal VWT was significantly higher in patients with vascular involvement (p<0.05). A cut-off value of ≥1.35 mm yielded a sensitivity of 79.2% and a specificity of 82.4% for the diagnosis of vascular involvement with the highest Youden's index (area under the curve, 0.869; 95% confidence interval, 0.783 to 0.956).ConclusionPortal VWT has high sensitivity and specificity for the screening of vascular involvement in patients with BD.

The Efficacy of the Hepatocyte Spheroids for Hepatocyte Transplantation

The safety and short-term efficacy of hepatocyte transplantation (HCTx) have been widely proven. However, issues such as reduced viability and/or function of hepatocytes, insufficient engraftment, and lack of a long-term effect have to be overcome for widespread application of HCTx. In this study, we evaluated hepatocyte spheroids (HSs), formed by self-aggregation of hepatocytes, as an alternative to hepatocytes in single-cell suspension. Hepatocytes were isolated from C57BL/6 J mice liver using a three-step collagenase perfusion technique and HSs were formed by the hanging drop method. After the spheroids formation, the HSs showed significantly higher mRNA expression of albumin, ornithine transcarbamylase, glucose-6-phosphate, alpha-1-antitrypsin, low density lipoprotein receptor, coagulation factors, and apolipoprotein E (ApoE) than 2 dimensional (2D)-cultured hepatocytes (p < 0.05). Albumin production by HSs was significantly higher than that by 2D-cultured hepatocytes (9.5 ± 2.5 vs 3.5 ± 1.8 μg/dL, p < 0.05). The HSs, but not single hepatocytes, maintained viability and albumin mRNA expression in suspension (92.0 ± 2.8% and 1.03 ± 0.09 at 6 h). HSs (3.6 × 106 cells) or isolated hepatocytes (fSH, 3.6 × 106 cells) were transplanted into the liver of ApoE knockout (KO-/-) mice via the portal vein. Following transplantation, serum ApoE concentration (ng/mL) of HS-transplanted mice (1w: 63.1 ± 56.7, 4w: 17.0 ± 10.9) was higher than that of fSH-transplanted mice (1 w: 33.4 ± 13.0, 4w: 13.7 ± 9.6). In both groups, the mRNA levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, MCP-1, and MIP-1β) were upregulated in the liver following transplantation; however, no significant differences were observed. Pathologically, transplanted HSs were observed as flat cell clusters in contact with the portal vein wall on day 7. Additionally, ApoE positive cells were observed in the liver parenchyma distant from the portal vein on day 28. Our results indicate that HS is a promising alternative to single hepatocytes and can be applied for HCTx.

Immunohistological analysis on distribution of smooth muscle tissues in livers of various vertebrates with attention to different liver architectures

BackgroundThe liver architecture of vertebrates can be classified into two types, the portal triad type (having periportal bile ducts) and the non-portal triad type (having non-periportal bile ducts). The former is detectable from the hagfish, which is the most ancestral vertebrate, to tetrapod livers whereas many actinopterygian livers have the latter. The aim of the present study is to reveal the distribution of smooth muscle tissue in livers of various vertebrates with attention to their architectures. MethodsSmooth muscle was immunohistochemically compared in hepatic blood vessels and bile ducts of various vertebrates, using an anti-alpha-smooth muscle actin (ASMA) antibody. ResultsSmooth muscle was noted in the gallbladder and hepatic artery in all vertebrates, including the hagfish. Bile ducts having ASMA-positive smooth muscles were absent in the hagfish, but detected in the Chondrichthyes and conserved in actinopterygians with or without portal triads during the evolution of vertebrates. In tetrapods having portal triads, reptiles had a tendency to have strongly ASMA-positive biliary smooth muscle tissues whereas other tetrapods had bile ducts with poor smooth muscle tissues. Although the hagfish livers never had ASMA-positive smooth muscle tissue in the walls of portal and central veins, it was observed in discontinuous distributions or not observed in portal veins and central veins of chondrichthyans and actinopterygians. By contrast, in most tetrapods, ASMA-positive smooth muscle tissue was detectable in portal veins, which supported the adjacent endothelial cells as a circular layer. Central veins did not consistently have smooth muscle tissue in these groups. Discussion and conclusionThe hagfish liver may retain more ancestral characteristics than other vertebrates in terms of smooth muscle distribution in the vascular and biliary systems. Actinopterygians might have a different mechanism of bile transport from tetrapods from their smooth muscle distribution in intrahepatic bile ducts. The circular smooth muscle distribution in portal veins might be a characteristic acquired by tetrapods.

An ultrasound-based referential of body height-adjusted normal liver organometry in school children from Bokito in rural Cameroon

The grading system for ultrasonographic assessment of Schistosoma mansoni morbidity is crucial for evaluation of control programs. This requires prior definition of normal liver organometric ranges in the population from the endemic area. A cross-sectional study was conducted in a S. mansoni endemic area in rural Cameroon. 1002 Participants were screened and 234 of them, free from all common liver-affecting diseases in the area (schistosomiasis, malaria, hepatitis B and C) and with no ultrasonographic signs of liver disease were selected and their liver parameters measured by ultrasonography. All statistics were considered significant for p-values < 0.05. Normal dimensions of livers lobe sizes, portal vein wall thickness and portal vein diameters are reported. The liver organometric data are presented for the entire study population as a whole and separately for males and females as prediction plots, with observed values and fitted regression line with 95% confidence. Reference ranges for liver parameters (size, portal vein thickness and diameter) adjusted for body height established in the current study are novel for Cameroon. The prediction plots generated should improve the accuracy of the assessment of liver morbidity by ultrasonography in the region.

Imaging and Pathological Features of Idiopathic Portal Hypertension and Differential Diagnosis from Liver Cirrhosis

Idiopathic portal hypertension (IPH) mimics liver cirrhosis in many aspects, and no efficient imaging method to differentiate the two diseases has been reported to date. In this study, the imaging and pathological characteristics were analysed for both IPH and cirrhosis. From January 2015 to March 2019, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) images and pathological results from 16 IPH and 16 liver cirrhosis patients, as well as imaging results of 16 normal patients as a control group, were retrospectively reviewed. The age of the patients was 39 ± 20 years. There was a significant difference in the mean lumen diameter, wall thickness and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the main and sagittal portal veins (P < 0.05), as well as in the lumen diameter and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the Segment 3 (S3) portal vein (P < 0.05). In IPH patients, the main imaging changes were portal vein wall thickening, stenosis or occlusion, a low enhancement area along the portal vein in the delay phase in contrast-enhanced imaging, and a non-homogeneous change in T1WI. The corresponding pathological changes included interlobular vein thickening, stenosis, occlusion, portal area fibrosis, and atrophy or apoptosis of hepatocytes. The main imaging characteristic of liver cirrhosis was a nodular change in T1WI, and the related pathological change was pseudolobule formation. The imaging characteristics of IPH include thickening of the portal vein vascular wall, stenosis of the portal vein lumen and the absence of diffuse cirrhosis-like nodules. These imaging features have a definite pathological basis and could help make differential diagnoses between IPH and cirrhosis.

Surgical management of a rare portal vein sarcoma

Presenter: Victor Sandoval MD | Oregon Health and Science University Background: A previously healthy 59-year-old female presented to clinic with intermittent, increasing abdominal pain for several months. Imaging revealed a pathologically enlarged, necrotic lymph node versus neoplasm in the portacaval space (Figure1a). Initial endoscopic ultrasound with biopsy revealed atypical cells. Staging work up revealed no metastatic disease. Following multi-disciplinary liver tumor board review, a repeat biopsy yielded a desmin positive spindle cell neoplasm consistent with leiomyosarcoma. Liver function tests and tumor markers were normal. Body surface area adjusted remnant liver volume following right hepatectomy was estimated to be 32.4%. The common bile duct and right hepatic artery were adherent to tumor. The proximal main and left PV branches were transected, and reconstruction between the main and left PV was performed with 10 mm X 10 mm CryoVein® interposition graft (Figure 1c). Clamp time was 18 minutes and arterial perfusion to the left liver was never compromised. A right hemihepatectomy was performed with a roux limb hepatico-jejunostomy to the left hepatic duct. Postoperatively, the patient had an unremarkable recovery. Duplex ultrasound on post-operative days 1 and 4 showed normal portal and arterial flow. She was discharged on postoperative day 6. Patient remains no evidence of disease 18 months after her surgery. Pathological examination revealed an intermediate grade leiomyosarcoma (Figures 1d). Grossly, the tumor invaded the wall of the right portal vein. Histology showed areas of infiltration into the vein wall. Immuno-stains demonstrated the tumor to be strongly caldesmon positive and smooth muscle actin positive. It was negative for CD117 and DOG1 supporting the diagnosis. Vascular leiomyosarcomas are smooth muscle cell tumors that can present in any vascular structure; venous origin is most common. Mesenteric and particularly extrahepatic portal vein leiomyosarcomas are exceedingly rare. In published reports, patients had normal tumor markers and none demonstrated tumor thrombus. Local recurrence is common. Of the several case reports that include longitudinal follow up, all report local recurrence. Disease-free interval in these reports from date of primary surgery to discovery of unresectable recurrent disease was 12 months, 36 months, and 4 years. Due to the lack of information on vascular leiomyosarcomas, particularly the even rarer subset of extrahepatic portal leiomyosarcomas, there are no established treatment recommendations. Surgical management with a goal of an R0 resection remains the recommended treatment. Neither adjuvant nor pre-operative chemotherapy is routinely indicated. In the IVC leiomyosarcoma population, predictors of lower survival rates include: older age, larger tumors, resection of adjacent organs, and R2 resection. Radiation is often recommended in patients with R1 resections. Careful follow up should include frequent evaluation of graft patency by ultrasound and cross-sectional imaging to identify recurrent disease.

Natural Poisoning by Tephrosia cinerea in Sheep from Western Region of Rio Grande do Norte State, Northeastern Brazil

Background: Tephrosia cinerea is a toxic plant responsible for liver fibrosis, which results in ascites and weight loss in sheep and probably goats. Although T. cinerea is widespread in Brazil, reports of poisoning are described in a few regions, named Eastern “Seridó” region of Rio Grande do Norte state, Central “Sertão” region of Ceará state, and “Sertão” of Paraíba state. Thus, this paper aimed to report the clinical-epidemiological, laboratorial, pathological and ultrasonographic findings of sheep spontaneously poisoned by T. cinerea in the Western region of Rio Grande do Norte state, Northeastern Brazil.Cases: The evaluated cases occurred in sheep raised on properties located in the municipalities of Areia Branca and Tibau, Western region of Rio Grande do Norte state, Northeastern Brazil. In all visited farms, the pasture had a marked predominance of the T. cinerea. Clinical signs included progressive weight loss, dehydration, bilateral abdominal distension, and respiratory dyspnea probably due to diaphragmatic compression. Other less frequent clinical signs were hyporexia, pale mucosae, rough hair coat and polyuria. Hematology revealed leukocytosis by neutrophilia, while serum biochemical analysis revealed increased activities of GGT (mean 96.3 U/L, reference: 20-52 U/L) and ALT (mean 55.0 U/L, reference: 22-38 U/L) and reduced levels of total proteins (mean 5.3 g/dL, reference 6.0-7.9 g/dL), albumin (mean 2.0 g/dL, reference 2.4-3.0 g/dL), and globulins (mean 3.2 g/dL, reference 3.5-7.0 g/dL). Abdominal ultrasonography was performed in one sheep, revealing a large amount of anechoic peritoneal effusion without floating echogenic debris or spots, and distention of hepatic vessels and portal veins. On the other hand, the ultrasonographic examination did not reveal changes in gallbladder, in right kidney and in the size of the liver. Gross pathological findings included severe ascites, moderate hydrothorax and hydropericardium, and liver showing irregular nodular surface, whitish areas and hardened consistency. The ascetic fluid was clear and is volume ranged from 8 to 13.5 liters. Microscopic evaluation of liver revealed hepatocyte necrosis, diffuse deposition of collagen fibers, and ductular proliferation.Discussion: Definitive diagnosis of poisoning by T. cinerea was made by the association of epidemiological, clinical, laboratory and pathological findings. It is known that the plant is part of the botanical composition of the diet of sheep all year long, but the poisoning becomes important mainly during the dry season. Affected sheep showed a typical ascitic condition due to diffuse liver fibrosis. Main ultrasonographic findings corresponded to hyperechoic diffuse diseases patterns, such as lipidoses and toxic liver diseases. The alterations observed in the biochemical panel are consistent with hepatic damage caused by the plant. The hematological findings are suggestive of immune system interference of poisoned sheep, but it is not possible to infer if it were the direct action of some component(s) of the plant or if it would be secondary to the severe nutritional deficiency induced by the poisoning. The toxic principle of T. cinerea remains undetermined, but it is already known that it is not pyrrolizidine alkaloids. The probable pathophysiological mechanism of ascites is the increased blood pressure on the portal vein walls due to the greater resistance of the liver parenchyma, but there should also be some contribution of hypoalbuminemia, which reduces plasmatic colloid osmotic pressure.