Detection of biliary and vascular anatomy in living liver donors: value of gadobenate dimeglumine enhanced MR and MDCT angiography.

PubMed

Artioli, Diana; Tagliabue, Marianna; Aseni, Paolo; Sironi, Sandro; Vanzulli, Angelo

2010-11-01

To evaluate the performance of magnetic resonance (MR) and multidetector computed tomography (MDCT) in the assessment of living donor's vascular and biliary anatomy, having surgical findings as reference standard. Thirty-two living liver donors underwent MR cholangiography (1.5-T; standard cholangiography pulse sequences and delayed acquisitions after administration of biliary contrast agent) for biliary anatomy evaluation. MDCT (16-row multidetector scanner, multiphase protocol, 3mm slice thickness) was also performed in all cases for the assessment of vascular anatomy before transplantation. Hepatic veins (<4mm in diameter) were not considered. MR and MDCT images interpretation was performed by two reviewers by consensus, based on source axial images, multiplanar reformats, and three-dimensional (3D) postprocessing images. Surgical intraoperative findings were used as standard of reference. At surgery, 17 biliary anomalies, 3 portal anomalies, 32 venous and 8 arterial variants were found in the 32 patients. MR correctly identified 15/17 biliary anomalies, with a sensitivity of 88% and a specificity of 93%. MDCT correctly identified 8/8 arterial, 3/3 portal and 29/32 venous variants, with a sensitivity of 100% and 91%, respectively, and a specificity of 100%. MR and MDCT proved to be efficient in evaluating living liver donor's biliary and vascular anatomy. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Human liver proteome project: plan, progress, and perspectives.

PubMed

He, Fuchu

2005-12-01

The Human Liver Proteome Project is the first initiative of the human proteome project for human organs/tissues and aims at writing a modern Prometheus myth. Its global scientific objectives are to reveal the "solar system" of the human liver proteome, expression profiles, modification profiles, a protein linkage (protein-protein interaction) map, and a proteome localization map, and to define an ORFeome, physiome, and pathome. Since it was first proposed in April 2002, the Human Liver Proteome Project has attracted more than 100 laboratories from all over the world. In the ensuing 3 years, we set up a management infrastructure, identified reference laboratories, confirmed standard operating procedures, initiated international research collaborations, and finally achieved the first set of expression profile data.

Quantification of HCV RNA in Liver Tissue by bDNA Assay.

PubMed

Dailey, P J; Collins, M L; Urdea, M S; Wilber, J C

1999-01-01

With this statement, Sherlock and Dooley have described two of the three major challenges involved in quantitatively measuring any analyte in tissue samples: the distribution of the analyte in the tissue; and the standard of reference, or denominator, with which to make comparisons between tissue samples. The third challenge for quantitative measurement of an analyte in tissue is to ensure reproducible and quantitative recovery of the analyte on extraction from tissue samples. This chapter describes a method that can be used to measure HCV RNA quantitatively in liver biopsy and tissue samples using the bDNA assay. All three of these challenges-distribution, denominator, and recovery-apply to the measurement of HCV RNA in liver biopsies.

Congenital intrahepatic portohepatic shunt managed by interventional radiologic occlusion: a case report and literature review.

PubMed

Grimaldi, Chiara; Monti, Lidia; Falappa, Piergiorgio; d'Ambrosio, Giuseppe; Manca, Antonio; de Ville de Goyet, Jean

2012-02-01

Congenital intrahepatic portosystemic shunts are rare hepatic vascular anomalies that often lead to severe secondary conditions. A 6-year-old boy was referred for assessment of severe hypoxia, and a large liver mass was diagnosed with such a malformation and was managed by direct closure of the venous fistula by interventional radiology. Follow-up assessment shows normalization of the respiratory condition and a progressive reduction of the vascular liver lesion. Review of literature suggests that radiologic interventions are currently the criterion standard for managing these conditions, with surgery reserved for patients who are not eligible for radiologic procedure and those requiring liver transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Summary of the British Transplantation Society UK Guidelines for Living Donor Liver Transplantation.

PubMed

Manas, Derek; Burnapp, Lisa; Andrews, Peter Antony

2016-06-01

The British Transplantation Society Guidelines for Living Donor Liver Transplantation was published in July 2015 and is the first national guideline in the field of living donor liver transplantation. The guideline aims to review the evidence relating to the evaluation process of both recipient and donor candidates; address the moral and ethical issues surrounding the procedure; outline the technical aspects of the procedure, including the middle hepatic vein controversy and the "small for size syndrome"; review donor and recipient outcomes and complications including donor mortality; and examine evidence relating to the advantages and disadvantages of living donor liver transplantation. In line with previous guidelines published by the BTS, the guideline has used the Grading of Recommendations Assessment, Development and Evaluation system to rate the strength of evidence and recommendations. This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for the delivery of living liver donation in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at http://www.bts.org.uk/BTS/Guidelines_Standards/Current/BTS/Guidelines_Standards/Current_Guidelines.aspx?hkey=e285ca32-5920-4613-ac08-fa9fd90915b5.

Comparison of MRI segmentation techniques for measuring liver cyst volumes in autosomal dominant polycystic kidney disease.

PubMed

Farooq, Zerwa; Behzadi, Ashkan Heshmatzadeh; Blumenfeld, Jon D; Zhao, Yize; Prince, Martin R

To compare MRI segmentation methods for measuring liver cyst volumes in autosomal dominant polycystic kidney disease (ADPKD). Liver cyst volumes in 42 ADPKD patients were measured using region growing, thresholding and cyst diameter techniques. Manual segmentation was the reference standard. Root mean square deviation was 113, 155, and 500 for cyst diameter, thresholding and region growing respectively. Thresholding error for cyst volumes below 500ml was 550% vs 17% for cyst volumes above 500ml (p<0.001). For measuring volume of a small number of cysts, cyst diameter and manual segmentation methods are recommended. For severe disease with numerous, large hepatic cysts, thresholding is an acceptable alternative. Copyright © 2017 Elsevier Inc. All rights reserved.

Noninvasive Classification of Hepatic Fibrosis Based on Texture Parameters From Double Contrast-Enhanced Magnetic Resonance Images

PubMed Central

Bahl, Gautam; Cruite, Irene; Wolfson, Tanya; Gamst, Anthony C.; Collins, Julie M.; Chavez, Alyssa D.; Barakat, Fatma; Hassanein, Tarek; Sirlin, Claude B.

2016-01-01

Purpose To demonstrate a proof of concept that quantitative texture feature analysis of double contrast-enhanced magnetic resonance imaging (MRI) can classify fibrosis noninvasively, using histology as a reference standard. Materials and Methods A Health Insurance Portability and Accountability Act (HIPAA)-compliant Institutional Review Board (IRB)-approved retrospective study of 68 patients with diffuse liver disease was performed at a tertiary liver center. All patients underwent double contrast-enhanced MRI, with histopathology-based staging of fibrosis obtained within 12 months of imaging. The MaZda software program was used to compute 279 texture parameters for each image. A statistical regularization technique, generalized linear model (GLM)-path, was used to develop a model based on texture features for dichotomous classification of fibrosis category (F ≤2 vs. F ≥3) of the 68 patients, with histology as the reference standard. The model's performance was assessed and cross-validated. There was no additional validation performed on an independent cohort. Results Cross-validated sensitivity, specificity, and total accuracy of the texture feature model in classifying fibrosis were 91.9%, 83.9%, and 88.2%, respectively. Conclusion This study shows proof of concept that accurate, noninvasive classification of liver fibrosis is possible by applying quantitative texture analysis to double contrast-enhanced MRI. Further studies are needed in independent cohorts of subjects. PMID:22851409

Possible Contrast Media Reduction with Low keV Monoenergetic Images in the Detection of Focal Liver Lesions: A Dual-Energy CT Animal Study

PubMed Central

Chung, Yong Eun; You, Je Sung; Lee, Hye-Jeong; Lim, Joon Seok; Lee, Hye Sun; Baek, Song-Ee; Kim, Myeong-Jin

2015-01-01

Objective To investigate the feasibility of dual-energy CT for contrast media (CM) reduction in the diagnosis of hypervascular and hypovascular focal liver lesions (FLL). Subjects and Methods The Institutional Animal Care and Use Committee approved this study. VX2 tumors were implanted in two different segments of the liver in 13 rabbits. After 2 weeks, two phase contrast enhanced CT scans including the arterial phase (AP) and portal-venous phase (PVP) were performed three times with 24-hour intervals with three different concentrations of iodine, 300 (I300), 150 (I150) and 75 mg I/mL (I75). The mean HU and standard deviation (SD) were measured in the liver, the hypervascular portion of the VX2 tumor which represented hypervascular tumors, and the central necrotic area of the VX2 tumor which represented hypovascular tumors in 140kVp images with I300 as a reference standard and in monoenergetic images (between 40keV and 140keV) with I150 and I75. The contrast-to-noise ratio (CNR) for FLLs and the ratio of the CNRs (CNRratio) between monoenergetic image sets with I150 and I75, and the reference standard were calculated. Results For hypervascular lesions, the CNRratio was not statistically different from 1.0 between 40keV and 70keV images with I150, whereas the CNRratio was significantly lower than 1.0 in all keV images with I75. For hypovascular lesions, the CNRratio was similar to or higher than 1.0 between 40keV and 80keV with I150 and between 40keV and 70keV with I75. Conclusions With dual-energy CT, the total amount of CM might be halved in the diagnosis of hypervascular FLLs and reduced to one-fourth in the diagnosis of hypovascular FLLs, while still preserving CNRs. PMID:26203652

Non invasive tools for the diagnosis of liver cirrhosis.

PubMed

Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

2014-12-28

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

Non invasive tools for the diagnosis of liver cirrhosis

PubMed Central

Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

2014-01-01

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis. PMID:25561782

Interobserver Agreement for Contrast-Enhanced Ultrasound (CEUS)-Based Standardized Algorithms for the Diagnosis of Hepatocellular Carcinoma in High-Risk Patients.

PubMed

Schellhaas, Barbara; Pfeifer, Lukas; Kielisch, Christian; Goertz, Ruediger Stephan; Neurath, Markus F; Strobel, Deike

2018-06-07

 This pilot study aimed at assessing interobserver agreement with two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.  Focal liver lesions in 55 high-risk patients were assessed independently by three blinded observers with two standardized CEUS algorithms: ESCULAP (Erlanger Synopsis of Contrast-Enhanced Ultrasound for Liver Lesion Assessment in Patients at risk) and ACR-CEUS-LI-RADSv.2016 (American College of Radiology CEUS-Liver Imaging Reporting and Data System). Lesions were categorized according to size and ultrasound contrast enhancement in the arterial, portal-venous and late phase. Interobserver agreement for assessment of enhancement pattern and categorization was compared between both CEUS algorithms. Additionally, diagnostic accuracy for the definitive diagnosis of HCC was compared. Histology and/or CE-MRI and follow-up served as reference standards.  55 patients were included in the study (male/female, 44/ 11; mean age: 65.9 years). 90.9 % had cirrhosis. Histological findings were available in 39/55 lesions (70.9 %). Reference standard of the 55 lesions revealed 48 HCCs, 2 intrahepatic cholangiocellular carcinomas (ICCs), and 5 non-HCC-non-ICC lesions. Interobserver agreement was moderate to substantial for arterial phase hyperenhancement (ĸ = 0.53 - 0.67), and fair to moderate for contrast washout in the portal-venous or late phase (ĸ = 0.33 - 0.53). Concerning the CEUS-based algorithms, the interreader agreement was substantial for the ESCULAP category (ĸ = 0.64 - 0.68) and fair for the CEUS-LI-RADS ® category (ĸ = 0.3 - 0.39). Disagreement between observers was mostly due to different perception of washout.  Interobserver agreement is better for ESCULAP than for CEUS-LI-RADS ® . This is mostly due to the fact that perception of contrast washout varies between different observers. However, interobserver agreement is good for arterial phase hyperenhancement, which is the key diagnostic feature for the diagnosis of HCC with CEUS in the cirrhotic liver. © Georg Thieme Verlag KG Stuttgart · New York.

Liver Volumetry Plug and Play: Do It Yourself with ImageJ

PubMed Central

Dello, Simon A. W. G.; van Dam, Ronald M.; Slangen, Jules J. G.; van de Poll, Marcel C. G.; Bemelmans, Marc H. A.; Greve, Jan Willem W. M.; Beets-Tan, Regina G. H.; Wigmore, Stephen J.

2007-01-01

Background A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon’s desktop. We aimed to assess the accuracy of ImageJ for hepatic CT volumetry. Methods ImageJ was downloaded from http://www.rsb.info.nih.gov/ij/. Preoperative CT scans of 15 patients who underwent liver resection for colorectal cancer liver metastases were retrospectively analyzed. Scans were opened in ImageJ; and the liver, all metastases, and the intended parenchymal transection line were manually outlined on each slice. The area of each selected region, metastasis, resection specimen, and remnant liver was multiplied by the slice thickness to calculate volume. Volumes of virtual liver resection specimens measured with ImageJ were compared with specimen weights and calculated volumes obtained during pathology examination after resection. Results There was an excellent correlation between the volumes calculated with ImageJ and the actual measured weights of the resection specimens (r² = 0.98, p < 0.0001). The weight/volume ratio amounted to 0.88 ± 0.04 (standard error) and was in agreement with our earlier findings using CT-linked radiologic software. Conclusion ImageJ can be used for accurate hepatic CT volumetry on a personal computer. This application brings CT volumetry to the surgeon’s desktop at no expense and is particularly useful in cases of tertiary referred patients, who already have a proper CT scan on CD-ROM from the referring institution. Most likely the discrepancy between volume and weight results from exsanguination of the liver after resection. PMID:17726630

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

PubMed

Henninger, B; Zoller, H; Rauch, S; Schocke, M; Kannengiesser, S; Zhong, X; Reiter, G; Jaschke, W; Kremser, C

2015-05-01

To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Non-invasive assessment of liver fibrosis

PubMed Central

Papastergiou, Vasilios; Tsochatzis, Emmanuel; Burroughs, Andrew K.

2012-01-01

The presence and degree of hepatic fibrosis is crucial in order to make therapeutic decisions and predict clinical outcomes. Currently, the place of liver biopsy as the standard of reference for assessing liver fibrosis has been challenged by the increasing awareness of a number of drawbacks related to its use (invasiveness, sampling error, inter-/intraobserver variability). In parallel with this, noninvasive assessment of liver fibrosis has experienced explosive growth in recent years and a wide spectrum of noninvasive methods ranging from serum assays to imaging techniques have been developed. Some are validated methods, such as the Fibrotest/ Fibrosure and transient elastography in Europe, and are gaining a growing role in routine clinical practice, especially in chronic hepatitis C. Large-scale validation is awaited in the setting of other chronic liver diseases. However, noninvasive tests used to detect significant fibrosis and cirrhosis, the two major clinical endpoints, are not yet at a level of performance suitable for routine diagnostic tests, and there is still no perfect surrogate or method able to completely replace an optimal liver biopsy. This article aims to review current noninvasive tests for the assessment of liver fibrosis and the perspectives for their rational use in clinical practice. PMID:24714123

First Definition of Reference Intervals of Liver Function Tests in China: A Large-Population-Based Multi-Center Study about Healthy Adults

PubMed Central

Zhang, Chuanbao; Guo, Wei; Huang, Hengjian; Ma, Yueyun; Zhuang, Junhua; Zhang, Jie

2013-01-01

Background Reference intervals of Liver function tests are very important for the screening, diagnosis, treatment, and monitoring of liver diseases. We aim to establish common reference intervals of liver function tests specifically for the Chinese adult population. Methods A total of 3210 individuals (20–79 years) were enrolled in six representative geographical regions in China. Analytes of ALT, AST, GGT, ALP, total protein, albumin and total bilirubin were measured using three analytical systems mainly used in China. The newly established reference intervals were based on the results of traceability or multiple systems, and then validated in 21 large hospitals located nationwide qualified by the National External Quality Assessment (EQA) of China. Results We had been established reference intervals of the seven liver function tests for the Chinese adult population and found there were apparent variances of reference values for the variables for partitioning analysis such as gender(ALT, GGT, total bilirubin), age(ALP, albumin) and region(total protein). More than 86% of the 21 laboratories passed the validation in all subgroup of reference intervals and overall about 95.3% to 98.8% of the 1220 validation results fell within the range of the new reference interval for all liver function tests. In comparison with the currently recommended reference intervals in China, the single side observed proportions of out of range of reference values from our study for most of the tests deviated significantly from the nominal 2.5% such as total bilirubin (15.2%), ALP (0.2%), albumin (0.0%). Most of reference intervals in our study were obviously different from that of other races. Conclusion These used reference intervals are no longer applicable for the current Chinese population. We have established common reference intervals of liver function tests that are defined specifically for Chinese population and can be universally used among EQA-approved laboratories located all over China. PMID:24058449

Liver transplant

MedlinePlus

... fully working livers after a successful transplant. The donor liver is transported in a cooled salt-water (saline) ... Liver failure - liver transplant; Cirrhosis - liver transplant Images Donor liver attachment Liver transplant - series References Carrion AF, Martin ...

Determination of metallothionein in biological fluids using enzyme-linked immunoassay with commercial antibody.

PubMed

Milnerowicz, Halina; Bizoń, Anna

2010-01-01

Metallothionein (MT) is a low molecular weight cysteine-rich protein with a number of roles in the pro/antioxidant balance and homeostasis of essential metals, such as zinc and copper, and in the detoxification of heavy metals, such as cadmium and mercury. Until now, detection of metallothionein in biological fluids remained difficult because of a lack of a broadly reactive commercial test. Meaningful comparison of the values of metallothionein concentrations reported by different authors using their specific isolation procedures and different conditions of enzyme-linked immunoassay is difficult due to the absence of a reference material for metallothionein. Therefore in the present study, we describe a quantitative assay for metallothionein in biological fluids such as plasma and urine performed by a direct enzyme-linked immunoassay using a commercially available monoclonal mouse anti-metallothionein clone E9 antibody and commercial standards of metallothionein from rabbit liver and a custom preparation of metallothionein from human liver. The sensitivity of the assay for the standard containing two isoforms MT-I and MT-II from human liver was 140 pg/well. The reactivity of the commercial standards and standards containing two isoforms MT-I and MT-II isolated from human liver in our laboratory with a commercial monoclonal mouse anti-metallothionein clone E9 antibody were similar. This suggests that the described ELISA test can be useful for determination of metallothionein concentration in biological fluids. The concentrations of metallothionein in human plasma, erythrocyte lysate and in urine of smoking and non-smoking healthy volunteers are reported. Tobacco smoking increases the extracellular metallothionein concentration (plasma and urine) but does not affect the intracellular concentration (erythrocyte lysate).

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

PubMed

Stankovic, Zoran; Fink, Jury; Collins, Jeremy D; Semaan, Edouard; Russe, Maximilian F; Carr, James C; Markl, Michael; Langer, Mathias; Jung, Bernd

2015-04-01

We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors. k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS). Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05). k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.

An epizootic of common loons in coastal waters of North Carolina: Concentrations of elemental contaminants and results of necropsies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Augspurger, T.; Franson, J.C.; Converse, K.A.

1998-02-01

A 1993 die-off of common loons (Gavia immer) in the coastal waters of North Carolina was investigated with emphasis on comparing mercury, selenium, arsenic, and lead between birds from the epizootic and reference specimens. Die-off specimens were emaciated but contained no ingested foreign bodies and no lesions suggestive of infectious disease. Results of bacteriology, virology, parasitology, and botulism testing were unremarkable. The geometric mean concentrations (wet weight) of liver mercury and arsenic did not differ between specimens from the die-off and reference loons from the same area that died of other causes. The geometric mean liver selenium concentration of die-offmore » specimens was significantly higher than that of reference loons. Liver lead concentrations were < 0.20 ppm in all but one sample (5.83 ppm). The geometric mean mercury concentration in the primary remiges of die-off specimens was significantly lower than in reference birds. Liver mercury significantly correlated with liver selenium on a molar concentration basis. The authors interpret the range of liver mercury concentrations in birds from the epizootic, similar liver mercury concentrations in reference loons, and higher mercury concentrations in reference loon feathers as evidence that factors other than mercury were primarily responsible for the emaciation diagnosed as the cause of mortality.« less

An epizootic of common loons in coastal waters of North Carolina: Concentrations of elemental contaminants and results of necropsies

USGS Publications Warehouse

Augspurger, Tom; Franson, J. Christian; Converse, Kathryn A.; Spitzer, P.; Miller, E.A.

1998-01-01

A 1993 die-off of common loons (Gavia immer) in the coastal waters of North Carolina was investigated with emphasis on comparing mercury, selenium, arsenic, and lead between birds from the epizootic and reference specimens. Die-off specimens were emaciated but contained no ingested foreign bodies and no lesions suggestive of infectious disease. Results of bacteriology, virology, parasitology, and botulism testing were unremarkable. The geometric mean concentrations (wet weight) of liver mercury (10.9 ppm), and arsenic (0.96 ppm) did not differ between specimens from the die-off and reference loons from the same area that died of other causes. The geometric mean liver selenium concentration of die-off specimens (10.4 ppm) was significantly higher than that of reference loons. Liver lead concentrations were < 0.20 ppm in all but one sample (5.83 ppm). The geometric mean mercury concentration in the primary remiges of die-off specimens (5.44 ppm dry weight) was significantly lower than in reference birds. Liver mercury significantly correlated with liver selenium on a molar concentration basis. We interpret the range of liver mercury concentrations in birds from the epizootic, similar liver mercury concentrations in reference loons, and higher mercury concentrations in reference loon feathers as evidence that factors other than mercury were primarily responsible for the emaciation diagnosed as the cause of mortality.

EFFECT ON PERFUSION VALUES OF SAMPLING INTERVAL OF CT PERFUSION ACQUISITIONS IN NEUROENDOCRINE LIVER METASTASES AND NORMAL LIVER

PubMed Central

Ng, Chaan S.; Hobbs, Brian P.; Wei, Wei; Anderson, Ella F.; Herron, Delise H.; Yao, James C.; Chandler, Adam G.

2014-01-01

Objective To assess the effects of sampling interval (SI) of CT perfusion acquisitions on CT perfusion values in normal liver and liver metastases from neuroendocrine tumors. Methods CT perfusion in 16 patients with neuroendocrine liver metastases were analyzed by distributed parameter modeling to yield tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction, for tumor and normal liver. CT perfusion values for the reference sampling interval of 0.5s (SI0.5) were compared with those of SI datasets of 1s, 2s, 3s and 4s, using mixed-effects model analyses. Results Increases in SI beyond 1s were associated with significant and increasing departures of CT perfusion parameters from reference values at SI0.5 (p≤0.0009). CT perfusion values deviated from reference with increasing uncertainty with increasing SIs. Findings for normal liver were concordant. Conclusion Increasing SIs beyond 1s yield significantly different CT perfusion parameter values compared to reference values at SI0.5. PMID:25626401

High SNR Acquisitions Improve the Repeatability of Liver Fat Quantification Using Confounder-corrected Chemical Shift-encoded MR Imaging

PubMed Central

Motosugi, Utaroh; Hernando, Diego; Wiens, Curtis; Bannas, Peter; Reeder, Scott. B

2017-01-01

Purpose: To determine whether high signal-to-noise ratio (SNR) acquisitions improve the repeatability of liver proton density fat fraction (PDFF) measurements using confounder-corrected chemical shift-encoded magnetic resonance (MR) imaging (CSE-MRI). Materials and Methods: Eleven fat-water phantoms were scanned with 8 different protocols with varying SNR. After repositioning the phantoms, the same scans were repeated to evaluate the test-retest repeatability. Next, an in vivo study was performed with 20 volunteers and 28 patients scheduled for liver magnetic resonance imaging (MRI). Two CSE-MRI protocols with standard- and high-SNR were repeated to assess test-retest repeatability. MR spectroscopy (MRS)-based PDFF was acquired as a standard of reference. The standard deviation (SD) of the difference (Δ) of PDFF measured in the two repeated scans was defined to ascertain repeatability. The correlation between PDFF of CSE-MRI and MRS was calculated to assess accuracy. The SD of Δ and correlation coefficients of the two protocols (standard- and high-SNR) were compared using F-test and t-test, respectively. Two reconstruction algorithms (complex-based and magnitude-based) were used for both the phantom and in vivo experiments. Results: The phantom study demonstrated that higher SNR improved the repeatability for both complex- and magnitude-based reconstruction. Similarly, the in vivo study demonstrated that the repeatability of the high-SNR protocol (SD of Δ = 0.53 for complex- and = 0.85 for magnitude-based fit) was significantly higher than using the standard-SNR protocol (0.77 for complex, P < 0.001; and 0.94 for magnitude-based fit, P = 0.003). No significant difference was observed in the accuracy between standard- and high-SNR protocols. Conclusion: Higher SNR improves the repeatability of fat quantification using confounder-corrected CSE-MRI. PMID:28190853

Radiographic measurement of internal organs in Spix's macaws (Cyanopsitta spixii).

PubMed

Rettmer, Helen; Deb, Amrita; Watson, Ryan; Hatt, Jean-Michel; Hammer, Sven

2011-12-01

Radiology is an important diagnostic instrument in avian medicine, but standard measurement ranges for the objective evaluation of radiographs of birds are rare. To establish radiographic reference ranges for the critically endangered Spix's macaw (Cyanopsitta spixii), we measured radiographic silhouettes of the heart, liver, kidneys, spleen, proventriculus, and keel of the sternum on 29 radiographs taken under standardized conditions in adult and juvenile, clinically healthy birds. Ratios were determined for the proventricular diameter-to-keel height, the width of the heart to the width of the thorax, and for the "hourglass shape" (ratio of the width of the heart to the width of the liver). No significant differences were found between the sexes among the adult birds. Compared with adult birds, juvenile females had a significantly larger heart width (19.8 +/- 1.4 mm versus 21.2 +/- 0.7 mm), ratio of the heart width to the thorax width (0.86 +/- 0.08 versus 0.94 +/- 0.09), and horizontal width of the spleen (7.7 +/- 0.6 mm versus 8.5 +/- 0.4 mm). Results of radiographic measurements in the Spix's macaws were comparable to those published from other psittacine species. These reference ranges will facilitate a more objective radiographic evaluation of captive Spix's macaws.

Exploratory use of cardiovascular magnetic resonance imaging in liver transplantation: a one-stop shop for preoperative cardiohepatic evaluation.

PubMed

Reddy, Sahadev T; Thai, Ngoc L; Fakhri, Asghar A; Oliva, Jose; Tom, Kusum B; Dishart, Michael K; Doyle, Mark; Yamrozik, June A; Williams, Ronald B; Grant, Saundra B; Poydence, Jacqueline; Shah, Moneal; Singh, Anil; Nathan, Swami; Biederman, Robert W W

2013-11-15

Preoperative cardiovascular risk stratification in orthotopic liver transplantation candidates has proven challenging due to limitations of current noninvasive modalities. Additionally, the preoperative workup is logistically cumbersome and expensive given the need for separate cardiac, vascular, and abdominal imaging. We evaluated the feasibility of a "one-stop shop" in a magnetic resonance suite, performing assessment of cardiac structure, function, and viability, along with simultaneous evaluation of thoracoabdominal vasculature and liver anatomy. In this pilot study, patients underwent steady-state free precession sequences and stress cardiac magnetic resonance (CMR), thoracoabdominal magnetic resonance angiography, and abdominal magnetic resonance imaging (MRI) on a standard MRI scanner. Pharmacologic stress was performed using regadenoson, adenosine, or dobutamine. Viability was assessed using late gadolinium enhancement. Over 2 years, 51 of 77 liver transplant candidates (mean age, 56 years; 35% female; mean Model for End-stage Liver Disease score, 10.8; range, 6-40) underwent MRI. All referred patients completed standard dynamic CMR, 98% completed stress CMR, 82% completed late gadolinium enhancement for viability, 94% completed liver MRI, and 88% completed magnetic resonance angiography. The mean duration of the entire study was 72 min, and 45 patients were able to complete the entire examination. Among all 51 patients, 4 required follow-up coronary angiography (3 for evidence of ischemia on perfusion CMR and 1 for postoperative ischemia), and none had flow-limiting coronary disease. Nine proceeded to orthotopic liver transplantation (mean 74 days to transplantation after MRI). There were six ascertained mortalities in the nontransplant group and one death in the transplanted group. Explant pathology confirmed 100% detection/exclusion of hepatocellular carcinoma. No complications during CMR examination were encountered. In this proof-of-concept study, it appears feasible to perform a comprehensive, efficient, and safe preoperative liver transplant imaging in a CMR suite-a one-stop shop, even in seriously ill patients.

Point shear wave speed measurement in differentiating benign and malignant focal liver lesions.

PubMed

Dong, Yi; Wang, Wen-Ping; Xu, Yadan; Cao, Jiaying; Mao, Feng; Dietrich, Cristoph F

2017-06-26

To investigate the value of ElastPQ measurement for differential diagnosis of benign and malignant focal liver lesions (FLLs) by using histologic results as a reference standard. A total of 154 patients were included. ElastPQ measurement was performed for each lesion in which the shear wave speed (SWS) was measured. The difference in SWS and SWS ratio of FLL to surrounding liver were evaluated, and the cut off value was investigated. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance. Histology as a gold standard was obtained by surgery in all patients. A total of 154 lesions including 129 (83.7 %) malignant FLLs and 25 (16.3 %) benign ones were analysed. The SWS of malignant and benign FLLs was significantly different, 2.77±0.68 m/s and 1.57±0.55 m/s (p<0.05). The SWS ratio of each FLL to surrounding liver parenchyma was 2.23±0.49 for malignant and 1.14±0.36 for benign FLLs (p<0.05). The cut off value for differential diagnosis was 2.06 m/s for SWS and 1.67 for SWS ratio.  ElastPQ measurement provides reliable quantitative stiffness information of FLLs and may be helpful in the differential diagnosis between malignant and benign FLLs.

Non-invasive assessment of liver fibrosis using two-dimensional shear wave elastography in patients with autoimmune liver diseases

PubMed Central

Zeng, Jie; Huang, Ze-Ping; Zheng, Jian; Wu, Tao; Zheng, Rong-Qin

2017-01-01

AIM To determine the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in patients with autoimmune liver diseases (AILD) using liver biopsy as the reference standard. METHODS Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values. RESULTS The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and 16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%. CONCLUSION 2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages. PMID:28765706

Non-invasive assessment of liver fibrosis using two-dimensional shear wave elastography in patients with autoimmune liver diseases.

PubMed

Zeng, Jie; Huang, Ze-Ping; Zheng, Jian; Wu, Tao; Zheng, Rong-Qin

2017-07-14

To determine the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE) for the non-invasive assessment of liver fibrosis in patients with autoimmune liver diseases (AILD) using liver biopsy as the reference standard. Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic (ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values. The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 9.7 kPa, 13.2 kPa and 16.3 kPa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis, and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%. 2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages.

EROD activity and biliary fluorescence in Schroederichthys chilensis (Guichenot 1848): biomarkers of PAH exposure in coastal environments of the South Pacific Ocean.

PubMed

Fuentes-Rios, Daniel; Orrego, Rodrigo; Rudolph, Anny; Mendoza, Gonzalo; Gavilán, Juan F; Barra, Ricardo

2005-10-01

Schroederichthys chilensis is a common shark that lives in Chilean coastal environments. In this work, the relationship between liver 7-ethoxyresorufin-O-deethylase dealkylation (EROD) activity and Fluorescent Aromatic Compounds (FAC) in bile of S. chilensis sampled in three bays with different degrees of pollution were performed including a reference area. Sixty individuals were collected, 20 for each site; (10 males and 10 females per site) livers and bile samples were obtained and immediately frozen. EROD activity and FAC were measured according to three standard methods. EROD activity and FAC were higher in polluted areas than in the reference area. Synchronous Fluorescence Spectra of the bile from the fish collected at the most polluted area showed a peak at 347nm representing a metabolite corresponding to 1-hydroxypyrene. The low EROD activity in the reference area is likely related to the low level of PAH in sediments. We propose that this species is a good indicator of exposure to FACs, since it presents a series of characteristics that make it suitable for monitoring PAH exposure in coastal zones.

[A case of malignant lymphoma successfully diagnosed using Sasada transbronchial angled biopsy forceps].

PubMed

Komori, Chika; Sasada, Shinji; Okamoto, Norio; Kawahara, Kunimitsu; Uehara, Nobuko; Shimada, Kazutaka; Kuhara, Hanako; Terada, Haruko; Tsujino, Kazuyuki; Matsunashi, Tatsuro; Minami, Toshiyuki; Suzuki, Hidekazu; Kobayashi, Masashi; Hirashima, Tomonori; Matsui, Kaoru; Kawase, Ichiro; Kusunoki, Yoko

2009-01-01

A 68-year-old man was referred to our hospital due to general fatigue, fever and weight loss. His chest radiograph showed a nodule (2.8 cm) in the right middle lobe. Computed tomography and positron emission tomography showed multiple metastases to the bone, liver and lymph nodes. The lung nodule was not accessible by standard transbronchial forceps. However, biopsy specimens obtained using Sasada Transbronchial Angled Biopsy Forceps (STAF) pathologically confirmed the diagnosis of malignant lymphoma. We report the case, and discuss the utility of STAF for lung lesions that are difficult to access with standard forceps.

Valproic acid and nonalcoholic fatty liver disease: A possible association?

PubMed Central

Farinelli, Edoardo; Giampaoli, David; Cenciarini, Anja; Cercado, Ephraim; Verrotti, Alberto

2015-01-01

Valproic acid (VPA) is one of the most prescribed drugs in children with newly diagnosed epilepsy. Weight gain and obesity have been observed as side effects of VPA. These are often linked with other metabolic disturbances such as development of insulin resistance, dyslipidemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD). NAFLD refers to a group of liver disorders with marked hepatic steatosis. It is associated with an increased incidence of cardiovascular diseases and overall reduced life expectancy. NAFLD occurs in 20%-25% of the general population and it is known to be the most common cause of chronic liver disease. NAFLD therefore represents a major public health issue worldwide. This study reviews and summarizes relevant literature that supports the existence of an association between VPA therapy and the development of NAFLD in children. Long-term VPA-therapy appears to be associated with an increased risk of developing NAFLD. Further studies are needed to clarify the pathogenic mechanisms that lie behind this association and to standardize the options for the use of this drug in overweight patients and in those with risks for developing MetS and NAFLD. PMID:26019740

Gallium-68 DOTATOC PET/CT In Vivo Characterization of Somatostatin Receptor Expression in the Prostate

PubMed Central

Gajić, Milan M.; Obradović, Vladimir B.; Baum, Richard P.

2014-01-01

Abstract Aim: The aim was to investigate somatostatin receptor (sstr) expression in normal prostate by determining the maximum standardized uptake value (SUVmax) of 68Ga-DOTATOC PET/CT in neuroendocrine tumor (NET) patients, without NET involvement of the prostate gland, for establishing the reference standard. Methods: Sixty-four NET patients underwent 68Ga-DOTATOC PET/CT. SUVmax of the prostate gland, normal liver, testes, and gluteus muscles were evaluated. The prostate gland size was measured. Statistical analysis was performed using dedicated software (SPSS13). Results: Mean/median 68Ga-DOTATOC SUVmax values were as follows: normal prostate 2.6±0.0, slightly enlarged prostate 4.2±1.6, prostatic hypertrophy 4.9±1.6, prostatic hyperplasia 5.0±1.5, prostate cancer 9.5±2.1, normal liver 7.3±1.8, testes 1.8±0.5, and gluteus 1.0±0.2. The normal prostate gland had three times less sstr expression than normal liver tissue. Strong correlation was found between patient age and sstr expression in prostate/prostate size. No significant difference existed in sstr expression between prostatic hypertrophy and hyperplasia. Much higher sstr expression was found in prostatic cancer compared with normal prostate. Conclusion: 68Ga-DOTATOC PET/CT defines the baseline sstr uptake in prostate not affected by NET (significantly lower than in the liver). Higher values were established in prostatic hyperplasia and hypertrophy. Only concomitant prostate cancer was associated with higher SUVmax in comparison with non-neoplastic liver. PMID:24450327

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

PubMed

Kliemann, Dimas A; Wolff, Fernando H; Tovo, Cristiane V; Alencastro, Paulo R; Ikeda, Maria L R; Brandão, Ajácio B M; Barcellos, Nêmora; Fuchs, Sandra C

2016-01-01

The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

New method for assessing liver fibrosis based on acoustic radiation force impulse: a special reference to the difference between right and left liver.

PubMed

Toshima, Takeo; Shirabe, Ken; Takeishi, Kazuki; Motomura, Takashi; Mano, Youhei; Uchiyama, Hideaki; Yoshizumi, Tomoharu; Soejima, Yuji; Taketomi, Akinobu; Maehara, Yoshihiko

2011-05-01

Virtual touch tissue quantification (VTTQ) based on acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive bedside method for the assessment of liver stiffness. In this study, we examined the diagnostic performance of ARFI imaging in 103 patients, focusing on the difference in VTTQ values between the right and left liver lobes. We evaluated VTTQ values of the right and left lobes in 79 patients with chronic liver disease who underwent histological examination of liver fibrosis and in 24 healthy volunteers. The diagnostic accuracy of VTTQ was compared with several serum markers, including hyaluronic acid, type 4 collagen, and aspartate transaminase to platelet ratio index. The VTTQ values (meters per second) in the right and left lobes were 1.61 ± 0.51 and 1.90 ± 0.68, respectively, and the difference was statistically significant (P < 0.0001). The VTTQ values in both liver lobes were correlated significantly with histological fibrosis grades (P < 0.001). The standard deviations of the VTTQ values in the right lobe were significantly lower than those in the left lobe (P < 0.001). The area under the receiver-operating characteristic curve for the diagnosis of fibrosis (F ≥ 3) using VTTQ values in both liver lobes was superior to serum markers, especially in the right lobe. VTTQ is an accurate and reliable tool for the assessment of liver fibrosis. VTTQ of the right lobe was more accurate for diagnosing liver fibrosis than in the left lobe.

Additive value of non-contrast MRA in the preoperative evaluation of potential liver donors.

PubMed

Luk, Lyndon; Shenoy-Bhangle, Anuradha S; Jimenez, Guillermo; Ahmed, Firas S; Prince, Martin R; Samstein, Benjamin; Hecht, Elizabeth M

The purpose of this study is to compare diagnostic quality, inter-observer variability and agreement of non-contrast enhanced MRA (NC-MRA) with contrast-enhanced MRA (CE-MRA) in the evaluation of hepatic arterial anatomy. 20 potential liver donors were included in this retrospective study. NC-MRA, CE-MRA and combined data sets were randomized and reviewed by two readers. Reference standard was consensus by two senior radiologists using all data including CTA. There was no difference in IQ or diagnostic confidence between NC-MRA, CE-MRA or combined data for either reader but the arterial origin of segment IV was successfully identified on NC-MRA when CE-MRA was suboptimal. Copyright © 2016 Elsevier Inc. All rights reserved.

Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study

NASA Astrophysics Data System (ADS)

Mahmoud, Ahmed M.; Ding, Xuan; Dutta, Debaditya; Singh, Vijay P.; Kim, Kang

2014-02-01

Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ˜3 s and ˜9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (-0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (-0.124 ± 0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.

Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study

PubMed Central

Mahmoud, Ahmed M.; Ding, Xuan; Dutta, Debaditya; Singh, Vijay P.; Kim, Kang

2014-01-01

Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer, and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using ultrasound-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n=10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n=10) with low fat content (4.8± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ~3 s and ~9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (−0.065±0.079%) were significantly (p<0.05) higher than those measured in control livers (−0.124±0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis. PMID:24487698

Standardized Evaluation of Candidates Before Liver Transplantation With the Transplant Evaluation Rating Scale.

PubMed

Erim, Yesim; Scheel, Jennifer; Beckmann, Mingo; Klein, Christian-Georg; Paul, Andreas

The Transplant Evaluation Rating Scale (TERS) was developed to provide a standardized evaluation of the psychosocial functioning of patients, before transplantation. Yet, the first 2 items of the TERS are based on psychiatric diagnoses referring to Diagnostic and Statistical Manual (DSM)-III-R, which leads to a duplication of disorder-specific and symptom-specific contents, that makes it complex to rate. Moreover, the TERS has not been updated to DSM revisions and DSM is not used for the official clinical routine documentation in several European countries. The objective of this study was, therefore, to investigate the psychometric properties of a diagnoses-corrected version of the TERS (items 1 and 2 omitted). In 85 patients awaiting liver transplantation, the discrimination capacities, predictive value, convergent validity, and interrater reliability of the original version (TERS10) and the diagnoses-corrected version (TERS8) were analyzed. In both versions, patients with psychiatric diagnoses (69.4%) exhibited significantly higher TERS mean values than patients without psychiatric disorders. This also held for patients who were temporarily not found eligible for transplantation in the psychosocial evaluation (25.9%) compared with patients who were eligible for listing for transplantation. Furthermore, the area under the curve was >0.90 for both versions and a cutoff of 32.25 is suggested for TERS8 (sensitivity of 90.9% and specificity of 87.3%). Our results substantiate good psychometric properties of the revised (diagnoses corrected) TERS, which is of great benefit for standardized psychosocial evaluation before liver transplantation. Further, validation of TERS8 and its cutoff in other samples of (liver) transplantation patients is needed. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Determination of non-ortho polychlorinated biphenyls in environmental Standard Reference Materials.

PubMed

Brubaker, W W; Schantz, M M; Wise, S A

2000-07-01

The concentrations of three non-ortho ("coplanar") polychlorinated biphenyls, 3,3',4,4'-tetrachlorobiphenyl (IUPAC PCB 77), 3,3',4,4',5-pentachlorobiphenyl (IUPAC PCB 126), and 3,3',4,4',5,5'-hexachlorobiphenyl (IUPAC PCB 169), were determined in five NIST Standard Reference Materials (SRMs) of environmental and biological interest. The measured levels were approximately between (0.2 to 1.3) ng/g in SRM 1588a (Organics in Cod Liver Oil), (0.3 to 9) ng/g in SRM 1944 (New York/New Jersey Waterway Sediment), (0.2 to 0.4) ng/g in SRM 1945 (Organics in Whale Blubber), (1 to 18) ng/g in SRM 2974 (Organics in Freeze-dried Mussel Tissue [Mytilus edulis]), and (0.1 to 0.4) ng/g in candidate SRM 1946 (Lake Superior Fish Tissue). PCB 169 was present at < 0.1 ng/g in SRMs 1944 and 2974.

Application of classification trees for the qualitative differentiation of focal liver lesions suspicious for metastasis in gadolinium-EOB-DTPA-enhanced liver MR imaging.

PubMed

Schelhorn, J; Benndorf, M; Dietzel, M; Burmeister, H P; Kaiser, W A; Baltzer, P A T

2012-09-01

To evaluate the diagnostic accuracy of qualitative descriptors alone and in combination for the classification of focal liver lesions (FLLs) suspicious for metastasis in gadolinium-EOB-DTPA-enhanced liver MR imaging. Consecutive patients with clinically suspected liver metastases were eligible for this retrospective investigation. 50 patients met the inclusion criteria. All underwent Gd-EOB-DTPA-enhanced liver MRI (T2w, chemical shift T1w, dynamic T1w). Primary liver malignancies or treated lesions were excluded. All investigations were read by two blinded observers (O1, O2). Both independently identified the presence of lesions and evaluated predefined qualitative lesion descriptors (signal intensities, enhancement pattern and morphology). A reference standard was determined under consideration of all clinical and follow-up information. Statistical analysis besides contingency tables (chi square, kappa statistics) included descriptor combinations using classification trees (CHAID methodology) as well as ROC analysis. In 38 patients, 120 FLLs (52 benign, 68 malignant) were present. 115 (48 benign, 67 malignant) were identified by the observers. The enhancement pattern, relative SI upon T2w and late enhanced T1w images contributed significantly to the differentiation of FLLs. The overall classification accuracy was 91.3 % (O1) and 88.7 % (O2), kappa = 0.902. The combination of qualitative lesion descriptors proposed in this work revealed high diagnostic accuracy and interobserver agreement in the differentiation of focal liver lesions suspicious for metastases using Gd-EOB-DTPA-enhanced liver MRI. © Georg Thieme Verlag KG Stuttgart · New York.

Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

PubMed Central

Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

2011-01-01

Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

Impact of missing attenuation and scatter corrections on 99m Tc-MAA SPECT 3D dosimetry for liver radioembolization using the patient relative calibration methodology: A retrospective investigation on clinical images.

PubMed

Botta, Francesca; Ferrari, Mahila; Chiesa, Carlo; Vitali, Sara; Guerriero, Francesco; Nile, Maria Chiara De; Mira, Marta; Lorenzon, Leda; Pacilio, Massimiliano; Cremonesi, Marta

2018-04-01

To investigate the clinical implication of performing pre-treatment dosimetry for 90 Y-microspheres liver radioembolization on 99m Tc-MAA SPECT images reconstructed without attenuation or scatter correction and quantified with the patient relative calibration methodology. Twenty-five patients treated with SIR-Spheres ® at Istituto Europeo di Oncologia and 31 patients treated with TheraSphere ® at Istituto Nazionale Tumori were considered. For each acquired 99m Tc-MAA SPECT, four reconstructions were performed: with attenuation and scatter correction (AC_SC), only attenuation (AC_NoSC), only scatter (NoAC_SC) and without corrections (NoAC_NoSC). Absorbed dose maps were calculated from the activity maps, quantified applying the patient relative calibration to the SPECT images. Whole Liver (WL) and Tumor (T) regions were drawn on CT images. Injected Liver (IL) region was defined including the voxels receiving absorbed dose >3.8 Gy/GBq. Whole Healthy Liver (WHL) and Healthy Injected Liver (HIL) regions were obtained as WHL = WL - T and HIL = IL - T. Average absorbed dose to WHL and HIL were calculated, and the injection activity was derived following each Institute's procedure. The values obtained from AC_NoSC, NoAC_SC and NoAC_NoSC images were compared to the reference value suggested by AC_SC images using Bland-Altman analysis and Wilcoxon paired test (5% significance threshold). Absorbed-dose maps were compared to the reference map (AC_SC) in global terms using the Voxel Normalized Mean Square Error (%VNMSE), and at voxel level by calculating for each voxel the normalized difference with the reference value. The uncertainty affecting absorbed dose at voxel level was accounted for in the comparison; to this purpose, the voxel counts fluctuation due to Poisson and reconstruction noise was estimated from SPECT images of a water phantom acquired and reconstructed as patient images. NoAC_SC images lead to activity prescriptions not significantly different from the reference AC_SC images; the individual differences (<0.1 GBq for all IEO patients, <0.6 GBq for all but one INT patients) were comparable to the uncertainty affecting activity measurement. AC_NoSC and NoAC_NoSC images, instead, yielded significantly different activity prescriptions and wider 95% confidence intervals in the Bland-Altman analysis. Concerning the absorbed dose map, AC_NoSC images had the smallest %VNMSE value and the highest fraction of voxels differing less than 2 standard deviations from AC_SC. The patient relative calibration methodology can compensate for the missing attenuation correction when performing healthy liver pre-treatment dosimetry: safe treatments can be planned even on NoAC_SC images, suggesting activities comparable to AC_SC images. Scatter correction is recommended due to its heavy impact on healthy liver dosimetry. © 2018 American Association of Physicists in Medicine.

The use of a single multielement standard for trace analysis in biological materials by external beam PIXE

NASA Astrophysics Data System (ADS)

Biswas, S. K.; Khaliquzzaman, M.; Islam, M. M.; Khan, A. H.

1984-04-01

The validity of the use of a single multielement standard for mass calibration in thick-target external beam PIXE analysis of biological materials has been investigated. In this study, the NBS orchard leaf, SRM 1571, was used as the basic standard for trace element analysis in other biological materials. Using the present procedure, the concentrations of K, Ca, Mn, Fe, Ni, Cu, Zn, Br, Rb and Sr were determined in several NBS reference materials such as bovine liver, spinach, rice flour, etc., generally in 20 μC irradiations with 2.0 MeV protons. The analytical results are compared with certified values of the NBS as well as with other measurements and the sources of errors are discussed.

Kinetic analysis of contralateral liver hypertrophy after radioembolization of primary and metastatic liver tumors.

PubMed

Orcutt, Sonia T; Abuodeh, Yazan; Naghavi, Arash; Frakes, Jessica; Hoffe, Sarah; Kis, Bela; Anaya, Daniel A

2018-05-01

Radioembolization induces liver hypertrophy, although the extent and rate of hypertrophy are unknown. Our goal was to examine the kinetics of contralateral liver hypertrophy after transarterial radioembolization. A retrospective study (2010-2014) of treatment-naïve patients with primary/secondary liver malignancies undergoing right lobe radioembolization was performed. Computed tomography volumetry was performed before and 1, 3, and 6 months after radioembolization. Outcomes of interest were left lobe (standardized future liver remnant) degree of hypertrophy, kinetic growth rate, and ability to reach goal standardized future liver remnant ≥40%. Medians were compared with the Kruskall-Wallis test. Time to event analysis was used to estimate time to reach goal standardized future liver remnant. In the study, 25 patients were included. At 1, 3, and 6 months, median degree of hypertrophy was 4%, 8%, and 12% (P < .001), degree of hypertrophy relative to baseline future liver remnants was 11%, 17%, and 31% (P = .015), and kinetic growth rate was 0.8%, 0.5%, and 0.4%/week (P = .002). In patients with baseline standardized future liver remnant <40% (N= 16), median time to reach standardized future liver remnant ≥40% was 7.3 months, with 75% accomplishing standardized future liver remnant ≥40% at 8.2 months. Radioembolization induces hypertrophy of the contralateral lobe to a similar extent as existing methods, although at a lower rate. The role of radioembolization as a dual therapy (neoadjuvant and hypetrophy-inducing) for selected patients needs to be studied. (Surgery 2017;160:XXX-XXX.). Copyright © 2017 Elsevier Inc. All rights reserved.

A standardized safe hepatectomy; selective Glissonean transection using endolinear stapling devices.

PubMed

Fujii, Masahiko; Shimada, Mitsuo; Satoru, Imura; Morine, Yuji; Ikemoto, Tetsuya; Soejima, Yuji

2007-01-01

Selective clamping of Glisson's pedicle at the hilum is effective for systematized hepatectomy. Because of the development of stapling devices, a Glissonean transection using a surgical stapler has been used widely. However, the risk of accidental stapling of the biliary confluence still remains. In this paper we report about a case that underwent selective Glissonean transection using an endolinear stapling device. We used this standardized technique in five patients without any major complications. The particular case to which we refer was a 71-year-old woman with hepatocellular carcinoma in the right lobe. The anterior and posterior branches of Glisson's pedicle were independently divided using an endolinear stapling device. The right hepatic lobectomy was achieved with little bleeding and in addition there was a shortened operation time and the postoperative course was uneventful. In the patient with liver cirrhosis, postoperative complications often related to liver failure. We herein advocate a standardized safe hepatectomy using endolinear stapling devices. We believe that the shortened operative time and decreased risk of complications by selective Glissonean transection as well as hepatic vein transection using stapling devices contribute to the improved short-term outcome.

Clinical outcomes for patients with liver-limited metastatic colorectal cancer: Arguing the case for specialist hepatobiliary multidisciplinary assessment.

PubMed

Thillai, K; Repana, D; Korantzis, I; Kane, P; Prachalias, A; Ross, P

2016-09-01

In patients with liver-limited metastatic colorectal cancer, hepatic resection can offer a significant survival benefit over systemic therapy alone. Specialist hepatobiliary multidisciplinary meetings are currently believed to provide the best forum to discuss the management for these patients. A retrospective analysis was undertaken of patients diagnosed with liver-limited metastatic colorectal cancer over 6 months within a cancer network in the United Kingdom. In addition, patients who were diagnosed but not referred to the hepatobiliary meeting were discussed within a virtual multi-disciplinary setting. Contributors were blinded and proposed management recorded. 159 newly diagnosed patients with liver-limited metastatic colorectal cancer were identified. 68 (43%) were referred at initial diagnosis and 38 (24%) referred following systemic treatment. 35 (51%) who were discussed at baseline underwent a subsequent hepatectomy or radiofrequency ablation, as did 18 (47%) patients referred after chemotherapy. Of the remaining 53 (33%) patients not referred, imaging was available for 31 (58%). Decisions regarding potential liver-directed therapy were discussed within a multi-disciplinary setting. 13 (42%) were identified as resectable or potentially resectable and 11 (36%) may have been suitable for a clinical trial. In reality, none of these 31 patients (100%) underwent surgery or ablation. Whilst the majority of patients with liver-limited metastatic colorectal cancer were referred appropriately, this study demonstrates that a significant number with potentially resectable disease are not being discussed at specialist meetings. A review of all diagnosed cases would ensure that an increased number of patients are offered hepatic resection or ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Measurement of the status of trace elements in cattle using liver biopsy samples].

PubMed

Ouweltjes, W; de Zeeuw, A C; Moen, A; Counotte, G H M

2007-02-01

Serum, plasma, or urine samples are usually used for the measurement of the trace elements copper; zinc, iron, selenium, because these samples are easy to obtain; however; these samples are not always appropriate. For example, it is not possible to measure molybdenum, the major antagonist of copper; in blood or urine. Therefore measurement of trace elements in liver tissue is considered the gold standard. For the assessment of selenium the method of choice remains determination of glutathion peroxidase in erythrocytes and for the assessment of magnesium determination of magnesium in urine. We determined the accuracy and repeatability of measuring trace elements in liver biopsies and whole liver homogenates. The levels of trace elements measured were similar in both preparations (92% agreement). Liver biopsy in live animals is a relatively simple procedure but not common in The Netherlands. Reference levels of trace elements, classified as too low, low, adequate, high, and too high, were established on the basis of our research and information in the literature. In a second study we investigated the practical aspects of obtaining liver tissue samples and their use. Samples were collected from cattle on a commercial dairy farm. Liver biopsy provided additional information to that obtained from serum and urine samples. We prepared a biopsy protocol and a test package, which we tested on 14 farms where an imbalance of trace minerals was suspected. Biopsy samples taken from 4 to 6 animals revealed extreme levels of trace elements.

Potential protective effect of honey against paracetamol-induced hepatotoxicity.

PubMed

Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

2012-11-01

Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

Small animal magnetic resonance imaging: an efficient tool to assess liver volume and intrahepatic vascular anatomy.

PubMed

Melloul, Emmanuel; Raptis, Dimitri A; Boss, Andreas; Pfammater, Thomas; Tschuor, Christoph; Tian, Yinghua; Graf, Rolf; Clavien, Pierre-Alain; Lesurtel, Mickael

2014-04-01

To develop a noninvasive technique to assess liver volumetry and intrahepatic portal vein anatomy in a mouse model of liver regeneration. Fifty-two C57BL/6 male mice underwent magnetic resonance imaging (MRI) of the liver using a 4.7 T small animal MRI system after no treatment, 70% partial hepatectomy (PH), or selective portal vein embolization. The protocol consisted of the following sequences: three-dimensional-encoded spoiled gradient-echo sequence (repetition time per echo time 15 per 2.7 ms, flip angle 20°) for volumetry, and two-dimensional-encoded time-of-flight angiography sequence (repetition time per echo time 18 per 6.4 ms, flip angle 80°) for vessel visualization. Liver volume and portal vein segmentation was performed using a dedicated postprocessing software. In animals with portal vein embolization, portography served as reference standard. True liver volume was measured after sacrificing the animals. Measurements were carried out by two independent observers with subsequent analysis by the Cohen κ-test for interobserver agreement. MRI liver volumetry highly correlated with the true liver volume measurement using a conventional method in both the untreated liver and the liver remnant after 70% PH with a high interobserver correlation coefficient of 0.94 (95% confidence interval, 0.80-0.98 for untreated liver [P < 0.001] and 0.90-0.97 after 70% PH [P < 0.001]). The diagnostic accuracy of magnetic resonance angiography for the occlusion of one branch of the portal vein was 0.95 (95% confidence interval, 0.84-1). The level of agreement between the two observers for the description of intrahepatic vascular anatomy was excellent (Cohen κ value = 0.925). This protocol may be used for noninvasive liver volumetry and visualization of portal vein anatomy in mice. It will serve the dynamic study of new strategies to enhance liver regeneration in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

[First clinical experience with extended planning and navigation in an interventional MRI unit].

PubMed

Moche, M; Schmitgen, A; Schneider, J P; Bublat, M; Schulz, T; Voerkel, C; Trantakis, C; Bennek, J; Kahn, T; Busse, H

2004-07-01

To present an advanced concept for patient-based navigation and to report on our first clinical experience with interventions in the cranium, of soft-tissue structures (breast, liver) and in the musculoskeletal system. A PC-based navigation system was integrated into an existing interventional MRI environment. Intraoperatively acquired 3D data were used for interventional planning. The information content of these reference data was increased by integration of additional image modalities (e. g., fMRI, CT) and by color display of areas with early contrast media enhancement. Within 18 months, the system was used in 123 patients undergoing interventions in different anatomic regions (brain: 64, paranasal sinus: 9, breast: 20, liver: 17, bone: 9, muscle: 4). The mean duration of 64 brain interventions was compared with that of 36 procedures using the scanner's standard navigation. In contrast with the continuous scanning mode of the MR system (0.25 fps), the higher quality as well as the real time display (4 fps) of the MR images reconstructed from the 3D reference data allowed adequate hand-eye coordination. With our system, patient movement and tissue shifts could be immediately detected intraoperatively, and, in contrast to the standard procedure, navigation safely resumed after updating the reference data. The navigation system was characterized by good stability, efficient system integration and easy usability. Despite additional working steps still to be optimized, the duration of the image-guided brain tumor resections was not significantly longer. The presented system combines the advantage of intraoperative MRI with established visualization, planning, and real time capabilities of neuronavigation and can be efficiently applied in a broad range of non-neurosurgical interventions.

Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis.

PubMed

Lee, Hyo Young; Jun, Dae Won; Kim, Hyun Jung; Oh, Hyunwoo; Saeed, Waqar Khalid; Ahn, Hyeongsik; Cheung, Ramsey C; Nguyen, Mindie H

2018-03-20

A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91). Ezetimibe decreased NAS without improving hepatic steatosis.

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

PubMed

Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

2018-04-01

Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Noninvasive Assessment of Liver Fibrosis Stage Using Ultrasound-Based Shear Wave Velocity Measurements and Serum Algorithms in Patients With Viral Hepatitis B: A Retrospective Cohort Study.

PubMed

Liu, Jianxue; Zhao, Junzhi; Zhang, Yaoren; Ji, Yonghao; Lin, Shumei; Dun, Guoliang; Guo, Sujuan

2017-02-01

Liver biopsy remains the reference standard for the assessment of liver fibrosis, but this procedure is invasive and can lead to complications. Thus, studies to determine the optimal noninvasive test are warranted. This study compared several noninvasive tests and their combinations for evaluating liver fibrosis stages in patients with chronic hepatitis B. The shear wave velocity (SWV) and laboratory indicators were collected from 174 patients with chronic hepatitis B. Formulas were applied to calculate the serum fibrosis model, including the aspartate aminotransaminase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and aspartate aminotransferase-to-alanine aminotransferase ratio (AAR). The diagnostic performance of all noninvasive tests was assessed in comparison with percutaneous liver biopsy, based on a receiver operating characteristic curve analysis. The SWV (area under the receiver operating characteristic curve [AUC], 0.82) and APRI (AUC = 0.77) performed better than the FIB-4 (AUC = 0.62), and the AAR (AUC = 0.47) was not suitable for evaluating substantial liver fibrosis (stage ≥F2). The SWV (AUC = 0.96) was the best indicator, being superior to the APRI (AUC = 0.75) and FIB-4 (AUC = 0.74), and the AAR (AUC = 0.45) was not suitable for assessing cirrhosis (F4). Combining the SWV and APRI, the AUC improved to 0.85 for substantial liver fibrosis, and the sensitivity increased to 100% for cirrhosis. The SWV, APRI, and FIB-4 were valid tests for evaluating substantial liver fibrosis and cirrhosis. The combination of these tests with several noninvasive indicators is expected to enhance the assessment of liver fibrosis stages. © 2016 by the American Institute of Ultrasound in Medicine.

Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study.

PubMed

Ferraioli, Giovanna; Tinelli, Carmine; Dal Bello, Barbara; Zicchetti, Mabel; Filice, Gaetano; Filice, Carlo

2012-12-01

Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively. The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥ F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information. Copyright © 2012 American Association for the Study of Liver Diseases.

Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents

PubMed Central

Di Martino, Michele; Pacifico, Lucia; Bezzi, Mario; Di Miscio, Rossella; Sacconi, Beatrice; Chiesa, Claudio; Catalano, Carlo

2016-01-01

AIM To establish a threshold value for liver fat content between healthy children and those with non-alcoholic fatty liver disease (NAFLD) by using magnetic resonance imaging (MRI), with liver biopsy serving as a reference standard. METHODS The study was approved by the local ethics committee, and written informed consent was obtained from all participants and their legal guardians before the study began. Twenty-seven children with NAFLD underwent liver biopsy to assess the presence of nonalcoholic steatohepatitis. The assessment of liver fat fraction was performed using MRI, with a high field magnet and 2D gradient-echo and multiple-echo T1-weighted sequence with low flip angle and single-voxel point-resolved ¹H MR-Spectroscopy (¹H-MRS), corrected for T1 and T2* decays. Receiver operating characteristic curve analysis was used to determine the best cut-off value. Lin coefficient test was used to evaluate the correlation between histology, MRS and MRI-PDFF. A Mann-Whitney U-test and multivariate analysis were performed to analyze the continuous variables. RESULTS According to MRS, the threshold value between healthy children and those with NAFLD is 6%; using MRI-PDFF, a cut-off value of 3.5% is suggested. The Lin analysis revealed a good fit between the histology and MRS as well as MRI-PDFF. CONCLUSION MRS is an accurate and precise method for detecting NAFLD in children. PMID:27818597

Elastography in Chronic Liver Disease: Modalities, Techniques, Limitations, and Future Directions

PubMed Central

Srinivasa Babu, Aparna; Wells, Michael L.; Teytelboym, Oleg M.; Mackey, Justin E.; Miller, Frank H.; Yeh, Benjamin M.; Ehman, Richard L.

2016-01-01

Chronic liver disease has multiple causes, many of which are increasing in prevalence. The final common pathway of chronic liver disease is tissue destruction and attempted regeneration, a pathway that triggers fibrosis and eventual cirrhosis. Assessment of fibrosis is important not only for diagnosis but also for management, prognostic evaluation, and follow-up of patients with chronic liver disease. Although liver biopsy has traditionally been considered the reference standard for assessment of liver fibrosis, noninvasive techniques are the emerging focus in this field. Ultrasound-based elastography and magnetic resonance (MR) elastography are gaining popularity as the modalities of choice for quantifying hepatic fibrosis. These techniques have been proven superior to conventional cross-sectional imaging for evaluation of fibrosis, especially in the precirrhotic stages. Moreover, elastography has added utility in the follow-up of previously diagnosed fibrosis, the assessment of treatment response, evaluation for the presence of portal hypertension (spleen elastography), and evaluation of patients with unexplained portal hypertension. In this article, a brief overview is provided of chronic liver disease and the tools used for its diagnosis. Ultrasound-based elastography and MR elastography are explored in depth, including a brief glimpse into the evolution of elastography. Elastography is based on the principle of measuring tissue response to a known mechanical stimulus. Specific elastographic techniques used to exploit this principle include MR elastography and ultrasonography-based static or quasistatic strain imaging, one-dimensional transient elastography, point shear-wave elastography, and supersonic shear-wave elastography. The advantages, limitations, and pitfalls of each modality are emphasized. ©RSNA, 2016 PMID:27689833

Rapid Quantitative Determination of Squalene in Shark Liver Oils by Raman and IR Spectroscopy.

PubMed

Hall, David W; Marshall, Susan N; Gordon, Keith C; Killeen, Daniel P

2016-01-01

Squalene is sourced predominantly from shark liver oils and to a lesser extent from plants such as olives. It is used for the production of surfactants, dyes, sunscreen, and cosmetics. The economic value of shark liver oil is directly related to the squalene content, which in turn is highly variable and species-dependent. Presented here is a validated gas chromatography-mass spectrometry analysis method for the quantitation of squalene in shark liver oils, with an accuracy of 99.0 %, precision of 0.23 % (standard deviation), and linearity of >0.999. The method has been used to measure the squalene concentration of 16 commercial shark liver oils. These reference squalene concentrations were related to infrared (IR) and Raman spectra of the same oils using partial least squares regression. The resultant models were suitable for the rapid quantitation of squalene in shark liver oils, with cross-validation r (2) values of >0.98 and root mean square errors of validation of ≤4.3 % w/w. Independent test set validation of these models found mean absolute deviations of the 4.9 and 1.0 % w/w for the IR and Raman models, respectively. Both techniques were more accurate than results obtained by an industrial refractive index analysis method, which is used for rapid, cheap quantitation of squalene in shark liver oils. In particular, the Raman partial least squares regression was suited to quantitative squalene analysis. The intense and highly characteristic Raman bands of squalene made quantitative analysis possible irrespective of the lipid matrix.

Prevalence of liver fluke infection in Irish horses and assessment of a serological test for diagnosis of equine fasciolosis.

PubMed

Quigley, A; Sekiya, M; Egan, S; Wolfe, A; Negredo, C; Mulcahy, G

2017-03-01

There is little information on the prevalence of Fasciola hepatica infection in the horse population in Ireland or the potential impact of fluke infection on animal health. To investigate F. hepatica infection in the Irish horse population and to assess the diagnostic potential of an indirect enzyme-linked immunosorbent assay (ELISA) based on the F. hepatica recombinant cathepsin L1 (CL1) antigen. Cross-sectional abattoir survey of horses for liver fluke status. Animals (n = 200) were examined at an abattoir between May 2013 and April 2014. Horses were graded ante mortem for body condition score. Blood and faeces were collected and livers were examined post mortem by gross morphology. A cohort (n = 35) of livers were also examined histologically. Haematology and blood biochemistry, including serum liver enzyme activities, were measured and faeces were sedimented for egg counts. Serum was assayed by indirect ELISA using a recombinant CL1. The prevalence of liver fluke infection was 9.5%. There was no correlation between liver fluke status and time of year, breed classification, age group, sex, body condition score, ante mortem assessment, strongyle infection status, serum liver enzyme activities or CL1 concentration. A comparison of the CL1 ELISA in horse sera compared with a reference standard diagnosis showed high specificity of 95.6% (95% confidence interval [CI] 91.5-98.0%), but low sensitivity of 42.1% (95% CI 20.2-66.5%). This study is limited by its nature as an abattoir study, the relatively small number of animals examined (n = 200), and the absence of a known negative group of horses. Blood biomarkers are not good indicators of liver fluke infection and the CL1 ELISA is not a sensitive tool for diagnosis of fluke infection in the horse. The prevalence of F. hepatica in horses indicates that further research is required to assess the potential impact of liver fluke on equine liver health. © 2016 EVJ Ltd.

Evaluation of Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Chronic Liver Diseases.

PubMed

Gani, Rino Alvani; Hasan, Irsan; Sanityoso, Andri; Lesmana, Cosmas Rinaldi A; Kurniawan, Juferdy; Jasirwan, Chyntia Olivia Maurine; Kalista, Kemal Fariz; Lutfie, Lutfie

2017-04-01

acoustic radiation force impulse (ARFI) is a new proposed noninvasive method for liver fibrosis staging. Integrated with B-mode ultrasonography, ARFI can be used to assess liver tissue condition. However its diagnostic accuracy is still being continuously evaluated. Also, there is lack of data regarding the utilization of ARFI in our population. This study aimed to evaluate the diagnostic value of ARFI as an alternative noninvasive modality for fibrosis staging in chronic hepatitis B and hepatitis C patients in our population. we conducted cross-sectional comparison of ARFI imaging and transient elastography on patients who underwent liver biopsy at Cipto Mangunkusumo Hospital. Fibrosis staging using METAVIR scoring system presented as standard reference. A total of 43 patients underwent liver biopsy was evaluated by ARFI imaging and transient elastography. Cut-off values were determined using receiver-operating characteristic (ROC). both liver stiffness determined by ARFI and transient elastography (TE) were moderately correlated with METAVIR score with value of 0.581 and 0.613, respectively (both P<0.01). Diagnostic accuracy of ARFI predicted significant fibrosis (F≥2) with area under receiver operating characteristic curve (AUROC) of 0.773 (95% CI 0.616-0.930) and even better for cirrhosis (F4 fibrosis), expressed as AUROC of 0.856 (95% CI 0.736-0.975). Transient elastography was better for significant fibrosis with AUROC of 0.761 (95% CI 0.601-0.920) and was best for prediction of cirrhosis, expressed as AUROC of 0.845 (95% CI 0.722-0.968). ARFI is provided with more convenient evaluation of liver tissue condition, and its diagnostic accuracy is not significantly different from TE for staging liver fibrosis.

Quantification of hepatic macrosteatosis in living, related liver donors using T1-independent, T2*-corrected chemical shift MRI.

PubMed

Joe, Eugene; Lee, Jeong Min; Kim, Kyung Won; Lee, Kyung Bun; Kim, Soo Jin; Baek, Jee Hyun; Shin, Cheong Il; Suh, Kyung Suk; Yi, Nam Joon; Han, Joon Koo; Choi, Byung Ihn

2012-11-01

To evaluate the diagnostic implications of the iterative decomposition of water and fat using echo-asymmetry and the least-squares estimation (IDEAL) technique to detect hepatic steatosis (HS) in potential liver donors using histopathology as the reference standard. Forty-nine potential liver donors (32 male, 17 female; mean age, 31.7 years) were included. All patients were imaged using the in- and out-of-phase (IOP) gradient-echo (GRE) and IDEAL techniques on a 1.5 T MR scanner. To estimate the hepatic fat fraction (FF), two reviewers performed regions-of-interest measurement in 15 areas of the liver seen on the IOP images and on the IDEAL-FF images. The magnetic resonance imaging (MRI) and pathology values of macrosteatosis were correlated using the Pearson correlation coefficient. We analyzed the diagnostic performance of IOP imaging and IDEAL for detecting HS. The results of the hepatic-FF estimated on IDEAL were well correlated with the histologic degree of macrosteatosis (γ = 0.902, P < 0.001). IDEAL showed 100% sensitivity and 91% specificity for detecting HS, and IOP imaging showed 87.5% sensitivity and 97% specificity, respectively. IDEAL is a useful tool for the preoperative diagnosis of HS in potential living liver donors; it can also help to avoid unnecessary biopsies in these patients. Copyright © 2012 Wiley Periodicals, Inc.

Imaging-based quantification of hepatic fat: methods and clinical applications.

PubMed

Ma, Xiaozhou; Holalkere, Nagaraj-Setty; Kambadakone R, Avinash; Mino-Kenudson, Mari; Hahn, Peter F; Sahani, Dushyant V

2009-01-01

Fatty liver disease comprises a spectrum of conditions (simple hepatic steatosis, steatohepatitis with inflammatory changes, and end-stage liver disease with fibrosis and cirrhosis). Hepatic steatosis is often associated with diabetes and obesity and may be secondary to alcohol and drug use, toxins, viral infections, and metabolic diseases. Detection and quantification of liver fat have many clinical applications, and early recognition is crucial to institute appropriate management and prevent progression. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but results are vulnerable to sampling error. Moreover, it can cause morbidity and complications and cannot be repeated often enough to monitor treatment response. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. Ultrasonography is effective for detecting moderate or severe fatty infiltration but is limited by lack of interobserver reliability and intraobserver reproducibility. Computed tomography allows quantitative and qualitative evaluation and is generally highly accurate and reliable; however, the results may be confounded by hepatic parenchymal changes due to cirrhosis or depositional diseases. Magnetic resonance (MR) imaging with appropriate sequences (eg, chemical shift techniques) has similarly high sensitivity, and MR spectroscopy provides unique advantages for some applications. However, both are expensive and too complex to be used to monitor steatosis. (c) RSNA, 2009.

Temporal and spatial patterns in tumour prevalence in brown bullhead Ameiurus nebulosus (Lesueur) in the tidal Potomac River watershed (USA).

PubMed

Pinkney, A E; Harshbarger, J C; Rutter, M A

2014-10-01

For two decades, fish tumour surveys have been used to monitor habitat quality in the Chesapeake Bay (USA) watershed. Tributaries with sediments contaminated with polynuclear aromatic hydrocarbons (PAHs), known to cause liver neoplasia, were frequently targeted. Here, we compare surveys in brown bullhead Ameiurus nebulosus conducted in 2009-2011 in the tidal Potomac River watershed (including the Anacostia River) with previous surveys. Using logistic regression, we identified length and sex as covariates for liver and skin tumours. We reported a statistically significant decrease in liver tumour probabilities for standardized 280 mm Anacostia bullheads between the 1996 and 2001 samplings (merged collections: female-77.5%, male-43.0%) and 2009-2011 (female-42.2%, male-13.6%). However, liver tumour prevalence in bullheads from the Anacostia, Potomac River (Washington, DC) and Piscataway Creek (17 km downriver) was significantly higher than that for Chesapeake Bay watershed reference locations. The causes of skin tumours in bullheads are uncertain, requiring further research. The similar liver tumour prevalence in these three locations suggests that the problem is regional rather than restricted to the Anacostia. To monitor habitat quality and the success of pollution control actions, we recommend conducting tumour surveys on a 5-year cycle coordinated with sediment chemistry analyses. © 2014 John Wiley & Sons Ltd.

Validation of goose liver fat measurement by QCT and CSE-MRI with biochemical extraction and pathology as reference.

PubMed

Xu, Li; Duanmu, Yangyang; Blake, Glen M; Zhang, Chenxin; Zhang, Yong; Brown, Keenan; Wang, Xiaoqi; Wang, Peng; Zhou, Xingang; Zhang, Manling; Wang, Chao; Guo, Zhe; Guglielmi, Giuseppe; Cheng, Xiaoguang

2018-05-01

This study aimed to validate the accuracy and reliability of quantitative computed tomography (QCT) and chemical shift encoded magnetic resonance imaging (CSE-MRI) to assess hepatic steatosis. Twenty-two geese with a wide range of hepatic steatosis were collected. After QCT and CSE-MRI examinations, the liver of each goose was removed and samples were taken from the left lobe, upper and lower half of the right lobe for biochemical measurement and histology. Fat percentages by QCT and proton density fat fraction by MRI (MRI-PDFF) were measured within the sample regions of biochemical measurement and histology. The accuracy of QCT and MR measurements were assessed through Spearman correlation coefficients (r) and Passing and Bablok regression equations using biochemical measurement as the "gold standard". Both QCT and MRI correlated highly with chemical extraction [r = 0.922 (p < 0.001) and r = 0.949 (p < 0.001) respectively]. Chemically extracted triglyceride was accurately predicted by both QCT liver fat percentages (Y = 0.6 + 0.866 × X) and by MRI-PDFF (Y = -1.8 + 0.773 × X). QCT and CSE-MRI measurements of goose liver fat were accurate and reliable compared with biochemical measurement. • QCT and CSE-MRI can measure liver fat content accurately and reliably • Histological grading of hepatic steatosis has larger sampling variability • QCT and CSE-MRI have potential in the clinical setting.

Feasibility of semiautomated MR volumetry using gadoxetic acid-enhanced MRI at hepatobiliary phase for living liver donors.

PubMed

Lee, Jeongjin; Kim, Kyoung Won; Kim, So Yeon; Kim, Bohyoung; Lee, So Jung; Kim, Hyoung Jung; Lee, Jong Seok; Lee, Moon Gyu; Song, Gi-Won; Hwang, Shin; Lee, Sung-Gyu

2014-09-01

To assess the feasibility of semiautomated MR volumetry using gadoxetic acid-enhanced MRI at the hepatobiliary phase compared with manual CT volumetry. Forty potential live liver donor candidates who underwent MR and CT on the same day, were included in our study. Semiautomated MR volumetry was performed using gadoxetic acid-enhanced MRI at the hepatobiliary phase. We performed the quadratic MR image division for correction of the bias field inhomogeneity. With manual CT volumetry as the reference standard, we calculated the average volume measurement error of the semiautomated MR volumetry. We also calculated the mean of the number and time of the manual editing, edited volume, and total processing time. The average volume measurement errors of the semiautomated MR volumetry were 2.35% ± 1.22%. The average values of the numbers of editing, operation times of manual editing, edited volumes, and total processing time for the semiautomated MR volumetry were 1.9 ± 0.6, 8.1 ± 2.7 s, 12.4 ± 8.8 mL, and 11.7 ± 2.9 s, respectively. Semiautomated liver MR volumetry using hepatobiliary phase gadoxetic acid-enhanced MRI with the quadratic MR image division is a reliable, easy, and fast tool to measure liver volume in potential living liver donors. Copyright © 2013 Wiley Periodicals, Inc.

Genetics Home Reference: cryptogenic cirrhosis

MedlinePlus

... likely result from a condition called non-alcoholic fatty liver disease (NAFLD). In NAFLD, fat accumulates in the ... Information & Resources MedlinePlus (5 links) Encyclopedia: Cirrhosis Encyclopedia: Fatty Liver--Nonalcoholic Encyclopedia: Liver Cancer--Hepatocellular Carcinoma Health Topic: ...

Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS.

PubMed

Schellhaas, Barbara; Görtz, Ruediger S; Pfeifer, Lukas; Kielisch, Christian; Neurath, Markus F; Strobel, Deike

2017-09-01

A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases.For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared.Histology, CE-computed tomography and CE-MRI served as reference standards. The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; p<0.01). Sensitivity, specificity and positive predictive value (PPV) and negative predictive value for ESCULAP/CEUS-LI-RADS were 94.3%/72.4%; 61.5%/69.2%; 94.3%/94%; and 61.5%/27.3%, respectively.The diagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the diagnosis of HCC with CEUS. Washout should not be a necessary prerequisite for the diagnosis of definite HCC. CEUS-LI-RADS in its current version is inferior to ESCULAP for the noninvasive diagnosis of HCC. There are two ways to improve CEUS-LI-RADS: firstly, combination of the categories LR-4 and LR-5 for the diagnosis of definite HCC, and secondly, use of subtotal infiltration of a liver lobe as an additional feature.

Genetics Home Reference: congenital bile acid synthesis defect type 2

MedlinePlus

... Resources (4 links) American Liver Foundation CORE: Fighting Gut and Liver Disease (UK) National Organization for Rare ... reductase, in hepatitis and liver failure in infancy. Gut. 2003 Oct;52(10):1494-9. Citation on ...

FT-IR imaging for quantitative determination of liver fat content in non-alcoholic fatty liver.

PubMed

Kochan, K; Maslak, E; Chlopicki, S; Baranska, M

2015-08-07

In this work we apply FT-IR imaging of large areas of liver tissue cross-section samples (∼5 cm × 5 cm) for quantitative assessment of steatosis in murine model of Non-Alcoholic Fatty Liver (NAFLD). We quantified the area of liver tissue occupied by lipid droplets (LDs) by FT-IR imaging and Oil Red O (ORO) staining for comparison. Two alternative FT-IR based approaches are presented. The first, straightforward method, was based on average spectra from tissues and provided values of the fat content by using a PLS regression model and the reference method. The second one – the chemometric-based method – enabled us to determine the values of the fat content, independently of the reference method by means of k-means cluster (KMC) analysis. In summary, FT-IR images of large size liver sections may prove to be useful for quantifying liver steatosis without the need of tissue staining.

Naturally occurring levels of elements in fishes as determined by PIXE and XRF methods

NASA Astrophysics Data System (ADS)

Tallandini, L.; Giacobini, F.; Turchetto, M.; Galassini, S.; Liu, Q. X.; Shao, H. R.; Moschini, G.; Moro, R.; Gialanella, G.; Ghermandi, G.; Cecchi, R.; Injuk, J.; Valković, V.

1989-04-01

Naturally occurring levels of S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Sb, Sr and Pb were measured in the gills, liver and muscles of fishes ( Zosterisessor ophiocephalus Pall) in the northwestern region of the Adriatic Sea. The overall performance of PIXE and XRF methods was tested by the analysis of standard reference materials. The mean concentration values for elements were calculated from the distribution of experimentally determined concentration values. The obtained data are discussed in the framework of metal metabolism and toxicology.

Task-based optimization of flip angle for fibrosis detection in T1-weighted MRI of liver

PubMed Central

Brand, Jonathan F.; Furenlid, Lars R.; Altbach, Maria I.; Galons, Jean-Philippe; Bhattacharyya, Achyut; Sharma, Puneet; Bhattacharyya, Tulshi; Bilgin, Ali; Martin, Diego R.

2016-01-01

Abstract. Chronic liver disease is a worldwide health problem, and hepatic fibrosis (HF) is one of the hallmarks of the disease. The current reference standard for diagnosing HF is biopsy followed by pathologist examination; however, this is limited by sampling error and carries a risk of complications. Pathology diagnosis of HF is based on textural change in the liver as a lobular collagen network that develops within portal triads. The scale of collagen lobules is characteristically in the order of 1 to 5 mm, which approximates the resolution limit of in vivo gadolinium-enhanced magnetic resonance imaging in the delayed phase. We use MRI of formalin-fixed human ex vivo liver samples as phantoms that mimic the textural contrast of in vivo Gd-MRI. We have developed a local texture analysis that is applied to phantom images, and the results are used to train model observers to detect HF. The performance of the observer is assessed with the area-under-the-receiver–operator-characteristic curve (AUROC) as the figure-of-merit. To optimize the MRI pulse sequence, phantoms were scanned with multiple times at a range of flip angles. The flip angle that was associated with the highest AUROC was chosen as optimal for the task of detecting HF. PMID:27446971

A New Modeling for the Changes in the Distribution of Scatterers in Cirrhotic Liver

NASA Astrophysics Data System (ADS)

Hara, Takashi; Hachiya, Hiroyuki

2000-05-01

The human liver is composed of small hexagonal structures called liver lobules. Cirrhosis destroys these liver lobules and replaces them with permanent connective tissue referred to as regenerative nodules. In this paper, we propose a new modeling technique for changes in the scatterer distribution in liver tissue considering the structure of liver lobules to obtain images of the cirrhotic liver over continuous stages. Using these images, we analyze the relationship between changes in characteristics of biological tissue and changes in B-mode images during progressive liver cirrhosis.

Diagnostic accuracy of contrast-enhanced ultrasound in assessing the therapeutic response to radio frequency ablation for liver tumors: systematic review and meta-analysis.

PubMed

Xuan, Min; Zhou, Fengsheng; Ding, Yan; Zhu, Qiaoying; Dong, Ji; Zhou, Hao; Cheng, Jun; Jiang, Xiao; Wu, Pengxi

2018-04-01

To review the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) used to detect residual or recurrent liver tumors after radiofrequency ablation (RFA). This technique uses contrast-enhanced computer tomography or/and contrast-enhanced magnetic resonance imaging as the gold standard of investigation. MEDLINE, EMBASE, and COCHRANE were systematically searched for all potentially eligible studies comparing CEUS with the reference standard that follows RFA. Risk of bias and applicability concerns were addressed by adopting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled point estimates for sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) with 95% CI were computed before plotting the sROC (summary receiver operating characteristic) curve. Meta-regression and subgroup analysis were used to identify the source of the heterogeneity that was detected. Publication bias was evaluated using Deeks' funnel plot asymmetry test. Ten eligible studies on 1162 lesions that occurred between 2001 and 2016 were included in the final analysis. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable. The pooled sensitivity and specificity of CEUS in detecting residual or recurrent liver tumors had the following values: 0.90 (95% CI 0.85-0.94) and 1.00 (95% CI 0.99-1.00), respectively. Overall DOR was 420.10 (95% CI 142.30-1240.20). The sources of heterogeneity could not be precisely identified by meta-regression or subgroup analysis. No evidence of publication bias was found. This study confirmed that CEUS exhibits high sensitivity and specificity in assessing therapeutic responses to RFA for liver tumors.

Three-dimensional growth dynamics of the liver in the human fetus.

PubMed

Szpinda, Michał; Paruszewska-Achtel, Monika; Woźniak, Alina; Badura, Mateusz; Mila-Kierzenkowska, Celestyna; Wiśniewski, Marcin

2015-07-01

The fetal liver is indubitably the earliest and the most severely affected organ by abnormal fetal growth. The size of the fetal liver assessed by three-dimensional ultrasonography is indispensable in determining the status of fetal growth, nutrition and maturity, and in the early recognition and monitoring fetal micro- and macrosomias. The aim of the present study was to measure the human fetal liver length, transverse and sagittal diameters to establish their age-specific reference intervals, the 3rd, 10th, 50th, 90th, and 97th smoothed centile curves, and the relative growth of the liver calculated for the 50th centile. Using anatomical, digital (NIS-Elements AR 3.0, Nikon) and statistical methods (one-way ANOVA test for paired data and post hoc RIR Tukey test, Shapiro-Wilk test, Fisher's test, Student's t test, the Altman-Chitty method), length, transverse and sagittal diameters of the liver for the 3rd, 10th, 50th, 90th, and 97th centiles were assessed in 69 human fetuses of both sexes (32 males and 37 females) aged 18-30 weeks, derived from spontaneous abortions or stillbirths. No male-female differences (P > 0.05) concerning the three parameters studied were found. During the study period, the fetal liver increased tri-dimensionally: in length from 19.51 ± 1.02 to 39.65 ± 7.05 mm, in transverse diameter from 29.44 ± 3.73 to 53.13 ± 5.31 mm, and in sagittal diameter from 22.97 ± 3.79 to 43.22 ± 5.49 mm. The natural logarithmic models were found to fit the data with gestational age (P < 0.001) in the following five cutoff points: 3rd, 10th, 50th, 90th and 97th centiles. The values of liver parameters in relation to gestational age in weeks were calculated by the following logarithmic regressions: y = -82.778 + 35.752 × ln(age) ± Z × (-2.778 + 0.308 × age) for liver length, y = -123.06 + 52.668 × ln(age) ± Z × (3.156 + 0.049 × age) for liver transverse diameter, and y = -108.94 + 46.052 × ln(age) ± Z × (-0.541 + 0.188 × age) for liver sagittal diameter. For the 50th centile, at the range of 18-30 weeks, the growth rates per week were gradually decreasing from 1.93 to 1.21 mm for length, from 2.85 to 1.79 mm for transverse diameter, and from 2.49 to 1.56 mm for sagittal diameter of the liver (P < 0.05). During the study period both the length-to-transverse diameter ratio and the sagittal-to-transverse diameter ratio of the liver changed little, attaining the values of 0.71 ± 0.11 and 0.87 ± 0.12, respectively. The fetal liver does not reveal sex differences in its length, transverse and sagittal diameters. The fetal liver length, transverse and sagittal diameters grow logarithmically. The regression equations for the estimation of the mean and standard deviation of liver length, transverse and sagittal diameters allow for calculating any desired centiles according to gestational age. The three-dimensional evolution of the fetal liver follows proportionately. The age-specific reference intervals for evolving liver length, transverse and sagittal diameters constitute the normative values of potential relevance in monitoring normal fetal development and screening for disturbances in fetal growth.

Prospective Trial with Optical Molecular Imaging for Percutaneous Interventions in Focal Hepatic Lesions

PubMed Central

Sheth, Rahul A.; Arellano, Ronald S.; Uppot, Raul N.; Samir, Anthony E.; Goyal, Lipika; Zhu, Andrew X.; Gervais, Debra A.

2015-01-01

Purpose To demonstrate the clinical translation of optical molecular imaging (OMI) for the localization of focal hepatic lesions during percutaneous hepatic interventions. Materials and Methods Institutional review board approval was obtained for this prospective, single-center, HIPAA-compliant trial. Patients who were suspected of having hepatocellular carcinoma or liver metastases from colorectal cancer and were scheduled for percutaneous liver biopsy or thermal ablation were eligible for this study. Patients (n = 5) received 0.5 mg per kilogram of body weight of indocyanine green (ICG) intravenously 24 hours prior to their scheduled procedure in this study. Intraprocedurally, a handheld device composed of an endoscope that fits coaxially through a standard 17-gauge introducer needle was advanced into the liver, and real-time measurements of ICG fluorescence were obtained. A point-of-care fluorescence imaging system was used to image ICG fluorescence in biopsy samples. Target-to-background ratios (TBRs) were calculated by dividing the mean fluorescence intensity in the lesion by the mean fluorescence intensity in the adjacent liver parenchyma. The reference standard for determination of proper needle positioning in patients undergoing biopsy was final pathologic analysis of biopsy specimens or follow-up imaging. Results Intraprocedural OMI was successfully performed in six lesions (two lesions in patient 3) in five patients. The median size of the targeted lesions was 16 mm (range, 10–21 mm). Four of five biopsies (80%) yielded an accurate pathologic diagnosis, and one biopsy specimen showed benign liver parenchyma; both ablated lesions showed no residual disease 1 month after the procedure. The median overall added procedure time to perform OMI was 2 minutes. ICG was found to localize with TBRs greater than 2.0 (median, 7.9; range, 2.4–13.4) in all target lesions. No trial-related adverse events were reported. Conclusion The clinical translation of OMI to percutaneous hepatic interventions was demonstrated. © RSNA, 2014 Online supplemental material is available for this article. PMID:25302707

Nonrigid 3D medical image registration and fusion based on deformable models.

PubMed

Liu, Peng; Eberhardt, Benjamin; Wybranski, Christian; Ricke, Jens; Lüdemann, Lutz

2013-01-01

For coregistration of medical images, rigid methods often fail to provide enough freedom, while reliable elastic methods are available clinically for special applications only. The number of degrees of freedom of elastic models must be reduced for use in the clinical setting to archive a reliable result. We propose a novel geometry-based method of nonrigid 3D medical image registration and fusion. The proposed method uses a 3D surface-based deformable model as guidance. In our twofold approach, the deformable mesh from one of the images is first applied to the boundary of the object to be registered. Thereafter, the non-rigid volume deformation vector field needed for registration and fusion inside of the region of interest (ROI) described by the active surface is inferred from the displacement of the surface mesh points. The method was validated using clinical images of a quasirigid organ (kidney) and of an elastic organ (liver). The reduction in standard deviation of the image intensity difference between reference image and model was used as a measure of performance. Landmarks placed at vessel bifurcations in the liver were used as a gold standard for evaluating registration results for the elastic liver. Our registration method was compared with affine registration using mutual information applied to the quasi-rigid kidney. The new method achieved 15.11% better quality with a high confidence level of 99% for rigid registration. However, when applied to the quasi-elastic liver, the method has an averaged landmark dislocation of 4.32 mm. In contrast, affine registration of extracted livers yields a significantly (P = 0.000001) smaller dislocation of 3.26 mm. In conclusion, our validation shows that the novel approach is applicable in cases where internal deformation is not crucial, but it has limitations in cases where internal displacement must also be taken into account.

Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard.

PubMed

Kang, Bo-Kyeong; Yu, Eun Sil; Lee, Seung Soo; Lee, Youngjoo; Kim, Namkug; Sirlin, Claude B; Cho, Eun Yoon; Yeom, Suk Keu; Byun, Jae Ho; Park, Seong Ho; Lee, Moon-Gyu

2012-06-01

The aims of this study were to assess the confounding effects of hepatic iron deposition, inflammation, and fibrosis on hepatic steatosis (HS) evaluation by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to assess the accuracies of MRI and MRS for HS evaluation, using histology as the reference standard. In this institutional review board-approved prospective study, 56 patients gave informed consents and underwent chemical-shift MRI and MRS of the liver on a 1.5-T magnetic resonance scanner. To estimate MRI fat fraction (FF), 4 analysis methods were used (dual-echo, triple-echo, multiecho, and multi-interference), and MRS FF was calculated with T2 correction. Degrees of HS, iron deposition, inflammation, and fibrosis were analyzed in liver resection (n = 37) and biopsy (n = 19) specimens. The confounding effects of histology on fat quantification were assessed by multiple linear regression analysis. Using the histologic degree of HS as the reference standard, the accuracies of each method in estimating HS and diagnosing an HS of 5% or greater were determined by linear regression and receiver operating characteristic analyses. Iron deposition significantly confounded estimations of FF by the dual-echo (P < 0.001) and triple-echo (P = 0.033) methods, whereas no histologic feature confounded the multiecho and multi-interference methods or MRS. The MRS (r = 0.95) showed the strongest correlation with histologic degree of HS, followed by the multiecho (r = 0.92), multi-interference (r = 0.91), triple-echo (r = 0.90), and dual-echo (r = 0.85) methods. For diagnosing HS, the areas under the curve tended to be higher for MRS (0.96) and the multiecho (0.95), multi-interference (0.95), and triple-echo (0.95) methods than for the dual-echo method (0.88) (P ≥ 0.13). The multiecho and multi-interference MRI methods and MRS can accurately quantify hepatic fat, with coexisting histologic abnormalities having no confounding effects.

Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

NASA Astrophysics Data System (ADS)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

2012-02-01

At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia

USGS Publications Warehouse

Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

2009-01-01

Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients with Acute Liver Injury or Failure

PubMed Central

Roberts, Dean W.; Lee, William M.; Hinson, Jack A.; Bai, Shasha; Swearingen, Christopher J.; Stravitz, R. Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M.; Rule, Jody; Fontana, Robert J.; Ganger, Daniel; Reddy, K. Rajender; Liou, Iris; Fix, Oren; James, Laura P.

2017-01-01

Background & Aims A rapid, reliable point-of-care assay to detect acetaminophen protein adducts in serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC, a sensitive and specific quantitative analytical assay) to detect acetaminophen protein adducts. Methods We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using Fisher’s Exact for categorical variables and Kruskal-Wallis Test or Rank-Sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median (and range) AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P<.001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive-predictive value of 89.2%, and a negative-predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen–associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusion The competitive immunoassay AcetaSTAT demonstrates a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. PMID:27641661

Analysis of the efficacy of portal vein embolization for patients with extensive liver malignancy and very low future liver remnant volume, including a comparison with the associating liver partition with portal vein ligation for staged hepatectomy approach.

PubMed

Shindoh, Junichi; Vauthey, Jean-Nicolas; Zimmitti, Giuzeppe; Curley, Steven A; Huang, Steven Y; Mahvash, Armeen; Gupta, Sanjay; Wallace, Michael J; Aloia, Thomas A

2013-07-01

The primary reported indication for the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) technique is in patients with very low future liver remnant volumes. Given the elevated incidence of major morbidity (40%) and liver-related mortality (12%) with ALPPS, we sought to determine the safety and efficacy of percutaneous portal vein embolization (PVE) in a similar patient population. Tumor resectability and morbidity and mortality rates were reviewed for 144 consecutive liver tumor patients with future liver remnant to body weight ratios (LR/BW) less than 0.5%. All patients were referred for preoperative percutaneous right plus segment IV PVE using embolic microspheres, with planned reassessment of the LR/BW 30 days after PVE. Post-PVE outcomes were compared with reported outcomes for ALPPS. Percutaneous PVE was successfully performed in 141 of the 144 study patients (97.9%). Adequate regeneration was observed in 139 patients (98.5%) with median post-PVE LR/BW rising from 0.33% to 0.52% (p < 0.0001), representing a per-patient median regeneration rate of 62% (range 0.3% to 379%). In total, 104 patients underwent extended right hepatectomy (n = 102) or right hepatectomy (n = 2). The remaining 40 patients (27.8%) were not resectable due to short-interval disease progression (27 patients, 18.5%), insufficient liver regeneration (5 patients, 3.5%), and medical comorbidities (8 patients, 5.6%). After resection, the following outcomes were observed: major morbidity: 33.0% (34 of 104), liver insufficiency: 12.5% (13 of 104), and 90-day liver-related mortality: 5.8% (6 of 104). These oncologic and technical results compare favorably with those of ALPPS. Based on its ability to select oncologically resectable patients and superior safety and efficacy profiles, percutaneous right + segment IV PVE and interval surgery remains the standard of care for patients with very low future liver remnant volumes. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Computer-assisted liver graft steatosis assessment via learning-based texture analysis.

PubMed

Moccia, Sara; Mattos, Leonardo S; Patrini, Ilaria; Ruperti, Michela; Poté, Nicolas; Dondero, Federica; Cauchy, François; Sepulveda, Ailton; Soubrane, Olivier; De Momi, Elena; Diaspro, Alberto; Cesaretti, Manuela

2018-05-23

Fast and accurate graft hepatic steatosis (HS) assessment is of primary importance for lowering liver dysfunction risks after transplantation. Histopathological analysis of biopsied liver is the gold standard for assessing HS, despite being invasive and time consuming. Due to the short time availability between liver procurement and transplantation, surgeons perform HS assessment through clinical evaluation (medical history, blood tests) and liver texture visual analysis. Despite visual analysis being recognized as challenging in the clinical literature, few efforts have been invested to develop computer-assisted solutions for HS assessment. The objective of this paper is to investigate the automatic analysis of liver texture with machine learning algorithms to automate the HS assessment process and offer support for the surgeon decision process. Forty RGB images of forty different donors were analyzed. The images were captured with an RGB smartphone camera in the operating room (OR). Twenty images refer to livers that were accepted and 20 to discarded livers. Fifteen randomly selected liver patches were extracted from each image. Patch size was [Formula: see text]. This way, a balanced dataset of 600 patches was obtained. Intensity-based features (INT), histogram of local binary pattern ([Formula: see text]), and gray-level co-occurrence matrix ([Formula: see text]) were investigated. Blood-sample features (Blo) were included in the analysis, too. Supervised and semisupervised learning approaches were investigated for feature classification. The leave-one-patient-out cross-validation was performed to estimate the classification performance. With the best-performing feature set ([Formula: see text]) and semisupervised learning, the achieved classification sensitivity, specificity, and accuracy were 95, 81, and 88%, respectively. This research represents the first attempt to use machine learning and automatic texture analysis of RGB images from ubiquitous smartphone cameras for the task of graft HS assessment. The results suggest that is a promising strategy to develop a fully automatic solution to assist surgeons in HS assessment inside the OR.

Reproducibility of MRI-Determined Proton Density Fat Fraction Across Two Different MR Scanner Platforms

PubMed Central

Kang, Geraldine H.; Cruite, Irene; Shiehmorteza, Masoud; Wolfson, Tanya; Gamst, Anthony C.; Hamilton, Gavin; Bydder, Mark; Middleton, Michael S.; Sirlin, Claude B.

2016-01-01

Purpose To evaluate magnetic resonance imaging (MRI)-determined proton density fat fraction (PDFF) reproducibility across two MR scanner platforms and, using MR spectroscopy (MRS)-determined PDFF as reference standard, to confirm MRI-determined PDFF estimation accuracy. Materials and Methods This prospective, cross-sectional, crossover, observational pilot study was approved by an Institutional Review Board. Twenty-one subjects gave written informed consent and underwent liver MRI and MRS at both 1.5T (Siemens Symphony scanner) and 3T (GE Signa Excite HD scanner). MRI-determined PDFF was estimated using an axial 2D spoiled gradient-recalled echo sequence with low flip-angle to minimize T1 bias and six echo-times to permit correction of T2* and fat-water signal interference effects. MRS-determined PDFF was estimated using a stimulated-echo acquisition mode sequence with long repetition time to minimize T1 bias and five echo times to permit T2 correction. Interscanner reproducibility of MRI determined PDFF was assessed by correlation analysis; accuracy was assessed separately at each field strength by linear regression analysis using MRS-determined PDFF as reference standard. Results 1.5T and 3T MRI-determined PDFF estimates were highly correlated (r = 0.992). MRI-determined PDFF estimates were accurate at both 1.5T (regression slope/intercept = 0.958/−0.48) and 3T (slope/intercept = 1.020/0.925) against the MRS-determined PDFF reference. Conclusion MRI-determined PDFF estimation is reproducible and, using MRS-determined PDFF as reference standard, accurate across two MR scanner platforms at 1.5T and 3T. PMID:21769986

Reproducibility of MRI-determined proton density fat fraction across two different MR scanner platforms.

PubMed

Kang, Geraldine H; Cruite, Irene; Shiehmorteza, Masoud; Wolfson, Tanya; Gamst, Anthony C; Hamilton, Gavin; Bydder, Mark; Middleton, Michael S; Sirlin, Claude B

2011-10-01

To evaluate magnetic resonance imaging (MRI)-determined proton density fat fraction (PDFF) reproducibility across two MR scanner platforms and, using MR spectroscopy (MRS)-determined PDFF as reference standard, to confirm MRI-determined PDFF estimation accuracy. This prospective, cross-sectional, crossover, observational pilot study was approved by an Institutional Review Board. Twenty-one subjects gave written informed consent and underwent liver MRI and MRS at both 1.5T (Siemens Symphony scanner) and 3T (GE Signa Excite HD scanner). MRI-determined PDFF was estimated using an axial 2D spoiled gradient-recalled echo sequence with low flip-angle to minimize T1 bias and six echo-times to permit correction of T2* and fat-water signal interference effects. MRS-determined PDFF was estimated using a stimulated-echo acquisition mode sequence with long repetition time to minimize T1 bias and five echo times to permit T2 correction. Interscanner reproducibility of MRI determined PDFF was assessed by correlation analysis; accuracy was assessed separately at each field strength by linear regression analysis using MRS-determined PDFF as reference standard. 1.5T and 3T MRI-determined PDFF estimates were highly correlated (r = 0.992). MRI-determined PDFF estimates were accurate at both 1.5T (regression slope/intercept = 0.958/-0.48) and 3T (slope/intercept = 1.020/0.925) against the MRS-determined PDFF reference. MRI-determined PDFF estimation is reproducible and, using MRS-determined PDFF as reference standard, accurate across two MR scanner platforms at 1.5T and 3T. Copyright © 2011 Wiley-Liss, Inc.

Anatomical parameterization for volumetric meshing of the liver

NASA Astrophysics Data System (ADS)

Vera, Sergio; González Ballester, Miguel A.; Gil, Debora

2014-03-01

A coordinate system describing the interior of organs is a powerful tool for a systematic localization of injured tissue. If the same coordinate values are assigned to specific anatomical landmarks, the coordinate system allows integration of data across different medical image modalities. Harmonic mappings have been used to produce parametric coordinate systems over the surface of anatomical shapes, given their flexibility to set values at specific locations through boundary conditions. However, most of the existing implementations in medical imaging restrict to either anatomical surfaces, or the depth coordinate with boundary conditions is given at sites of limited geometric diversity. In this paper we present a method for anatomical volumetric parameterization that extends current harmonic parameterizations to the interior anatomy using information provided by the volume medial surface. We have applied the methodology to define a common reference system for the liver shape and functional anatomy. This reference system sets a solid base for creating anatomical models of the patient's liver, and allows comparing livers from several patients in a common framework of reference.

Nonalcoholic Fatty Liver Disease: Diagnostic and Fat-Grading Accuracy of Low-Flip-Angle Multiecho Gradient-Recalled-Echo MR Imaging at 1.5 T

PubMed Central

Yokoo, Takeshi; Bydder, Mark; Hamilton, Gavin; Middleton, Michael S.; Gamst, Anthony C.; Wolfson, Tanya; Hassanein, Tarek; Patton, Heather M.; Lavine, Joel E.; Schwimmer, Jeffrey B.; Sirlin, Claude B.

2009-01-01

Purpose: To assess the accuracy of four fat quantification methods at low-flip-angle multiecho gradient-recalled-echo (GRE) magnetic resonance (MR) imaging in nonalcoholic fatty liver disease (NAFLD) by using MR spectroscopy as the reference standard. Materials and Methods: In this institutional review board–approved, HIPAA-compliant prospective study, 110 subjects (29 with biopsy-confirmed NAFLD, 50 overweight and at risk for NAFLD, and 31 healthy volunteers) (mean age, 32.6 years ± 15.6 [standard deviation]; range, 8–66 years) gave informed consent and underwent MR spectroscopy and GRE MR imaging of the liver. Spectroscopy involved a long repetition time (to suppress T1 effects) and multiple echo times (to estimate T2 effects); the reference fat fraction (FF) was calculated from T2-corrected fat and water spectral peak areas. Imaging involved a low flip angle (to suppress T1 effects) and multiple echo times (to estimate T2* effects); imaging FF was calculated by using four analysis methods of progressive complexity: dual echo, triple echo, multiecho, and multiinterference. All methods except dual echo corrected for T2* effects. The multiinterference method corrected for multiple spectral interference effects of fat. For each method, the accuracy for diagnosis of fatty liver, as defined with a spectroscopic threshold, was assessed by estimating sensitivity and specificity; fat-grading accuracy was assessed by comparing imaging and spectroscopic FF values by using linear regression. Results: Dual-echo, triple-echo, multiecho, and multiinterference methods had a sensitivity of 0.817, 0.967, 0.950, and 0.983 and a specificity of 1.000, 0.880, 1.000, and 0.880, respectively. On the basis of regression slope and intercept, the multiinterference (slope, 0.98; intercept, 0.91%) method had high fat-grading accuracy without statistically significant error (P > .05). Dual-echo (slope, 0.98; intercept, −2.90%), triple-echo (slope, 0.94; intercept, 1.42%), and multiecho (slope, 0.85; intercept, −0.15%) methods had statistically significant error (P < .05). Conclusion: Relaxation- and interference-corrected fat quantification at low-flip-angle multiecho GRE MR imaging provides high diagnostic and fat-grading accuracy in NAFLD. © RSNA, 2009 PMID:19221054

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

PubMed Central

Lee, Sangheun; Kim, Do Young

2014-01-01

Chronic hepatitis B (CHB) infection is a major public health problem associated with significant morbidity and mortality worldwide. Twenty-three percent of patients with CHB progress naturally to liver cirrhosis, which was earlier thought to be irreversible. However, it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs. Thus, early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB. Liver biopsy is the reference standard for assessment of liver fibrosis. However, the method is invasive, and is associated with pain and complications that can be fatal. In addition, intra- and inter-observer variability compromises the accuracy of liver biopsy data. Only small tissue samples are obtained and fibrosis is heterogeneous in such samples. This confounds the two types of observer variability mentioned above. Such limitations have encouraged development of non-invasive methods for assessment of fibrosis. These include measurements of serum biomarkers of fibrosis; and assessment of liver stiffness via transient elastography, acoustic radiation force impulse imaging, real-time elastography, or magnetic resonance elastography. Although significant advances have been made, most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection. In the present review, we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice. PMID:24574713

Fat content, fatty acid pattern and iron content in livers of turkeys with hepatic lipidosis.

PubMed

Visscher, Christian; Middendorf, Lea; Günther, Ronald; Engels, Alexandra; Leibfacher, Christof; Möhle, Henrik; Düngelhoef, Kristian; Weier, Stefan; Haider, Wolfram; Radko, Dimitri

2017-05-30

The so-called "hepatic lipidosis" in turkeys is an acute progressive disease associated with a high mortality rate in a very short time. Dead animals show a massive fatty degeneration of the liver. The cause is still unclear. Previous findings suggest that there may be parallels to human non-alcoholic fatty liver disease. The object of the study was to examine the changes in the fat contents, the fatty acid composition and the iron content in livers of animals, which have died from hepatic lipidosis. The conspicuous livers (n = 85) were collected from 20 flocks where the phenomenon of massive increased animal losses accompanied by marked macroscopically visible pathological liver steatosis suddenly occurred. For comparison and as a reference, livers (n = 16) of two healthy flocks were taken. Healthy and diseased flocks were fed identical diets concerning official nutrient recommendations and were operating under standardized, comparable conventional conditions. Compared to livers of healthy animals, in the livers of turkeys died from hepatic lipidosis there were found massively increased fat levels (130 ± 33.2 vs. 324 ± 101 g/kg dry matter-DM). In all fatty livers, different fatty acids concentrations were present in significantly increased concentrations compared to controls (palmitic acid: 104 g/kg DM, +345%; palmitoleic acid: 18.0 g/kg DM, + 570%; oleic acid: 115 g/kg DM, +437%). Fatty acids concentrations relevant for liver metabolism and inflammation were significantly reduced (arachidonic acid: 2.92 g/kg DM, -66.6%; eicosapentaenoic acid: 0.141 g/kg DM, -78.3%; docosahexaenoic acid: 0.227 g/kg DM, -90.4%). The ratio of certain fatty acids to one another between control and case livers changed analogously to liver diseases in humans (e.g.: C18:0/C16:0 - 0.913 against 0.311; C16:1n7/C16:0 - 0.090 against 0.165; C18:1/C18:0 - 0.938 against 4.03). The iron content in the liver tissue also increased massively (271 ± 51.5 vs 712 ± 214 mg/kg DM). The hepatic lipidosis has a massive impact on the lipid content, the lipid composition and the iron content in the liver. The character of the metabolic disorder includes parallels to the non-alcoholic steatohepatitis in humans.

Acute liver damage and ecstasy ingestion.

PubMed Central

Ellis, A J; Wendon, J A; Portmann, B; Williams, R

1996-01-01

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3 PMID:8675102

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

PubMed Central

Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schwarzenboeck, Alexander; Schulze, Johannes; Eickhoff, Axel

2014-01-01

Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved. PMID:24653791

Standardized surgical techniques for adult living donor liver transplantation using a modified right lobe graft: a video presentation from bench to reperfusion.

PubMed

Hwang, Shin; Ha, Tae-Yong; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

2016-08-01

After having experienced more than 2,000 cases of adult living donor liver transplantation (LDLT), we established the concepts of right liver graft standardization. Right liver graft standardization intends to provide hemodynamics-based and regeneration-compliant reconstruction of vascular inflow and outflow. Right liver graft standardization consists of the following components: Right hepatic vein reconstruction includes a combination of caudal-side deep incision and patch venoplasty of the graft right hepatic vein to remove the acute angle between the graft right hepatic vein and the inferior vena cava; middle hepatic vein reconstruction includes interposition of a uniform-shaped conduit with large-sized homologous or prosthetic grafts; if the inferior right hepatic vein is present, its reconstruction includes funneling and unification venoplasty for multiple short hepatic veins; if donor portal vein anomaly is present, its reconstruction includes conjoined unification venoplasty for two or more portal vein orifices. This video clip that shows the surgical technique from bench to reperfusion was a case presentation of adult LDLT using a modified right liver graft from the patient's son. Our intention behind proposing the concept of right liver graft standardization is that it can be universally applicable and may guarantee nearly the same outcomes regardless of the surgeon's experience. We believe that this reconstruction model would be primarily applied to a majority of adult LDLT cases.

Screening esophagus during routine ultrasound: medical and cost benefits.

PubMed

Abd Elrazek, Abd Elrazek M A; Eid, Khaled A; El-Sherif, Abd Elhalim A; Abd El Al, Usama M; El-Sherbiny, Samir M; Bilasy, Shymaa E

2015-01-01

Cost-effectiveness analysis is an approach used to determine the value of a medical care option and refers to a method used to assess the costs and health benefits of an intervention. Upon the diagnosis of liver cirrhosis, the current guidelines recommend that all cirrhotic patients have to be screened for the presence of esophageal varices by endoscopy. In addition, patients with a positive family history of esophageal cancer are screened annually. These approaches place a heavy burden on endoscopy units, and repeated testing over time may have a detrimental effect on patient compliance. Following the recommendations of a recent study entitled 'Detection of risky esophageal varices using two dimensional ultrasound: when to perform endoscopy', the intra-abdominal portion of the esophagus of 1100 patients was divided into a hepatic group, which included 650 patients, and a nonhepatic group, which included 450 patients, who presented with manifestations of liver diseases and gastrointestinal symptoms, respectively, and were examined using standard two-dimensional ultrasound (US) to evaluate cost effectiveness, standard issues, and medical benefits using conventional US. The overall effectiveness analysis of 1100 patients yielded a 41% cost standard benefit calculated to be $114,760 in a 6-month study. Two-dimensional US can play an important role in screening for esophageal abnormalities, thus saving money and time. The esophagus should be screened during routine conventional abdominal US.

Single-breath-hold abdominal [Formula: see text]  mapping using 3D Cartesian Look-Locker with spatiotemporal sparsity constraints.

PubMed

Lugauer, Felix; Wetzl, Jens; Forman, Christoph; Schneider, Manuel; Kiefer, Berthold; Hornegger, Joachim; Nickel, Dominik; Maier, Andreas

2018-06-01

Our aim was to develop and validate a 3D Cartesian Look-Locker [Formula: see text] mapping technique that achieves high accuracy and whole-liver coverage within a single breath-hold. The proposed method combines sparse Cartesian sampling based on a spatiotemporally incoherent Poisson pattern and k-space segmentation, dedicated for high-temporal-resolution imaging. This combination allows capturing tissue with short relaxation times with volumetric coverage. A joint reconstruction of the 3D + inversion time (TI) data via compressed sensing exploits the spatiotemporal sparsity and ensures consistent quality for the subsequent multistep [Formula: see text] mapping. Data from the National Institute of Standards and Technology (NIST) phantom and 11 volunteers, along with reference 2D Look-Locker acquisitions, are used for validation. 2D and 3D methods are compared based on [Formula: see text] values in different abdominal tissues at 1.5 and 3 T. [Formula: see text] maps obtained from the proposed 3D method compare favorably with those from the 2D reference and additionally allow for reformatting or volumetric analysis. Excellent agreement is shown in phantom [bias[Formula: see text] < 2%, bias[Formula: see text] < 5% for (120; 2000) ms] and volunteer data (3D and 2D deviation < 4% for liver, muscle, and spleen) for clinically acceptable scan (20 s) and reconstruction times (< 4 min). Whole-liver [Formula: see text] mapping with high accuracy and precision is feasible in one breath-hold using spatiotemporally incoherent, sparse 3D Cartesian sampling.

PCBs, liver lesions, and biomarker responses in adult walleye (Stizostedium vitreum vitreum) collected from Green Bay, Wisconsin

USGS Publications Warehouse

Barron, Mace G.; Anderson, Michael J.; Cacela, Dave; Lipton, Joshua; Teh, Swee J.; Hinton, David E.; Zelikoff, Judith T.; Dikkeboom, Audrey L.; Tillitt, Donald E.; Holey, Mark; Denslow, Nancy

2000-01-01

Adult walleye were collected from several locations in the Lower Fox River and Green Bay, Wisconsin (the assessment area) and two relatively uncontaminated reference locations (Lake Winnebago and Patten Lake, Wisconsin) between July and October in 1996 and 1997. Whole body and liver samples collected in 1996 were analyzed for total PCBs, PCB congeners, and liver histological lesions. Follow-up sampling in 1997 included examination of liver histopathology, PCBs in liver samples, measurement of ethoxyresorufin-O-deethylase (EROD) activity, immunological evaluation of kidney and blood samples, measurement of plasma vitellogenin, and examination of tissues for parasites as well as bacterial and viral infections. Mean PCB concentrations in whole body and liver samples were elevated in assessment area walleye (4.6 to 8.6 and 3.6 to 6.4 mg/kg wet weight, respectively) compared to PCB concentrations in reference areas (0.04 mg/kg in walleye fillets from Lake Winnebago). A significant (p < 0.01) elevation was observed in the prevalence (26%) of hepatic preneoplastic foci of cellular alteration (FCA) and neoplasms in 5 to 8 year old walleye collected from the assessment area, compared to reference area fish (6% prevalence). Walleye from the assessment area also contained multiple FCA and hepatic tumors per liver sample, whereas no tumors and a reduced prevalence of FCA were observed in reference area walleye. Both tumors and FCA were more prevalent in female fish than in male fish within the 5 to 8 year age classes. There were no remarkable effects on immunological parameters in assessment area walleye, although hematocrit was elevated and blood monocyte counts were 40% lower than those of reference area fish. The data did not show any clear distinctions in the prevalence of disease between reference and assessment area walleye. EROD activity was similar in assessment area and reference area walleye. Plasma vitellogenin was elevated in female walleye from eastern Green Bay, but was not detected in male fish from this location. The results of this investigation demonstrate significant elevation in hepatic preneoplastic lesions and hepatocellular adenomas and carcinomas in assessment area walleye exposed to elevated concentrations of PCBs. These histopathological lesions are consistent with long-term exposure to tumor promoters such as PCBs, although quantitative association between tumors and PCBs was not observed at the level of the individual fish. Additional research would be needed to elucidate the causal mechanisms underlying tumorigenesis.

Micro-quantity tissue digestion for metal measurements by use of a microwave acid-digestion bomb.

PubMed

Nicholson, J R; Savory, M G; Savory, J; Wills, M R

1989-03-01

We describe a simple and convenient method for processing small amounts of tissue samples for trace-metal measurements by atomic absorption spectrometry, by use of a modified Parr microwave digestion bomb. Digestion proceeds rapidly (less than or equal to 90 s) in a sealed Teflon-lined vessel that eliminates contamination or loss from volatilization. Small quantities of tissue (5-100 mg dry weight) are digested in high-purity nitric acid, yielding concentrations of analyte that can be measured directly without further sample manipulation. We analyzed National Institute of Standards and Technology bovine liver Standard Reference Material to verify the accuracy of the technique. We assessed the applicability of the technique to analysis for aluminum in bone by comparison with a dry ashing procedure.

[Clinical efficacy of cycloferon in complex therapy of infectious mononucleosis in pediatrics].

PubMed

Kasymova, E B; Bashkina, O A; Galimzianov, Kh M

2011-01-01

The results of the cycloferon use in therapy of 80 children at the age of 1 to 15 years with infectious mononucleosis are presented. The children were divided by chance sampling into two comparable groups of 40 subjects each. In the first group the children in addition to the standard therapy were treated with cycloferon for 10 days, intramuscularly or orally depending on the age. The reference group included the patients under the standard therapy alone. The efficacy of the drug was evaluated by reduction and more rapid disappearance of the main clinical symptoms of the disease. The improvement of certain laboratory indices, including those of the liver protein synthesis function were recorded, that allowed to reduce the hospitalization term. No side effects of the cycloferon use were observed.

Anemia and iron deficiency in gastrointestinal and liver conditions

PubMed Central

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-01-01

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice. PMID:27672287

Anemia and iron deficiency in gastrointestinal and liver conditions.

PubMed

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-09-21

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

The impact of conversion from prograf to generic tacrolimus in liver and kidney transplant recipients with stable graft function.

PubMed

Momper, J D; Ridenour, T A; Schonder, K S; Shapiro, R; Humar, A; Venkataramanan, R

2011-09-01

Bioequivalence of the recently available generic tacrolimus formulation, manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma, Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in transplant patients have not been evaluated. Tacrolimus trough concentrations and indices of liver and kidney function were recorded before and after generic substitution in 48 liver and 55 kidney transplant recipients. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (± SD) was 184.1 (± 123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (± 87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D-ratios in kidney transplant patients were 125.3 (± 92.7) and 110.4 (± 79.2) ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p < 0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver and 0.87 ng/mL in kidney transplant patients following the switch, after accounting for all significant covariates. No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution. These results suggest that transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz-generic product provided trough concentrations are closely monitored following the substitution. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Determination of glycated hemoglobin in patients with advanced liver disease

PubMed Central

Lahousen, Theresa; Hegenbarth, Karin; Ille, Rottraut; Lipp, Rainer W.; Krause, Robert; Little, Randie R.; Schnedl, Wolfgang J.

2004-01-01

AIM: To evaluate the glycated hemoglobin (HbA 1c) determination methods and to determine fructosamine in patients with chronic hepatitis, compensated cirrhosis and in patients with chronic hepatitis treated with ribavirin. METHODS: HbA1c values were determined in 15 patients with compensated liver cirrhosis and in 20 patients with chronic hepatitis using the ion-exchange high performance liquid chromatography and the immunoassay methods. Fructosamine was determined using nitroblue tetrazolium. RESULTS: Forty percent of patients with liver cirrhosis had HbA1c results below the non-diabetic reference range by at least one HbA1c method, while fructosamine results were either within the reference range or elevated. Twenty percent of patients with chronic hepatitis (hepatic fibrosis) had HbA1c results below the non -diabetic reference range by at least one HbA1c method. In patients with chronic hepatitis treated with ribavirin, 50% of HbA1c results were below the non-diabetic reference using at least one of the HbA1c methods. CONCLUSION: Only evaluated in context with all liver function parameters as well as a red blood count including reticulocytes, HbA 1c results should be used in patients with advanced liver disease. HbA 1c and fructosamine measurements should be used with caution when evaluating long-term glucose control in patients with hepatic cirrhosis or in patients with chronic hepatitis and ribavirin treatment. PMID:15259084

Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat Using a New Quantitative Ultrasound Technique.

PubMed

Lin, Steven C; Heba, Elhamy; Wolfson, Tanya; Ang, Brandon; Gamst, Anthony; Han, Aiguo; Erdman, John W; O'Brien, William D; Andre, Michael P; Sirlin, Claude B; Loomba, Rohit

2015-07-01

Liver biopsy analysis is the standard method used to diagnose nonalcoholic fatty liver disease (NAFLD). Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis, but is expensive. Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity, specificity, and quantitative accuracy, and results vary among technicians. A new quantitative ultrasound (QUS) technique can identify steatosis in animal models. We assessed the accuracy of QUS in the diagnosis and quantification of hepatic steatosis, comparing findings with those from magnetic resonance imaging proton density fat fraction (MRI-PDFF) analysis as a reference. We performed a prospective, cross-sectional analysis of a cohort of adults (N = 204) with NAFLD (MRI-PDFF, ≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California, San Diego, from February 2012 through March 2014. QUS parameters and backscatter coefficient (BSC) values were calculated. Patients were assigned randomly to training (n = 102; mean age, 51 ± 17 y; mean body mass index, 31 ± 7 kg/m(2)) and validation (n = 102; mean age, 49 ± 17 y; body mass index, 30 ± 6 kg/m(2)) groups; 69% of patients in each group had NAFLD. BSC (range, 0.00005-0.25 1/cm-sr) correlated with MRI-PDFF (Spearman ρ = 0.80; P < .0001). In the training group, the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 (95% confidence interval, 0.95-1.00; P < .0001). The optimal BSC cut-off value identified patients with NAFLD in the training and validation groups with 93% and 87% sensitivity, 97% and 91% specificity, 86% and 76% negative predictive values, and 99% and 95% positive predictive values, respectively. QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis, based on a cross-sectional analysis that used MRI-PDFF as the reference. With further validation, QUS could be an inexpensive, widely available method to screen the general or at-risk population for NAFLD. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Utility of the ELF Test for Detecting Steatohepatitis in Morbid Obese Patients with Suspicion of Nonalcoholic Fatty Liver Disease.

PubMed

López, Iria Cebreiros; Aroca, Florentina Guzmán; Bernal, Maria Dolores Frutos; Mompeán, Juan Antonio Luján; Bernal, Águeda Bas; Martínez, Antonio Miguel Hernández; Barba, Enrique Martínez; Velasco, Jose Antonio Noguera; Paricio, Pascual Parilla

2017-09-01

Morbid obese patients have a high rate of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NASH is related to the progression and poor evolution of chronic hepatopathy in NAFLD, so that its detection makes it possible to identify the subjects who are most at risk in order to prioritize treatment. The ELF test (Enhanced Liver Fibrosis test; Siemens Diagnostics, NY, USA) has been assessed for its capacity to detect fibrosis in patients with NAFLD, but its capacity for diagnosing NASH has not been checked. Our objective is to determine the utility of the ELF test for detecting NASH in morbid obese patients with suspected NAFLD. ELF values were determined in a cohort of obese patients who underwent bariatric surgery with suspected NAFLD. Liver biopsy was used as the reference standard. The values of ELF were significantly higher in patients with NASH (p = 0.002) and in those who presented with metabolic syndrome (p = 0.047). An ELF cut-off point of 8.72 allows the detection of patients with NASH with a sensitivity of 71.4% and a specificity of 74.1% (AUC = 0.742, p = 0.002). The ELF test is efficient for the identification of obese patients with NAFLD and early signs of steatohepatitis and fibrosis.

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PubMed

Bonekamp, David; Bonekamp, Susanne; Ou, Hsin-You; Torbenson, Michael S; Corona-Villalobos, Celia Pamela; Mezey, Esteban; Kamel, Ihab R

2014-11-01

Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC. © 2013 Wiley Periodicals, Inc.

Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease.

PubMed

van de Peppel, Ivo P; Bertolini, Anna; Jonker, Johan W; Bodewes, Frank A J A; Verkade, Henkjan J

2017-11-01

To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD). The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is lacking. Over the past years, new techniques to diagnose features of CFLD, such as transient elastography, have been investigated. Although most of these tests confirm cystic fibrosis-related liver involvement (CFLI), they are, however, not suitable to distinguish various phenotypical presentations or predict progression to clinically relevant cirrhosis or portal hypertension. A combined initiative from the European and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has been started, aimed to obtain consensus on CFLD criteria and definitions. Currently, only ursodeoxycholic acid is used in CFLD treatment, although it has not been convincingly demonstrated to change the natural course of the disease. Drugs that directly target cystic fibrosis transmembrane conductance regulator protein dysfunction show promising results; however, more long-term follow-up and validation studies are needed. CFLD is an umbrella term referring to a wide variety of liver manifestations with variable clinical needs and consequences. CFLD with portal hypertension is the most severe form of CFLD due to its significant implications on morbidity and mortality. The clinical relevance of other CFLI is uncertain. Consensus on CFLD definitions is essential to validate new diagnostic tools and therapeutic outcome measures.

Functional integrity of the interrenal tissue of yellow perch from contaminated sites tested in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Girard, C.; Brodeur, J.C.; Hontela, A.

1995-12-31

The normal activation of the hypothalamo-pituitary-interrenal axis (HPI axis) in response to capture is disrupted in fish subjected to life-long exposure to heavy metals, PCBs and PAHs. The ability to increase plasma cortisol in yellow perch (Perca flavescens) from sites contaminated by heavy metals and organic compounds, and from a reference site was assessed by the Capture stress test and by the ACTH Challenge test, a new standardized in vivo method designed for field studies. The effects of seasonal factors, such as temperature and gonadal maturity on these tests were investigated. Measures of liver and muscle glycogen and histopathology weremore » made to further characterize the biochemical and structural changes that may occur along with hormonal changes. The Capture stress test showed that an acute source of stress induced a lower cortisol response in fish from the highly contaminated site compared to the reference site, revealing a functional impairment of the HPI axis. The ACTH Challenge test showed that the hormonal responsiveness of the cortisol-secreting interrenal tissue, stimulated by a standard dose of ACTH injected i.p., was lower in fish from the highly contaminated site than the reference site. Spring is the season during which the impairment was the most evident. The possibility of using the reduced capacity of feral fish to respond to a standardized ACTH Challenge as an early bioindicator of toxic stress is discussed.« less

Accuracy of Liver Fat Quantification With Advanced CT, MRI, and Ultrasound Techniques: Prospective Comparison With MR Spectroscopy.

PubMed

Kramer, Harald; Pickhardt, Perry J; Kliewer, Mark A; Hernando, Diego; Chen, Guang-Hong; Zagzebski, James A; Reeder, Scott B

2017-01-01

The purpose of this study was to prospectively evaluate the accuracy of proton-density fat-fraction, single- and dual-energy CT (SECT and DECT), gray-scale ultrasound (US), and US shear-wave elastography (US-SWE) in the quantification of hepatic steatosis with MR spectroscopy (MRS) as the reference standard. Fifty adults who did not have symptoms (23 men, 27 women; mean age, 57 ± 5 years; body mass index, 27 ± 5) underwent liver imaging with un-enhanced SECT, DECT, gray-scale US, US-SWE, proton-density fat-fraction MRI, and MRS for this prospective trial. MRS voxels for the reference standard were colocalized with all other modalities under investigation. For SECT (120 kVp), attenuation values were recorded. For rapid-switching DECT (80/140 kVp), monochromatic images (70-140 keV) and fat density-derived material decomposition images were reconstructed. For proton-density fat fraction MRI, a quantitative chemical shift-encoded method was used. For US, echogenicity was evaluated on a qualitative 0-3 scale. Quantitative US shear-wave velocities were also recorded. Data were analyzed by linear regression for each technique compared with MRS. There was excellent correlation between MRS and both proton-density fat-fraction MRI (r 2 = 0.992; slope, 0.974; intercept, -0.943) and SECT (r 2 = 0.856; slope, -0.559; intercept, 35.418). DECT fat attenuation had moderate correlation with MRS measurements (r 2 = 0.423; slope, 0.034; intercept, 8.459). There was good correlation between qualitative US echogenicity and MRS measurements with a weighted kappa value of 0.82. US-SWE velocity did not have reliable correlation with MRS measurements (r 2 = 0.004; slope, 0.069; intercept, 6.168). Quantitative MRI proton-density fat fraction and SECT fat attenuation have excellent linear correlation with MRS measurements and can serve as accurate noninvasive biomarkers for quantifying steatosis. Material decomposition with DECT does not improve the accuracy of fat quantification over conventional SECT attenuation. US-SWE has poor accuracy for liver fat quantification.

Age-specific absolute and relative organ weight distributions for B6C3F1 mice.

PubMed

Marino, Dale J

2012-01-01

The B6C3F1 mouse is the standard mouse strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). While numerous reports have been published on growth, survival, and tumor incidence, no overall compilation of organ weight data is available. Importantly, organ weight change is an endpoint used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. Furthermore, physiologically based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from NCI/NTP studies in order to develop age-specific distributions. Results show that organ weights were collected more frequently in NCI/NTP studies at 2-wk (60 studies), 3-mo (147 studies), and 15-mo (40 studies) intervals than at other intervals, and more frequently from feeding and inhalation than drinking water studies. Liver, right kidney, lung, heart, thymus, and brain weights were most frequently collected. From the collected data, the mean and standard deviation for absolute and relative organ weights were calculated. Results show age-related increases in absolute liver, right kidney, lung, and heart weights and relatively stable brain and right testis weights. The results suggest a general variability trend in absolute organ weights of brain < right testis < right kidney < heart < liver < lung < spleen < thymus. This report describes the results of this effort.

Crigler-Najjar syndrome

MedlinePlus

... Najjar); Arias syndrome (type II Crigler-Najjar) Images Liver anatomy References Lidofsky SD. Jaundice. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

The analysis of factors affecting the threshold on repeated 18F-FDG-PET/CT investigations measured by the PERCIST protocol in patients with esophageal carcinoma.

PubMed

Fencl, Pavel; Belohlavek, Otakar; Harustiak, Tomas; Zemanova, Milada

2012-11-01

When applying the PET Response Criteria in Solid Tumors protocol, a threshold value based on standardized uptake value corrected to lean body mass (SUL) in liver parenchyma, or in the blood pool, is used: to metabolically specify a measurable lesion; to calculate metabolic tumor volume (mTV) and its product total lesion glycolysis (TLG); and as a limit for response measurement. The problem with using changes in glucose metabolism as a marker for response to therapy is its reproducibility on test-retest examinations. Therefore, before the evaluation of tumor treatment response, we verified our diagnostic protocol for homogeneity using the PET Response Criteria in Solid Tumors quality parameters. In addition, we analyzed the effect of the time span between examinations on the average value of SUL (SUL MEAN) in liver parenchyma at three different points: first at baseline (BL), after the first course of chemotherapy (ChT1), and finally after finishing therapy (ChT3). We also analyzed the influence of SUL MEAN variation on mTV and TLG. Eighty-four patients with esophageal cancer were prospectively examined at BL using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG)-PET/CT; 53 of 84 patients were examined after ChT1, 47 of 84 after ChT3, and 41 of 84 underwent all three examinations. Coefficient of variance (CV) and relative differences (RDw) were assessed for test-retest liver SUL values. The influence of liver SUL MEAN to mTV and TLG was modeled on BL examinations by artificial changes in liver SUL MEAN by ± 20%. No significant differences were found in test-retest liver SUL MEAN values. Comparing BL with ChT1, BL with ChT3, and ChT1 with ChT3, the CV of the liver SUL MEAN was 10.4, 10.7, and 10.3%; nevertheless, in 34.0, 38.3, and 36.6% of these examinations, respectively, the liver average SUL MEAN values exceeded the limit for inclusion in the study; that is, the difference was less than ± 0.3 U and ± 20%. The corresponding CV of blood background was 14.9, 16.5, and 17.2%. The artificial decrease of -20% in the liver SUL MEAN resulted in an increase of +43.6% in mTV and of +20.4% in TLG, whereas an increase of +20% in the liver SUL MEAN resulted in a decrease of -20.6% in mTV and -11.9% in TLG. SUL MEAN values in reference tissues (liver parenchyma or descending aorta) measured before chemotherapy did not differ significantly from those measured during chemotherapy. The CV of liver SUL MEAN was comparable to that seen in published data, but some patients had to be excluded from the study because of the individual variability of their mean liver SUL MEAN, which consequently hinders the clinical usage of mTV and TLG. Even in the standardized protocol, all potential sources of variability should be minimized.

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure.

PubMed

Roberts, Dean W; Lee, William M; Hinson, Jack A; Bai, Shasha; Swearingen, Christopher J; Stravitz, R Todd; Reuben, Adrian; Letzig, Lynda; Simpson, Pippa M; Rule, Jody; Fontana, Robert J; Ganger, Daniel; Reddy, K Rajender; Liou, Iris; Fix, Oren; James, Laura P

2017-04-01

A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal-Wallis test or rank-sum test for continuous variables. AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222-1027) vs 3678 (range, 394-8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non-acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Defining a reference set to support methodological research in drug safety.

PubMed

Ryan, Patrick B; Schuemie, Martijn J; Welebob, Emily; Duke, Jon; Valentine, Sarah; Hartzema, Abraham G

2013-10-01

Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability.

Genetics Home Reference: progressive familial intrahepatic cholestasis

MedlinePlus

... the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly). There ... Manual Consumer Version: Cholestasis Merck Manual Consumer Version: Portal Hypertension Orphanet: Progressive familial intrahepatic cholestasis Patient Support and ...

Genetics Home Reference: non-alcoholic fatty liver disease

MedlinePlus

... different populations of microorganisms in the intestines (gut microbiota) on the breakdown and absorption of nutrients are ... Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background. Gastroenterol Res Pract. 2016;2016: ...

Image quality comparison of two adaptive statistical iterative reconstruction (ASiR, ASiR-V) algorithms and filtered back projection in routine liver CT.

PubMed

Chen, Li-Hong; Jin, Chao; Li, Jian-Ying; Wang, Ge-Liang; Jia, Yong-Jun; Duan, Hai-Feng; Pan, Ning; Guo, Jianxin

2018-06-06

To compare image quality of two adaptive statistical iterative reconstruction (ASiR and ASiR-V) algorithms using objective and subjective metrics for routine liver CT, with the conventional filtered back projection (FBP) reconstructions as reference standards. This institutional review board-approved study included 52 patients with clinically suspected hepatic metastases. Patients were divided equally into ASiR and ASiR-V groups with same scan parameters. Images were reconstructed with ASiR and ASiR-V from 0 (FBP) to 100% blending percentages at 10% interval in its respective group. Mean and standard deviation of CT numbers for liver parenchyma were recorded. Two experienced radiologists reviewed all images for image quality blindly and independently. Data were statistically analyzed. There was no difference in CT dose index between ASiR and ASiR-V groups. As the percentage of ASiR and ASiR-V increased from 10 to 100% , image noise reduced by 8.6 -57.9% and 8.9-81.6%, respectively, compared with FBP. There was substantial interobserver agreement in image quality assessment for ASiR and ASiR-V images. Compared with FBP reconstruction, subjective image quality scores of ASiR and ASiR-V improved significantly as percentage increased from 10 to 80% for ASiR (peaked at 50% with 32.2% noise reduction) and from 10 to 90% (peaked at 60% with 51.5% noise reduction) for ASiR-V. Both ASiR and ASiR-V improved the objective and subjective image quality for routine liver CT compared with FBP. ASiR-V provided further image quality improvement with higher acceptable percentage than ASiR, and ASiR-V60% had the highest image quality score. Advances in knowledge: (1) Both ASiR and ASiR-V significantly reduce image noise compared with conventional FBP reconstruction. (2) ASiR-V with 60 blending percentage provides the highest image quality score in routine liver CT.

Segmentation of hepatic artery in multi-phase liver CT using directional dilation and connectivity analysis

NASA Astrophysics Data System (ADS)

Wang, Lei; Schnurr, Alena-Kathrin; Zidowitz, Stephan; Georgii, Joachim; Zhao, Yue; Razavi, Mohammad; Schwier, Michael; Hahn, Horst K.; Hansen, Christian

2016-03-01

Segmentation of hepatic arteries in multi-phase computed tomography (CT) images is indispensable in liver surgery planning. During image acquisition, the hepatic artery is enhanced by the injection of contrast agent. The enhanced signals are often not stably acquired due to non-optimal contrast timing. Other vascular structure, such as hepatic vein or portal vein, can be enhanced as well in the arterial phase, which can adversely affect the segmentation results. Furthermore, the arteries might suffer from partial volume effects due to their small diameter. To overcome these difficulties, we propose a framework for robust hepatic artery segmentation requiring a minimal amount of user interaction. First, an efficient multi-scale Hessian-based vesselness filter is applied on the artery phase CT image, aiming to enhance vessel structures with specified diameter range. Second, the vesselness response is processed using a Bayesian classifier to identify the most probable vessel structures. Considering the vesselness filter normally performs not ideally on the vessel bifurcations or the segments corrupted by noise, two vessel-reconnection techniques are proposed. The first technique uses a directional morphological operator to dilate vessel segments along their centerline directions, attempting to fill the gap between broken vascular segments. The second technique analyzes the connectivity of vessel segments and reconnects disconnected segments and branches. Finally, a 3D vessel tree is reconstructed. The algorithm has been evaluated using 18 CT images of the liver. To quantitatively measure the similarities between segmented and reference vessel trees, the skeleton coverage and mean symmetric distance are calculated to quantify the agreement between reference and segmented vessel skeletons, resulting in an average of 0:55+/-0:27 and 12:7+/-7:9 mm (mean standard deviation), respectively.

APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis.

PubMed

El Serafy, Magdy Amin; Kassem, Abdel Meguid; Omar, Heba; Mahfouz, Mohammad Shaaban; El Said El Raziky, Maissa

2017-06-01

Hepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis. Systematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients. Both APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851-0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59-0.78, p-value; 0.001). APRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

A new formula for estimation of standard liver volume using computed tomography-measured body thickness.

PubMed

Ma, Ka Wing; Chok, Kenneth S H; Chan, Albert C Y; Tam, Henry S C; Dai, Wing Chiu; Cheung, Tan To; Fung, James Y Y; Lo, Chung Mau

2017-09-01

The objective of this article is to derive a more accurate and easy-to-use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donor's body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25-13.60; P < 0.01) and body thickness (OR, 2.00; 95% CI, 0.36-3.65; P = 0.02) were found to be independent factors for the TLV calculation. A formula for TLV (cm 3 ) was derived: 2 × thickness (mm) + 10 × weight (kg) + 190 with R 2 0.48, which was the highest when compared with the 4 other most often cited formulas. This formula remained superior to other published formulas in the validation set analysis (R 2 , 5.37; interclass correlation coefficient, 0.74). Graft weight/ESLV values calculated by the new formula were shown to have the highest correlation with delayed graft function (C-statistic, 0.79; 95% CI, 0.69-0.90; P < 0.01). The new formula (2 × thickness + 10 × weight + 190) represents the first study proposing the use of CT-measured body thickness which is novel, easy to use, and the most accurate for ESLV. Liver Transplantation 23 1113-1122 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Quantitative PET of liver functions

PubMed Central

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Quantitative PET of liver functions.

PubMed

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

Chronic hepatitis C and liver fibrosis

PubMed Central

Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

2014-01-01

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy. PMID:25170193

Applicability and variability of liver stiffness measurements according to probe position

PubMed Central

Ingiliz, Patrick; Chhay, Kim Pav; Munteanu, Mona; Lebray, Pascal; Ngo, Yen; Roulot, Dominique; Benhamou, Yves; Thabut, Dominique; Ratziu, Vlad; Poynard, Thierry

2009-01-01

AIM: To investigate the liver stiffness measurement (LSM) applicability and variability with reference to three probe positions according to the region of liver biopsy. METHODS: The applicability for LSM was defined as at least 10 valid measurements with a success rate greater than 60% and an interquartile range/median LSM < 30%. The LSM variability compared the inter-position concordance and the concordance with FibroTest. RESULTS: Four hundred and forty two consecutive patients were included. The applicability of the anterior position (81%) was significantly higher than that of the reference (69%) and lower positions (68%), (both P = 0.0001). There was a significant difference (0.5 kPa, 95% CI 0.13-0.89; P < 0.0001) between mean LSM estimated at the reference position (9.3 kPa) vs the anterior position (8.8 kPa). Discordance between positions was associated with thoracic fold (P = 0.008). The discordance rate between the reference position result and FibroTest was higher when the 7.1 kPa cutoff was used to define advanced fibrosis instead of 8.8 kPa (33.6% vs 23.5%, P = 0.03). CONCLUSION: The anterior position of the probe should be the first choice for LSM using Fibroscan, as it has a higher applicability without higher variability compared to the usual liver biopsy position. PMID:19610141

Genetics Home Reference: glycogen storage disease type VI

MedlinePlus

... glucose, a simple sugar that is the main energy source for most cells in the body. PYGL gene mutations prevent liver glycogen phosphorylase from breaking down glycogen ... energy, resulting in ketosis. Glycogen accumulates within liver cells, ...

A case report of pancreatic transection by blunt abdominal trauma.

PubMed

Braşoveanu, V; Bălescu, I; Anghel, C; Barbu, I; Ionescu, M; Bacalbaşa, N

2014-01-01

Posttraumatic pancreatic rupture is associated with high morbidity and mortality. Various management strategies are described, but due to the relative rarity of this pathology no standards exist. We reported a 21 years old male with post traumatic complete rupture of the pancreatic isthmus,devascularization lesion of descending duodenum, right renal artery posttraumatic thrombosis and left lobe of the liver laceration. Laparotomy for hemostasis was initially performed in a different hospital and the patient was then referred to us.Pancreaticoduodenectomy and right nephrectomy were performed. Postoperatively the patient had a pancreaticojejunal anastomosis fistula spontaneously resolved at 45 days.Pancreaticoduodenectomy can in selected cases be a solution in pancreatic trauma. Celsius.

Diagnostic Accuracy of Preoperative Gadoxetic Acid–enhanced 3-T MR Imaging for Malignant Liver Lesions by Using Ex Vivo MR Imaging–matched Pathologic Findings as the Reference Standard1

PubMed Central

Costa, Eduardo A. C.; Cunha, Guilherme M.; Smorodinsky, Emmanuil; Cruite, Irene; Tang, An; Marks, Robert M.; Clark, Lisa; Wolfson, Tanya; Gamst, Anthony; Sicklick, Jason K.; Hemming, Alan; Peterson, Michael R.; Middleton, Michael S.; Sirlin, Claude B.

2016-01-01

Purpose To determine per-lesion sensitivity and positive predictive value (PPV) of gadoxetic acid–enhanced 3-T magnetic resonance (MR) imaging for the diagnosis of malignant lesions by using matched (spatially correlated) hepatectomy pathologic findings as the reference standard. Materials and Methods In this prospective, institutional review board–approved, HIPAA-compliant study, 20 patients (nine men, 11 women; mean age, 59 years) with malignant liver lesions who gave written informed consent underwent preoperative gadoxetic acid–enhanced 3-T MR imaging for surgical planning. Two image sets were independently analyzed by three readers to detect liver lesions (set 1 without and set 2 with hepatobiliary phase [HBP] images). Hepatectomy specimen ex vivo MR imaging assisted in matching gadoxetic acid–enhanced 3-T MR imaging findings with pathologic findings. Interreader agreement was assessed by using the Cohen k coefficient. Per-lesion sensitivity and PPV were calculated. Results Cohen k values were 0.64–0.76 and 0.57–0.84, and overall per-lesion sensitivity was 45% (42 of 94 lesions) to 56% (53 of 94 lesions) and 58% (55 of 94 lesions) to 64% (60 of 94 lesions) for sets 1 and 2, respectively. The addition of HBP imaging did not affect interreader agreement but significantly improved overall sensitivity for one reader (P < .05) and almost for another (P = .05). Sensitivity for 0.2–0.5-cm lesions was 0% (0 of 26 lesions) to 8% (two of 26 lesions) for set 1 and 4% (one of 26 lesions) to 12% (three of 26 lesions) for set 2. Sensitivity for 0.6–1.0-cm lesions was 28% (nine of 32 lesions) to 59% (19 of 32 lesions) for set 1 and 66% (21 of 32 lesions) to 69% (22 of 32 lesions) for set 2. Sensitivity for lesions at least 1.0 cm in diameter was at least 81% (13 of 16 lesions) for set 1 and was not improved for set 2. PPV was 98% (56 of 57 lesions) to 100% (60 of 60 lesions) for all readers without differences between image sets or lesion size. Conclusion Gadoxetic acid–enhanced 3-T MR imaging provides high per-lesion sensitivity and PPV for preoperative malignant liver lesion detection overall, although sensitivity for 0.2–0.5-cm malignant lesions is poor. PMID:25875972

Results of percutaneous sclerotherapy and surgical treatment in patients with symptomatic simple liver cysts and polycystic liver disease

PubMed Central

Erdogan, Deha; van Delden, Otto M; Rauws, Erik AJ; Busch, Olivier RC; Lameris, Johan S; Gouma, Dirk J; van Gulik, Thomas M

2007-01-01

AIM: To evaluate the results of the treatment of simple liver cysts (solitary and multiple) and polycystic liver disease (PLD) using percutaneous sclerotherapy and/or surgical procedures in a single tertiary referral centre. METHODS: Retrospective analysis of 54 patients referred for evaluation and possible treatment of simple liver cysts (solitary and multiple) and PLD, from January 1997 to July 2006. RESULTS: Simple liver cysts were treated in 41 pts (76%) with a mean size of 12.6 cm. The most common reason for referral was abdominal pain or discomfort (85%). Percutaneous sclerotherapy was performed as initial treatment in 30 pts, showing cyst recurrence in 6 pts (20%). Surgical treatment was initially performed in 11 pts with cyst recurrence in 3 pts (27%). PLD was treated in 13 pts (24%) with a mean size of the dominant cyst of 13 cm. Percutaneous sclerotherapy for PLD was performed in 9 pts with recurrence in 7 pts (77.8%). Surgical treatment for PLD was undertaken in 4 pts (30.8%) with recurrence in all. Eventually, 2 pts with PLD in the presence of polycystic kidney disease underwent liver- and kidney transplantation because of deterioration of liver and kidney function. CONCLUSION: The majority of patients with simple liver cysts and PLD are referred for progressive abdominal pain. As initial treatment, percutaneous sclerotherapy is appropriate. Surgical deroofing is indicated in case of cyst recurrence after percutaneous sclerotherapy. However, the results of percutaneous sclerotherapy and surgical treatment for PLD are disappointing. Partial liver resection is indicated when there is suspicion of a pre-malignant lesion. PMID:17589926

Simultaneous multislice diffusion-weighted MRI of the liver: Analysis of different breathing schemes in comparison to standard sequences.

PubMed

Taron, Jana; Martirosian, Petros; Erb, Michael; Kuestner, Thomas; Schwenzer, Nina F; Schmidt, Holger; Honndorf, Valerie S; Weiβ, Jakob; Notohamiprodjo, Mike; Nikolaou, Konstantin; Schraml, Christina

2016-10-01

To systematically evaluate image characteristics of simultaneous-multislice (SMS)-accelerated diffusion-weighted imaging (DWI) of the liver using different breathing schemes in comparison to standard sequences. DWI of the liver was performed in 10 healthy volunteers and 12 patients at 1.5T using an SMS-accelerated echo planar imaging sequence performed with respiratory-triggering and free breathing (SMS-RT, SMS-FB). Standard DWI sequences served as reference (STD-RT, STD-FB). Reduction of scan time by SMS-acceleration was measured. Image characteristics of SMS-DWI and STD-DWI with both breathing schemes were analyzed quantitatively (apparent diffusion coefficient [ADC], signal-to-noise ratio [SNR]) and qualitatively (5-point Likert scale, 5 = excellent). Qualitative and quantitative parameters were compared using Friedman test and Dunn-Bonferroni post-hoc method with P-values < 0.05 considered statistically significant. SMS-DWI provided diagnostic image quality in volunteers and patients both with RT and FB with a reduction of scan time of 70% (0:56 vs. 3:20 min in FB). Overall image quality did not significantly differ between FB and RT acquisition in both STD and SMS sequences (median STD-RT 5.0, STD-FB 4.5, SMS-RT: 4.75; SMS-FB: 4.5; P = 0.294). SNR in the right hepatic lobe was comparable between the four tested sequences. ADC values were significantly lower in SMS-DWI compared to STD-DWI irrespective of the breathing scheme (1.2 ± 0.2 × 10(-3) mm(2) /s vs. 1.0 ± 0.2 × 10(-3) mm(2) /s; P < 0.001). SMS-acceleration provides considerable scan time reduction for hepatic DWI with equivalent image quality compared to the STD technique both using RT and FB. Discrepancies in ADC between STD-DWI and SMS-DWI need to be considered when transferring the SMS technique to clinical routine reading. J. MAGN. RESON. IMAGING 2016;44:865-879. © 2016 International Society for Magnetic Resonance in Medicine.

Toward Current Standards of Donor Right Hepatectomy for Adult-to-Adult Live Donor Liver Transplantation Through the Experience of 200 Cases

PubMed Central

Chan, See Ching; Fan, Sheung Tat; Lo, Chung Mau; Liu, Chi Leung; Wong, John

2007-01-01

Objective: To define the current standards of donor right hepatectomy, including the middle hepatic vein for adult-to-adult live donor liver transplantation. Summary Background Data: Donor morbidity and mortality are inevitable given the ultra-major nature of the donor operation. Results from a matured center could define the true impact of this donor procedure most accurately. Patients and Methods: From May 9, 1996 to April 13, 2005, 200 consecutive donors underwent donor right hepatectomy at the University of Hong Kong Medical Center. All right liver grafts except one included the middle hepatic vein. Donor characteristics, operation time, blood loss, hospital stay, laboratory results, and complications graded by Clavien's classification divided into four eras (each consecutive 50 cases) were compared. Results: Donor characteristics of the four eras were generally comparable. Operative outcomes improved progressively through the four eras. From era 1 to era 4, operation time decreased from 598 minutes (range, 378–932 minutes) to 391 minutes (range, 304–635 minutes). Blood loss also decreased from 500 mL (200–1600 mL) of era 1 to 251 mL (range, 95–595 mL) of era 4. Overall complication rate was 20.5% (41 of 200). Complications rates from eras 1 to 4 were 34%, 16%, 16%, and 16%, respectively. The most common complications were of grade I (24 of 41, 58.5%). A late donor death occurred in era 4 from the development of a duodenocaval fistula 10 weeks postoperation, giving a donor mortality of 0.5% (1 of 200). Conclusions: This study validated the estimated morbidity and mortality of donor right hepatectomy of 20% and 0.5%, respectively. The data provide reference for counseling potential donors and setting the standards of donor right hepatectomy in the current era. PMID:17197973

[Analysis of liver cancer incidence and trend in China].

PubMed

Zuo, Tingting; Zheng, Rongshou; Zeng, Hongmei; Zhang, Siwei; Chen, Wanqing

2015-09-01

The national population-based cancer registration data were used to analyze the liver cancer incidence and trend in China, in order to provide advise for making further strategy on liver cancer prevention and control. Liver cancer data of 2011 were retrieved from the database of the National Cancer Registry. The incident cases of liver cancer were estimated using age-specific rate by urban or rural areas and gender according to the national population in 2011. Liver cancer incidence data from 22 cancer registries were used to analyze the incidence trend during 2000-2011. The estimates of new cases of liver cancer were about 356 thousand in China in 2011. The incidence rate was 26.39/10(5,) and the age-standardized incidence rates by Chinese standard population and by world population were 19.48/10(5) and 19.10/10(5,) respectively.There was an increasing trend of incidence rate of liver cancer in China during 2000-2011 with an average annual percentage change(AAPC) of 1.0% (95%CI: 0.5%-1.4%), 1.2% (95%CI: 0.7%-1.8%)in urban areas and 1.1% (95%CI: 0.5%-1.8%) in rural areas. After age standardization, the incidence rate was significantly decreased, with an AAPC of -1.8% (95%CI: -2.4% to -1.2%), -1.6% (95%CI: -2.2% to -0.9%) in urban and -1.4% (95%CI: -2.5% to -0.3%) in rural areas. Liver cancer is a common cancer in China. As changing in people's dietary habits and implementing neonatal HBV vaccination for years, the exposure to risk factors is reducing, and age-standardized incidence rate is decreasing. While cardinal number of population is big and aging population is growing rapidly in the country, trend of incidence rate is increasing, and the burden of liver cancer is still high in China.

Validation of graft and standard liver size predictions in right liver living donor liver transplantation.

PubMed

Chan, See Ching; Lo, Chung Mau; Chok, Kenneth S H; Sharr, William W; Cheung, Tan To; Tsang, Simon H Y; Chan, Albert C Y; Fan, Sheung Tat

2011-12-01

To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, ( R 2  = 0.476) ( p  = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively ( R 2  = 0.781) ( p  = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. SLV and graft weight estimations were accurate using the formula and conversion factor.

Genetics Home Reference: dihydrolipoamide dehydrogenase deficiency

MedlinePlus

... begin anytime from infancy to adulthood, is the primary symptom. The liver problems are usually associated with recurrent vomiting and ... of Ashkenazi Jewish descent. This population typically has liver disease as the primary symptom. In other populations, the prevalence of dihydrolipoamide ...

Use and dissemination of the brisbane 2000 nomenclature of liver anatomy and resections.

PubMed

Strasberg, Steven M; Phillips, Carolyn

2013-03-01

The Brisbane 2000 Nomenclature of Hepatic Anatomy and Resections was created to standardize terminology in an area, which previously was characterized by redundant and confusing terms. The purpose of this study was to evaluate the use and dissemination of the nomenclature 10 years after its introduction. Two strategies were used to evaluate implementation of the terminology. The first depended on an examination of terms used to describe the anatomy and resection of one half of the liver over the 20-year period from 1990 to 2009. The second approach evaluated the use of the terms "section," "sectionectomy," and "trisectionectomy," which, in reference to the liver, are unique to the Brisbane 2000 Nomenclature. The use of the Brisbane 2000 terms "right and left hemihepatectomy/hepatectomy" increased dramatically versus the use of the discarded terms "right and left hepatic lobectomy" after the Nomenclature was introduced in 2000. This was especially true in the Americas and Asia where the terms were used in less than 50% of papers from 1990 to 1999 but reached 80% utilization by 2006. Likewise, use of the terms "section," "sectionectomy," and "trisectionectomy" increased sharply especially in between 2006 and 2009. The Brisbane terminology is being adopted worldwide but its adoption is still incomplete.

[Determination of trace Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS].

PubMed

Wang, Jing-yu; Zhu, Hong-da; Ouyang, Li; Liu, Ya-qiong; Wang, Xiao-yan; Huang, Zhuo; Wang, Nai-fen; Liu, Hu-sheng

2004-09-01

This paper studied the trace elements Cs, Th and U in ten kinds of human autopsy tissues by ICP-MS. The instrumental operating conditions were optimized for the measurement of Cs, Th and U. Rhodium (Rh) was used as an internal standard element to compensate matrix effect. Detection limits for Th, U and Cs were 5.7-17.8 pg x mL(-1). The recoveries for spiking liver samples were 96%-107%, and their RSDs were 4.8%-8.9%. Reference materials of NIST SRM 8414 Bovine and NIST SRM 1486 Bone Meal were analyzed by the described method, and the analytical results agreed well with the reference values. Human autopsy tissues samples were digested by mixed acid (HNO3 + HClO4). The determination of Cs, Th and U in lung, liver, bone, heart, stomach, spleen, muscle, kidney, thyroid gland and intestinum tenue was performed by ICP-MS without separation and enrichment procedures. The obtained results indicated that this method is rapid, sensitive and accurate; the distribution of the three elements is different from one to another human organ sample; the main organ targets for Th and U are lungs and kidneys; and a coordinated variation of Cs, Th and U concentration in lungs was found in the samples collected from Hebei and Sichuan provinces.

Elemental concentrations in kidney and liver of mice fed with cafeteria or standard diet determined by particle induced X-ray emission

NASA Astrophysics Data System (ADS)

Leffa, Daniela Dimer; dos Santos, Carla Eliete Iochims; Debastiani, Rafaela; Amaral, Livio; Yoneama, Maria Lucia; Dias, Johnny Ferraz; Andrade, Vanessa Moraes

2014-01-01

The importance of trace elements in human health is well known and their main source is daily diet. Nowadays, one of the biggest issues is the presence of these micronutrients in levels much higher than required, leading to potential toxic effects. The aim of this work was to investigate the elemental content in organs of mice fed with cafeteria or standard diet using PIXE. Twelve male Swiss mice were divided into two groups: control group (standard chow) and cafeteria group (high-caloric diet). After 17 weeks, samples of different organs (kidney and liver) were collected and prepared for PIXE analysis. The Fe concentration in kidney and liver was statistically higher in animals that received the cafeteria diet (p < 0.001). The Al and Si kidney contents were significantly higher for cafeteria diet in relation to standard diet (p < 0.05). Moreover, the standard diet showed significant differences for Cl and K (p < 0.05) in comparison to cafeteria diet in kidney, and for P, S and Zn (p < 0.005) in liver.

Systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection based on Laennec's capsule: proposal of a novel comprehensive surgical anatomy of the liver

PubMed Central

Sugioka, Atsushi; Kato, Yutaro; Tanahashi, Yoshinao

2017-01-01

Abstract Anatomical liver resection with the Glissonean pedicle isolation is widely approved as an essential procedure for safety and curability. Especially, the extrahepatic Glissonean pedicle isolation without parenchymal destruction should be an ideal procedure. However, the surgical technique has not been standardized due to a lack of anatomical understanding. Herein, we proposed a novel comprehensive surgical anatomy of the liver based on Laennec's capsule that would give a theoretical background to the extrahepatic Glissonean pedicle isolation. Laennec's capsule is the proper membrane that covers not only the entire surface of the liver including the bare area but also the intrahepatic parenchyma surrounding the Glissonean pedicles. Consequently, there exists a gap between the Glissonean pedicle and Laennec's capsule that could be reached extrahepatically and allows us to isolate the extrahepatic Glissonean pedicle without parenchymal destruction systematically. For standardization, it is essential to approach the “six gates” indicated by the “four anatomical landmarks”: the Arantius plate, the umbilical plate, the cystic plate and the Glissonean pedicle of the caudate process (G1c). This novel anatomy would contribute to standardize the surgical techniques of the systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection including laparoscopic or robotic liver resection and to bring innovative changes in hepatobiliary surgery for spreading safe and curable liver resection. PMID:28156078

Estimation of standard liver volume in Chinese adult living donors.

PubMed

Fu-Gui, L; Lu-Nan, Y; Bo, L; Yong, Z; Tian-Fu, W; Ming-Qing, X; Wen-Tao, W; Zhe-Yu, C

2009-12-01

To determine a formula predicting the standard liver volume based on body surface area (BSA) or body weight in Chinese adults. A total of 115 consecutive right-lobe living donors not including the middle hepatic vein underwent right hemi-hepatectomy. No organs were used from prisoners, and no subjects were prisoners. Donor anthropometric data including age, gender, body weight, and body height were recorded prospectively. The weights and volumes of the right lobe liver grafts were measured at the back table. Liver weights and volumes were calculated from the right lobe graft weight and volume obtained at the back table, divided by the proportion of the right lobe on computed tomography. By simple linear regression analysis and stepwise multiple linear regression analysis, we correlated calculated liver volume and body height, body weight, or body surface area. The subjects had a mean age of 35.97 +/- 9.6 years, and a female-to-male ratio of 60:55. The mean volume of the right lobe was 727.47 +/- 136.17 mL, occupying 55.59% +/- 6.70% of the whole liver by computed tomography. The volume of the right lobe was 581.73 +/- 96.137 mL, and the estimated liver volume was 1053.08 +/- 167.56 mL. Females of the same body weight showed a slightly lower liver weight. By simple linear regression analysis and stepwise multiple linear regression analysis, a formula was derived based on body weight. All formulae except the Hong Kong formula overestimated liver volume compared to this formula. The formula of standard liver volume, SLV (mL) = 11.508 x body weight (kg) + 334.024, may be applied to estimate liver volumes in Chinese adults.

Feasibility and Diagnostic Accuracy of Supersonic Shear-Wave Elastography for the Assessment of Liver Stiffness and Liver Fibrosis in Children: A Pilot Study of 96 Patients.

PubMed

Franchi-Abella, Stéphanie; Corno, Lucie; Gonzales, Emmanuel; Antoni, Guillemette; Fabre, Monique; Ducot, Béatrice; Pariente, Danièle; Gennisson, Jean-Luc; Tanter, Mickael; Corréas, Jean-Michel

2016-02-01

To evaluate the feasibility of using supersonic shear-wave elastography (SSWE) in children and normal values of liver stiffness with the use of control patients of different ages (from neonates to teenagers) and the diagnostic accuracy of supersonic shear wave elastography for assessing liver fibrosis by using the histologic scoring system as the reference method in patients with liver disease, with a special concern for early stages of fibrosis. The institutional review board approved this prospective study. Informed consent was obtained from parents and children older than 7 years. First, 51 healthy children (from neonate to 15 years) were analyzed as the control group, and univariate and multivariate comparisons were performed to study the effect of age, transducer, breathing condition, probe, and position on elasticity values. Next, 45 children (from 1 month to 17.2 years old) who underwent liver biopsy were analyzed. SSWE measurements were obtained in the same region of the liver as the biopsy specimens. Biopsy specimens were reviewed in a blinded manner by a pathologist with the use of METAVIR criteria. The areas under the receiver operating characteristics curve (AUCs) were calculated for patients with fibrosis stage F0 versus those with stage F1-F2, F2 or higher, F3 or higher, and F4 or higher. A successful rate of SSWE measurement was 100% in 96 patients, including neonates. Liver stiffness values were significantly higher when an SC6-1 probe (Aixplorer; SuperSonic Imagine SA, Aix-enProvence, France) was used than when an SL15-4 probe (Aixplorer) was used (mean ± standard deviation, 6.94 kPa ± 1.42 vs 5.96 kPa ± 1.31; P = .006). There was no influence of sex, the location of measurement, or respiratory status on liver elasticity values (P = .41-.93), although the power to detect such a difference was low. According to the degree of liver fibrosis at liver biopsy, 88.5%-96.8% of patients were correctly classified, with AUCs of 0.90-0.98 (95% confidence interval [CI]: 0.8, 1.0). The AUC for patients with stage F0 versus stage F1-F2 was 0.93 (95% CI: 0.87, 0.99). SSWE allows accurate assessment of liver fibrosis, even in children with early stage (F1-F2) disease, and the choice of transducer influences liver stiffness values. © RSNA, 2015.

Expression and purification of a functional recombinant aspartate aminotransferase (AST) from Escherichia coli.

PubMed

Zou, Lihui; Zhao, Haijian; Wang, Daguang; Wang, Meng; Zhang, Chuanbao; Xiao, Fei

2014-07-01

Aspartate aminotransferase (AST; E.C. 2.6.1.1), a vitamin B6-dependent enzyme, preferentially promotes the mutual transformation of aspartate and α-ketoglutarate to oxaloacetate and glutamate. It plays a key role in amino acid metabolism and has been widely recommended as a biomarker of liver and heart damage. Our study aimed to evaluate the extensive preparation of AST and its application in quality control in clinical laboratories. We describe a scheme to express and purify the 6His-AST fusion protein. An optimized sequence coding AST was synthesized and transformed into Escherichia coli BL21 (DE3) strain for protein expression. Ideally, the fusion protein has a volumetric productivity achieving 900 mg/l cultures. After affinity chromatography, the enzyme activity of purified AST reached 150,000 U/L. Commutability assessment between the engineered AST and standard AST from Roche suggested that the engineered AST was the better candidate for the reference material. Moreover, the AST showed high stability during long-term storage at -20ºC. In conclusion, the highly soluble 6His-tagged AST can become a convenient tool for supplying a much better and cheaper standard or reference material for the clinical laboratory.

Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

NASA Astrophysics Data System (ADS)

Oudry, Jennifer; Lynch, Ted; Vappou, Jonathan; Sandrin, Laurent; Miette, Véronique

2014-10-01

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young’s modulus over the range of normal and cirrhotic liver stiffnesses. The Young’s modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

PubMed

Oudry, Jennifer; Lynch, Ted; Vappou, Jonathan; Sandrin, Laurent; Miette, Véronique

2014-10-07

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young's modulus over the range of normal and cirrhotic liver stiffnesses. The Young's modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

Analysis of LIF-Raman spectroscopy for the diagnosis of normal and liver diseases

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Yang, Tianyue; Yu, Ting; Sun, Ruomin; Li, Siqi

2011-07-01

In this paper, 514.5nm argon ion laser induced human serum Raman and auto-fluorescence spectra of normal, liver cirrhosis and liver cancer were measured and analyzed. The spectral differences between these three types of serums were observed and given brief explanations. Three parameters α, φ and Δλ were introduced to describe characteristics of each type of spectrum. Experimental results showed that these parameters might be applicable for discrimination of normal, liver cirrhosis and liver cancer, which will provide some reference values to explore the method of laser spectral diagnosis of cancer.

Functional liver image guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans.

PubMed

Long, David E; Tann, Mark; Huang, Ke Colin; Bartlett, Gregory; Galle, James O; Furukawa, Yukie; Maluccio, Mary; Cox, John A; Kong, Feng-Ming Spring; Ellsworth, Susannah G

2018-05-01

Hepatobiliary iminodiacetic acid (HIDA) scans provide global and regional assessments of liver function that can serve as a road map for functional avoidance in stereotactic body radiation therapy (SBRT) planning. Functional liver image guided hepatic therapy (FLIGHT), an innovative planning technique, is described and compared with standard planning using functional dose-volume histograms. Thresholds predicting for decompensation during follow up are evaluated. We studied 17 patients who underwent HIDA scans before SBRT. All SBRT cases were replanned using FLIGHT. The following dosimetric endpoints were compared for FLIGHT versus standard SBRT planning: functional residual capacity <15 Gy (FRC 15 HIDA), mean liver dose (MLD), equivalent uniform dose (EUD), and functional EUD (FEUD). Receiver operating characteristics curves were used to evaluate whether baseline HIDA values, standard cirrhosis scoring, and/or dosimetric data predicted clinical decompensation. Compared with standard planning, FLIGHT significantly improved FRC 15 HIDA (mean improvement: 5.3%) as well as MLD, EUD, and FEUD (P < .05). Considerable interindividual variations in the extent of benefit were noted. Decompensation during follow-up was associated with baseline global HIDA <2.915%/min/m 2 , FRC 15 HIDA <2.11%/min/m 2 , and MELD ≥11 (P < .05). FLIGHT with HIDA-based parameters may complement blood chemistry-based assessments of liver function and facilitate individualized, adaptive liver SBRT planning. Copyright © 2018. Published by Elsevier Inc.

Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease.

PubMed

Fedchuk, L; Nascimbeni, F; Pais, R; Charlotte, F; Housset, C; Ratziu, V

2014-11-01

Several steatosis biomarkers are available with limited independent validation. To determine diagnostic value and limitations of several steatosis biomarkers using liver biopsy as reference standard in a large cohort of patients with suspected NAFLD. Three hundred and twenty-four consecutive liver biopsies were included. Histological steatosis was categorised as none (<5%), mild (5-33%), moderate (33-66%) and severe (>66%). Five steatosis biomarkers were measured: fatty liver index (FLI), NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI), visceral adiposity index (VAI) and triglyceride × glucose (TyG) index. Steatosis grades prevalence was: none 5%, mild 39%, moderate 30% and severe 27%. Except for VAI, the steatosis biomarkers showed a linear trend across the steatosis grades. However, their correlation with the histological amount of steatosis was only weak-moderate. All steatosis biomarkers had an adequate diagnostic accuracy for the presence of steatosis: AUROCs for FLI, LFS, HSI, VAI and TyG were 0.83, 0.80, 0.81, 0.92 and 0.90. However, their ability to quantify steatosis was poor: none of them distinguished between moderate and severe steatosis and the AUROCs for predicting steatosis >33% were 0.65, 0.72, 0.65, 0.59 and 0.59 for FLI, LFS, HSI, VAI and TyG. Both fibrosis and inflammation significantly confounded the association between steatosis biomarkers and steatosis. The steatosis biomarkers were all correlated with HOMA-IR, independent from histological steatosis. All five steatosis biomarkers can diagnose steatosis and are correlated with insulin resistance. They are confounded by fibrosis and inflammation, and do not accurately quantify steatosis; this may limit their clinical utility. More research is needed to identify truly independent and quantitative markers of steatosis. © 2014 John Wiley & Sons Ltd.

Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis.

PubMed

Tang, An; Tan, Justin; Sun, Mark; Hamilton, Gavin; Bydder, Mark; Wolfson, Tanya; Gamst, Anthony C; Middleton, Michael; Brunt, Elizabeth M; Loomba, Rohit; Lavine, Joel E; Schwimmer, Jeffrey B; Sirlin, Claude B

2013-05-01

To evaluate the diagnostic performance of magnetic resonance (MR) imaging-estimated proton density fat fraction (PDFF) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) by using centrally scored histopathologic validation as the reference standard. This prospectively designed, cross-sectional, internal review board-approved, HIPAA-compliant study was conducted in 77 patients who had NAFLD and liver biopsy. MR imaging-PDFF was estimated from magnitude-based low flip angle multiecho gradient-recalled echo images after T2* correction and multifrequency fat modeling. Histopathologic scoring was obtained by consensus of the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network Pathology Committee. Spearman correlation, additivity and variance stabilization for regression for exploring the effect of a number of potential confounders, and receiver operating characteristic analyses were performed. Liver MR imaging-PDFF was systematically higher, with higher histologic steatosis grade (P < .001), and was significantly correlated with histologic steatosis grade (ρ = 0.69, P < .001). The correlation was not confounded by age, sex, lobular inflammation, hepatocellular ballooning, NASH diagnosis, fibrosis, or magnetic field strength (P = .65). Area under the receiver operating characteristic curves was 0.989 (95% confidence interval: 0.968, 1.000) for distinguishing patients with steatosis grade 0 (n = 5) from those with grade 1 or higher (n = 72), 0.825 (95% confidence interval: 0.734, 0.915) to distinguish those with grade 1 or lower (n = 31) from those with grade 2 or higher (n = 46), and 0.893 (95% confidence interval: 0.809, 0.977) to distinguish those with grade 2 or lower (n = 58) from those with grade 3 (n = 19). MR imaging-PDFF showed promise for assessment of hepatic steatosis grade in patients with NAFLD. For validation, further studies with larger sample sizes are needed. © RSNA, 2013.

Ethnic Variations in Liver- and Alcohol-Related Disease Hospitalisations and Mortality: The Scottish Health and Ethnicity Linkage Study.

PubMed

Bhala, Neeraj; Cézard, Genevieve; Ward, Hester J T; Bansal, Narinder; Bhopal, Raj

2016-09-01

Preventing alcohol-related harms, including those causing liver disease, is a public health priority in the UK, especially in Scotland, but the effects of ethnicity are not known. We assessed liver- and alcohol-related events (hospitalisations and deaths) in Scotland using self-reported measures of ethnicity. Linking Scottish NHS hospital admissions and mortality to the Scottish Census 2001, we explored ethnic differences in hospitalisations and mortality (2001-2010) of all liver diseases, alcoholic liver disease (ALD) and specific alcohol-related diseases (ARD). Risk ratios (RR) were calculated using Poisson regression with robust variance, by sex, adjusted for age, country of birth and the Scottish Index of Multiple Deprivation (SIMD) presented below. The White Scottish population was the standard reference population with 95% confidence intervals (CI) calculated to enable comparison (multiplied by 100 for results). For all liver diseases, Chinese had around 50% higher risks for men (RR 162; 95% CI 127-207) and women (141; 109-184), as did Other South Asian men (144; 104-201) and Pakistani women (140; 116-168). Lower risks for all liver diseases occurred in African origin men (42; 24-74), other White British men (72; 63-82) and women (80; 70-90) and other White women (80; 67-94). For ALD, White Irish had a 75% higher risk for men (175; 107-287). Other White British men had about a third lower risk of ALD (63; 50-78), as did Pakistani men (65; 42-99). For ARD, almost 2-fold higher risks existed for White Irish men (182; 161-206) and Any Mixed Background women (199; 152-261). Lower risks of ARD existed in Pakistani men (67; 55-80) and women (48; 33-70), and Chinese men (55; 41-73) and women (54; 32-90). Substantial variations by ethnicity exist for both alcohol-related and liver disease hospitalisations and deaths in Scotland: these exist in subgroups of both White and non-White populations and practical actions are required to ameliorate these differences. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C.

PubMed

Petersen, John R; Stevenson, Heather L; Kasturi, Krishna S; Naniwadekar, Ashutosh; Parkes, Julie; Cross, Richard; Rosenberg, William M; Xiao, Shu-Yuan; Snyder, Ned

2014-04-01

The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis. The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy from 95 to 24-a 74.7% reduction. This study has shown that the APRI and ELF tests are equally accurate in distinguishing mild from significant liver fibrosis, and combining them into a validated algorithm improves their performance in distinguishing mild from significant fibrosis.

Endocrine and metabolic dysfunction in yellow perch, Perca flavescens, exposed to organic contaminants and heavy metals in the St. Lawrence River

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hontela, A.; Duclos, D.; Fortin, R.

1995-04-01

The endocrine and biochemical responses to the acute stress of capture and handling were investigated in sexually mature and in immature male and female yellow perch, Perca flavescens, from a site contaminated by organic contaminants (PAHs and PCBs) and heavy metals (Hg, Cd, As, and Zn) and from a reference site in the St. Lawrence River. Following a standardized capture and handling stress, fish from the contaminated site did not exhibit the expected physiological stress response observed in fish from the reference site. Blood cortisol and thyroxine levels were lower, and liver glycogen stores were greater in mature males andmore » females, as well as in the immature fish from the contaminated site, compared to the reference site. Fish from the contaminated site also had smaller gonads and lower condition factor. The impaired ability to elevate blood cortisol in response to an acute stress may be used as a biomarker of toxic stress in health assessment of feral fish from polluted environments.« less

Validation of endogenous reference genes for qRT-PCR analysis of human visceral adipose samples

PubMed Central

2010-01-01

Background Given the epidemic proportions of obesity worldwide and the concurrent prevalence of metabolic syndrome, there is an urgent need for better understanding the underlying mechanisms of metabolic syndrome, in particular, the gene expression differences which may participate in obesity, insulin resistance and the associated series of chronic liver conditions. Real-time PCR (qRT-PCR) is the standard method for studying changes in relative gene expression in different tissues and experimental conditions. However, variations in amount of starting material, enzymatic efficiency and presence of inhibitors can lead to quantification errors. Hence the need for accurate data normalization is vital. Among several known strategies for data normalization, the use of reference genes as an internal control is the most common approach. Recent studies have shown that both obesity and presence of insulin resistance influence an expression of commonly used reference genes in omental fat. In this study we validated candidate reference genes suitable for qRT-PCR profiling experiments using visceral adipose samples from obese and lean individuals. Results Cross-validation of expression stability of eight selected reference genes using three popular algorithms, GeNorm, NormFinder and BestKeeper found ACTB and RPII as most stable reference genes. Conclusions We recommend ACTB and RPII as stable reference genes most suitable for gene expression studies of human visceral adipose tissue. The use of these genes as a reference pair may further enhance the robustness of qRT-PCR in this model system. PMID:20492695

Validation of endogenous reference genes for qRT-PCR analysis of human visceral adipose samples.

PubMed

Mehta, Rohini; Birerdinc, Aybike; Hossain, Noreen; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair; Baranova, Ancha

2010-05-21

Given the epidemic proportions of obesity worldwide and the concurrent prevalence of metabolic syndrome, there is an urgent need for better understanding the underlying mechanisms of metabolic syndrome, in particular, the gene expression differences which may participate in obesity, insulin resistance and the associated series of chronic liver conditions. Real-time PCR (qRT-PCR) is the standard method for studying changes in relative gene expression in different tissues and experimental conditions. However, variations in amount of starting material, enzymatic efficiency and presence of inhibitors can lead to quantification errors. Hence the need for accurate data normalization is vital. Among several known strategies for data normalization, the use of reference genes as an internal control is the most common approach. Recent studies have shown that both obesity and presence of insulin resistance influence an expression of commonly used reference genes in omental fat. In this study we validated candidate reference genes suitable for qRT-PCR profiling experiments using visceral adipose samples from obese and lean individuals. Cross-validation of expression stability of eight selected reference genes using three popular algorithms, GeNorm, NormFinder and BestKeeper found ACTB and RPII as most stable reference genes. We recommend ACTB and RPII as stable reference genes most suitable for gene expression studies of human visceral adipose tissue. The use of these genes as a reference pair may further enhance the robustness of qRT-PCR in this model system.

WE-EF-210-05: Diagnosis and Quantification of Liver Steatosis with Quantitative Ultrasound Backscatter Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andre, M; University of California, San Diego, San Diego, CA; Heba, E

2015-06-15

Purpose: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, affects 30% of adult Americans and may progress to more serious diseases. Liver biopsy is the standard method for diagnosing NAFLD. MRI can accurately diagnose and quantify hepatic steatosis but is expensive. Sonography with qualitative interpretation by radiologists is lower cost, more accessible but less sensitive for detection. The objective of this study, using MRI proton density fat fraction (PDFF) as reference, is to assess the accuracy for diagnosing and quantifying steatosis with two quantitative US parameters-- backscatter coefficient (BSC) andmore » attenuation coefficient (AC)--derived from RF signals using the calibration phantom technique. Methods: We performed a prospective, cross-sectional analysis of a cohort of adults (n=204) with NAFLD (MRI-PDFF≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and BSC and AC US analyses of the liver on the same day. Patients were randomly assigned to training (n=102, mean age 51±17 years, mean body mass index 31±7 kg/m{sup 2}) and validation (n=102, mean age 49±17 years, body mass index 30±6 kg/m{sup 2}) groups; 69% of patients in each group had NAFLD. Results: BSC provided AUC 0.98 (95% CI 0.95–1.00, p<0.0001) for diagnosis of NAFLD; the optimal BSC cut-off provided sensitivity, specificity, positive and negative predictive values (PPV, NPV) of 87%, 91%, 95%, and 76%, respectively. AC provided AUC 0.89 (95% CI 0.81–0.96, p<0.0001) for diagnosis of steatosis; the optimal AC cut-off provided sensitivity, specificity, PPV, NPV of 80%, 84%, 92%, and 66%, respectively. BSC and AC both correlated significantly with MRI-PDFF (P<0.0001). Conclusion: QUS BSC and AC can accurately diagnose and quantify hepatic steatosis, using MRI-PDFF as reference. With further validation, QUS may emerge as an inexpensive, widely available tool for NAFLD assessment. General support: NIH R01 CA111289, K23 -DK090303, AmerGastroAssoc Found, TF Williams Scholarship, S3000 scanner loaned by Siemens, Sucampo, JA Hartford Found, Atlantic Philanthropies Amer Gastroenterological Assoc. Agencies had no role in design/conduct of study, collection, management, analysis or interpretation of the data; preparation, review, or approval of the manuscript.« less

Open Liver Resection, Laparoscopic Liver Resection, and Percutaneous Thermal Ablation for Patients with Solitary Small Hepatocellular Carcinoma (≤30 mm): Review of the Literature and Proposal for a Therapeutic Strategy.

PubMed

Viganò, Luca; Laurenzi, Andrea; Solbiati, Luigi; Procopio, Fabio; Cherqui, Daniel; Torzilli, Guido

2018-06-11

Patients with a single hepatocellular carcinoma (HCC) ≤3 cm and preserved liver function have the highest likelihood to be cured if treated. The most adequate treatment methods are yet a matter that is debated. We reviewed the literature about open anatomic resection (AR), laparoscopic liver resection (LLR), and percutaneous thermal ablation (PTA). PTA is effective as resection for HCC < 2 cm, when they are neither subcapsular nor perivascular. PTA in HCC of 2-3 cm is under evaluation. AR with the removal of the tumor-bearing portal territory is recommended for HCC > 2 cm, except for subcapsular ones. In comparison with open surgery, LRR has better short-term outcomes and non-inferior long-term outcomes. LLR is standardized for superficial limited resections and for left-sided AR. According to the available evidences, the following therapeutic proposal can be advanced. Laparoscopic limited resection is the standard for any subcapsular HCC. PTA is the first-line treatment for deep-located HCC < 2 cm, except for those in contact with Glissonean pedicles. Laparoscopic AR is the standard for deep-located HCC of 2-3 cm of the left liver, while open AR is the standard for deep-located HCC of 2-3 cm in the right liver. HCC in contact with Glissonean pedicles should be scheduled for resection (open or laparoscopic) independent of their size. Liver transplantation is reserved to otherwise untreatable patients or as a salvage procedure at recurrence. © 2018 S. Karger AG, Basel.

Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?

PubMed

Costas-Rodríguez, Marta; Anoshkina, Yulia; Lauwens, Sara; Van Vlierberghe, Hans; Delanghe, Joris; Vanhaecke, Frank

2015-03-01

The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.

Measurements for certification of chlortetracycline reference materials within the European Union Standards, Measurements and Testing programme.

PubMed

Juhel-Gaugain, M; McEvoy, J D; VanGinkel, L A

2000-12-01

The experimental design of a material certification programme is described. The matrix reference materials (RMs) comprised chlortetracycline (CTC)-containing and CTC-free lyophilised porcine liver, kidney and muscle produced under the European Commission's Standards Measurements and Testing (SMT) programme. The aim of the certification programme was to determine accurately and precisely the concentration of CTC and 4-epi-chlortetracycline (epi-CTC) contained in the RMs. A multi-laboratory approach was used to certify analyte concentrations. Participants (n = 19) were instructed to strictly adhere to previously established guidelines. Following the examination of analytical performance criteria, statistical manipulation of results submitted by 13 laboratories, (6 withdrew) allowed an estimate to be made of the true value of the analyte content. The Nalimov test was used for detection of outlying results. The Cochran and Bartlett tests were employed for testing the homogeneity of variances. The normality of results distribution was tested according to the Kolmogorov-Smirnov-Lilliefors test. One-way analysis of variance (ANOVA) was employed to calculate the within and between-laboratory standard deviations, the overall mean and confidence interval for the CTC and epi-CTC content of each of the RMs. Certified values were within or very close to the target concentration ranges specified in the SMT contract. These studies have demonstrated the successful production and certification of CTC-containing and CTC-free porcine RMs.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 1. Hematological and population level assessment.

PubMed

Lohner, T W; Reash, R J; Willet, V E; Rose, L A

2001-11-01

Sunfish were collected from coal ash effluent-receiving streams and Ohio River watershed reference sites to assess the effects of exposure to low-level selenium concentrations. Selenium, copper, and arsenic concentrations were statistically higher in tissue samples from exposed fish than in reference fish. Leukopenia, lymphocytosis, and neutropenia were evident in exposed fish and were indicative of metal exposure and effect. White blood cell counts and percent lymphocyte values were significantly correlated with liver selenium concentrations. Plasma protein levels were significantly lower in exposed fish than in fish from the Ohio River, indicating that exposed fish may have been nutritionally stressed. Condition factors for fish from the ash pond-receiving streams were the same as, or lower than, those of fish from the reference sites. There was no evidence that the growth rate of fish in the receiving streams differed from that of fish in the reference streams. Despite liver selenium concentrations which exceeded reported toxicity thresholds and evidence of significant hematological changes, there were no significant differences in fish condition factors, liver-somatic indices, or length-weight regressions related to selenium.

Reference intervals for putative biomarkers of drug-induced liver injury and liver regeneration in healthy human volunteers.

PubMed

Francis, Ben; Clarke, Joanna I; Walker, Lauren E; Brillant, Nathalie; Jorgensen, Andrea L; Park, B Kevin; Pirmohamed, Munir; Antoine, Daniel J

2018-05-02

The potential of mechanistic biomarkers to improve the prediction of drug-induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration as well as to characterize their natural variability and impact of diurnal variation. Serum samples from 200 healthy volunteers were recruited as part of a cross sectional study; of these, 50 subjects had weekly serial sampling over 3 weeks, while 24 had intensive blood sampling over a 24h period. Alanine aminotransferase (ALT), MicroRNA-122 (miR-122), high mobility group box-1 (HMGB1), total keratin-18 (FL-K18), caspase cleaved keratin-18 (cc-K18), glutamate dehydrogenase (GLDH) and colony stimulating factor-1 (CSF-1) were assessed by validated assays. Reference intervals were established for each biomarker based on the 97.5% quantile (90% CI) following the assessment of fixed effects in univariate and multivariable models (ALT 50 (41-50) U/l, miR-122 3548 (2912-4321) copies/µl, HMGB1 2.3 (2.2-2.4) ng/ml, FL-K18 475 (456-488) U/l, cc-K18 272 (256-291) U/l, GLDH 27 (26-30) U/l and CSF-1 2.4 (2.3-2.9) ng/ml). There was a small but significant intra-individual time random effect detected but no significant impact of diurnal variation was observed, with the exception of GLDH. Reference intervals for novel DILI biomarkers have been described for the first time. An upper limit of a reference range might represent the most appropriate method to utilize these data. Regulatory authorities have published letters of support encouraging further qualification of leading candidate biomarkers. These data can now be used to interpret data from exploratory clinical DILI studies and to assist their further qualification. Drug-induced liver injury (DILI) has a big impact on patient health and the development of new medicines. Unfortunately, currently used blood-based tests to assess liver injury and recovery suffer from insufficiencies. Newer blood-based tests (biomarkers) have been described that accurately predict the onset and recovery from DILI. Here, in this study we describe reference intervals from investigations designed, for the first time, with the intension to assess the natural variation of these newer biomarkers in healthy volunteers. The outcomes of these results can be used to aid the interpretation of data from patients with suspected liver toxicity. Copyright © 2018. Published by Elsevier B.V.

Systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection based on Laennec's capsule: proposal of a novel comprehensive surgical anatomy of the liver.

PubMed

Sugioka, Atsushi; Kato, Yutaro; Tanahashi, Yoshinao

2017-01-01

Anatomical liver resection with the Glissonean pedicle isolation is widely approved as an essential procedure for safety and curability. Especially, the extrahepatic Glissonean pedicle isolation without parenchymal destruction should be an ideal procedure. However, the surgical technique has not been standardized due to a lack of anatomical understanding. Herein, we proposed a novel comprehensive surgical anatomy of the liver based on Laennec's capsule that would give a theoretical background to the extrahepatic Glissonean pedicle isolation. Laennec's capsule is the proper membrane that covers not only the entire surface of the liver including the bare area but also the intrahepatic parenchyma surrounding the Glissonean pedicles. Consequently, there exists a gap between the Glissonean pedicle and Laennec's capsule that could be reached extrahepatically and allows us to isolate the extrahepatic Glissonean pedicle without parenchymal destruction systematically. For standardization, it is essential to approach the "six gates" indicated by the "four anatomical landmarks": the Arantius plate, the umbilical plate, the cystic plate and the Glissonean pedicle of the caudate process (G1c). This novel anatomy would contribute to standardize the surgical techniques of the systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection including laparoscopic or robotic liver resection and to bring innovative changes in hepatobiliary surgery for spreading safe and curable liver resection. © 2017 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

PubMed

Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

2015-06-01

Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Quantification of Liver Fat in the Presence of Iron Overload

PubMed Central

Horng, Debra E.; Hernando, Diego; Reeder, Scott B.

2017-01-01

Purpose To evaluate the accuracy of R2* models (1/T2* = R2*) for chemical shift-encoded magnetic resonance imaging (CSE-MRI)-based proton density fat-fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard. Materials and Methods Two Monte Carlo simulations were implemented to compare the root-mean-squared-error (RMSE) performance of single-R2* and dual-R2* correction in a theoretical liver environment with high iron. Fatty liver was defined as hepatic PDFF >5.6% based on MRS; only subjects with fatty liver were considered for analyses involving fat. From a group of 40 patients with known/suspected iron overload, nine patients were identified at 1.5T, and 13 at 3.0T with fatty liver. MRS linewidth measurements were used to estimate R2* values for water and fat peaks. PDFF was measured from CSE-MRI data using single-R2* and dual-R2* correction with magnitude and complex fitting. Results Spectroscopy-based R2* analysis demonstrated that the R2* of water and fat remain close in value, both increasing as iron overload increases: linear regression between R2*W and R2*F resulted in slope = 0.95 [0.79–1.12] (95% limits of agreement) at 1.5T and slope = 0.76 [0.49–1.03] at 3.0T. MRI-PDFF using dual-R2* correction had severe artifacts. MRI-PDFF using single-R2* correction had good agreement with MRS-PDFF: Bland–Altman analysis resulted in −0.7% (bias) ± 2.9% (95% limits of agreement) for magnitude-fit and −1.3% ± 4.3% for complex-fit at 1.5T, and −1.5% ± 8.4% for magnitude-fit and −2.2% ± 9.6% for complex-fit at 3.0T. Conclusion Single-R2* modeling enables accurate PDFF quantification, even in patients with iron overload. PMID:27405703

Association of inorganic arsenic exposure with liver cancer mortality: A meta-analysis.

PubMed

Wang, Weijing; Cheng, Shuo; Zhang, Dongfeng

2014-11-01

The association of long-term inorganic arsenic (iAs) exposure through drinking water with risk of liver cancer mortality remains controversial. Therefore, we reviewed and quantitatively summarized the evidence from observational studies with a meta-analysis. Pertinent studies were identified by searching PubMed and China National Knowledge Infrastructure through May 2014 and by reviewing the reference lists of retrieved articles. Studies that reported standardized mortality ratios (SMRs) with 95% confidence interval (95% CIs) for the association of iAs in drinking water with liver cancer were eligible. The random effect model was adopted as the pooling method to generate summary effect estimates (meta-SMRs). Of the 4851 articles identified through searching databases, 7 articles including 12 studies were included in the meta-analysis. The meta-SMR with 95% CI of liver cancer for the highest versus lowest category of iAs exposure level in drinking water was 1.80 (1.61 to 2.02). Furthermore, an increased risk of liver cancer mortality was found in both females [1.80 (1.45 to 2.24)] and males [1.84 (1.56 to 2.16)]. In subgroup analysis, the meta-SMRs were 1.93 (1.72 to 2.15) for cohort studies, 1.60 (1.22 to 2.10) for ecological studies, 1.93 (1.72 to 2.15) for studies conducted in Asia, and 1.60 (1.22 to 2.10) for studies conducted in South America, respectively. After removing the 3 studies conducted by Smith et al. (having two studies separately for males and females) and Chen et al. that had a strong effect on heterogeneity, a significant association was also found [1.85 (1.72 to 1.99)]. This meta-analysis indicates that long-term iAs exposure through drinking water increases the risk of liver cancer mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantitative MR Imaging of Hepatic Steatosis: Validation in Ex Vivo Human Livers

PubMed Central

Bannas, Peter; Kramer, Harald; Hernando, Diego; Agni, Rashmi; Cunningham, Ashley M.; Mandal, Rakesh; Motosugi, Utaroh; Sharma, Samir D.; del Rio, Alejandro Munoz; Fernandez, Luis; Reeder, Scott B.

2015-01-01

Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the “proton density fat-fraction” (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5T in 13 explanted human livers. We performed co-localized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117), tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction and histology. Intra-observer agreement, inter-observer agreement and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984; CI: 0.978–0.989) and strong correlation with histology (r=0.850; CI: 0.791–0.894) and triglyceride extraction (r=0.871; CI: 0.818–0.909). Intra-observer agreement, inter-observer agreement and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all p<0.001). Conclusion MRI-PDFF is an accurate, precise and reader-independent non-invasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver. PMID:26224591

Demystifying liver iron concentration measurements with MRI.

PubMed

Henninger, B

2018-06-01

This Editorial comment refers to the article: Non-invasive measurement of liver iron concentration using 3-Tesla magnetic resonance imaging: validation against biopsy. D'Assignies G, et al. Eur Radiol Nov 2017. • MRI is a widely accepted reliable tool to determine liver iron concentration. • MRI cannot measure iron directly, it needs calibration. • Calibration curves for 3.0T are rare in the literature. • The study by d'Assignies et al. provides valuable information on this topic. • Evaluation of liver iron overload should no longer be restricted to experts.

Mortality among British Columbians testing for hepatitis C antibody.

PubMed

Yu, Amanda; Spinelli, John J; Cook, Darrel A; Buxton, Jane A; Krajden, Mel

2013-04-02

Hepatitis C virus (HCV) infection is a major preventable and treatable cause of morbidity and mortality. The ability to link population based centralized laboratory HCV testing data with administrative databases provided a unique opportunity to compare mortality between HCV seronegative and seropositive individuals. Through the use of laboratory testing patterns and results, the objective of this study was to differentiate the viral effects of mortality due to HCV infection from risk behaviours/activities that are associated with acquisition of HCV infection. Serological testing data from the British Columbia (BC) Centre for Disease Control Public Health Microbiology and Reference Laboratory from 1992-2004 were linked to the BC Vital Statistics Agency death registry. Four groups of HCV testers were defined by their HCV antibody (anti-HCV) testing patterns: single non-reactive (SNR); serial multiple tested non-reactive (MNR); reactive at initial testing (REAC); and seroconverter (SERO) (previously seronegative followed by reactive, a marker for incident infection). Standardized mortality ratios (SMRs) were calculated to compare the relative risk of all cause and disease specific mortality to that of the BC population for each serological group. Time dependent Cox proportional hazard regression was used to compare hazard ratios (HRs) among HCV serological groups. All anti-HCV testers had higher SMRs than the BC population. Referent to the SNR group, the REAC group had higher risks for liver (HR: 9.62; 95% CI=8.55-10.87) and drug related mortality (HR: 13.70; 95% CI=11.76-16.13). Compared to the REAC group, the SERO group had a lower risk for liver (HR: 0.53; 95% CI=0.24-0.99), but a higher risk for drug related mortality (HR: 1.54; 95% CI=1.12-2.05). These findings confirm that individuals who test anti-HCV positive have increased mortality related to progressive liver disease, and that a substantial proportion of the mortality is attributable to drug use and risk behaviours/activities associated with HCV acquisition. Mortality reduction in HCV infected individuals will require comprehensive prevention programming to reduce the harms due to behaviours/activities which relate to HCV acquisition, as well as HCV treatment to prevent progression of chronic liver disease.

Systematic review of severe acute liver injury caused by terbinafine.

PubMed

Yan, Jun; Wang, Xiaolin; Chen, Shengli

2014-08-01

Terbinafine is an effective antimicrobial agent against dermatophytes, cryptococcus and other fungi. It is the preferred drug to treat onychomycosis. However, severe acute hepatitis from oral terbinafine administration has been recently reported. To describe a representative case, and review the literature regarding the best evidence on treatment and prognosis of severe acute hepatitis caused by oral terbinafine. The literature was searched for publications on severe hepatitis caused by terbinafine using MEDLINE, China Biology Medicine Disc, and the VIP Medical Information Resource System. Related references were searched manually. Seventeen English and three Chinese references of case reports were included after eliminating duplicate publications. No randomized control studies were found. Liver enzyme levels were found to have been increased significantly. Abdominal ultrasound demonstrated cholestasis. Severe acute liver injury is a known, but unusual complication of terbinafine exposure. The prognosis is often good with appropriate treatment. Liver function assessment before treatment and periodic monitoring 4-6 weeks after initiation of treatment is recommended.

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

NASA Astrophysics Data System (ADS)

Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid

2018-01-01

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest achievable mean liver BED. The results indicate that spatiotemporal treatments can achieve substantial reductions in normal tissue dose and BED, and that local optimization techniques provide high-quality plans that are close to realizing the maximum potential normal tissue dose reduction.

Liver regeneration in donors and adult recipients after living donor liver transplantation.

PubMed

Haga, Junko; Shimazu, Motohide; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Fuchimoto, Yasushi; Hoshino, Ken; Morikawa, Yasuhide; Kitajima, Masaki; Kitagawa, Yuko

2008-12-01

In living donor liver transplantation, the safety of the donor operation is the highest priority. The introduction of the right lobe graft was late because of concerns about donor safety. We investigated donor liver regeneration by the types of resected segments as well as recipients to assess that appropriate regeneration was occurring. Eighty-seven donors were classified into 3 groups: left lateral section donors, left lobe donors, and right lobe donors. Forty-seven adult recipients were classified as either left or right lobe grafted recipients. Volumetry was retrospectively performed at 1 week, 1, 2, 3, and 6 months, and 1 year after the operation. In the right lobe donor group, the remnant liver volume was 45.4%, and it rapidly increased to 68.9% at 1 month and 89.8% at 6 months. At 6 months, the regeneration ratios were almost the same in all donor groups. The recipient liver volume increased rapidly until 2 months, exceeding the standard liver volume, and then gradually decreased to 90% of the standard liver volume. Livers of the right lobe donor group regenerated fastest in the donor groups, and the recipient liver regenerated faster than the donor liver. Analyzing liver regeneration many times with a large number of donors enabled us to understand the normal liver regeneration pattern. Although the donor livers did not reach their initial volume, the donors showed normal liver function at 1 year. The donors have returned to their normal daily activities. Donor hepatectomy, even right hepatectomy, can be safely performed with accurate preoperative volumetry and careful decision-making concerning graft-type selection.

[Investigation of potential toxic factors for fleece-flower root： from perspective of processing methods evolution].

PubMed

Cui, He-Rong; Bai, Zhao-Fang; Song, Hai-Bo; Jia, Tian-Zhu; Wang, Jia-Bo; Xiao, Xiao-He

2016-01-01

In recent years, the rapid growth of reports on fleece-flower root-caused liver damages has drawn wide attention of both at home and abroad, however, there were rare literature on toxicology of fleece-flower root in ancient Chinese medicine. But why there are so many reports on toxicology of fleece-flower root now compared with the ancient literature? As a typical tonic medicine, the clinical utility of fleece-flower root was largely limited by its standardization and reliability of processing methods in ancient Chinese medicine. The ancient processing methods of fleece-flower root emphasized nine times of steaming and nine times of drying, while the modern processes have been simplified into one time of steaming. Whether the differences between ancient and modern processing methods are the potential cause of the increased events of fleece-flower root-caused liver damages. We will make deep analysis and provide new clues and perspectives for the research on its toxicity. This article, therefore, would discuss the affecting factors and key problems in toxicity attenuation of fleece-flower root on the basis of sorting out the processing methods of fleece-flower root in ancient medical books and modern standards, in order to provide the reference for establishing specification for toxicity attenuation of fleece-flower root. Copyright© by the Chinese Pharmaceutical Association.

Pediatric-specific reference intervals in a nationally representative sample of Iranian children and adolescents: the CASPIAN-III study.

PubMed

Kelishadi, Roya; Marateb, Hamid Reza; Mansourian, Marjan; Ardalan, Gelayol; Heshmat, Ramin; Adeli, Khosrow

2016-08-01

This study aimed to determine for the first time the age- and gender-specific reference intervals for biomarkers of bone, metabolism, nutrition, and obesity in a nationally representative sample of the Iranian children and adolescents. We assessed the data of blood samples obtained from healthy Iranian children and adolescents, aged 7 to 19 years. The reference intervals of glucose, lipid profile, liver enzymes, zinc, copper, chromium, magnesium, and 25-hydroxy vitamin D [25(OH)D] were determined according to the Clinical & Laboratory Standards Institute C28-A3 guidelines. The reference intervals were partitioned using the Harris-Boyd method according to age and gender. The study population consisted of 4800 school students (50% boys, mean age of 13.8 years). Twelve chemistry analyses were partitioned by age and gender, displaying the range of results between the 2.5th to 97.5th percentiles. Significant differences existed only between boys and girls at 18 to 19 years of age for low density lipoprotein-cholesterol. 25(OH)D had the only reference interval that was similar to all age groups and both sexes. This study presented the first national database of reference intervals for a number of biochemical markers in Iranian children and adolescents. It is the first report of its kind from the Middle East and North Africa. The findings underscore the importance of providing reference intervals in different ethnicities and in various regions.

Choline and Fructooligosaccharide: Non-alcoholic Fatty Liver Disease, Cardiac Fat Deposition, and Oxidative Stress Markers

PubMed Central

Borges Haubert, Nadia Juliana Beraldo Goulart; Marchini, Julio Sergio; Carvalho Cunha, Selma Freire; Suen, Vivian Marques Miguel; Padovan, Gilberto Joao; Jordao, Alceu Afonso; Marchini Alves, Claudia Maria Meirelles; Marchini, Julio Flavio Meirelles; Vannucchi, Helio

2015-01-01

This study investigates the treatment of non-alcoholic fatty liver disease (NAFLD) in rats with choline and fructooligosaccharide (FOS). The healthy control group received standard diet. The other three groups consisted of animals with NAFLD. Group Estr received standard diet; group Echo received standard diet plus choline (3 g/100 g diet); and group Efos received standard diet plus FOS (10 g/100 g diet). Food intake, weight, urinary nitrogen, urinary ammonia, total cholesterol, serum triacylglyceride, liver and heart weights, tissue nitrogen, tissue fat, vitamin E, TBARS, and reduced glutathione (GSH) were measured in hepatic and heart tissue. Choline and FOS treatments resulted in total mean fat reduction in liver and heart tissue of 0.2 and 1.7 g, respectively. Both treatments were equally effective in reducing hepatic and cardiac steatosis. There were no differences in the TBARS level among experimental and control groups, indicating that the proposed treatments had no added protection against free radicals. While all experimental groups had increased vitamin E and GSH levels, choline treatment led to a significant increase compared to control. PMID:25987847

Polycyclic aromatic hydrocarbons, aliphatic hydrocarbons, trace elements and monooxygenase activity in birds nesting on the North Platte River, Casper, Wyoming, USA

USGS Publications Warehouse

Custer, T.W.; Custer, Christine M.; Dickerson, K.; Allen, K.; Melancon, M.J.; Schmidt, L.J.

2001-01-01

Tree swallow (Tachycineta bicolor) and house wren (Troglodytes aedon) eggs and chicks were collected near a refinery site on the North Platte River, Casper, Wyoming, USA and at a reference site 10 km upstream. Total polycylic aromatic hydrocarbon (PAH) concentrations in swallow and wren chicks were higher at the refinery site than at the reference site. Polycylic aromatic hydrocarbon concentrations in sediment and chick dietary samples were consistent with these findings. The general lack of methylated PAHs in sediment, diet, and bird carcasses suggested that the PAHs were derived from combustion and not from petroleum. The predominance of odd numbered aliphatic hydrocarbons and the low ratios (≤ 0.25) of pristane: n-C17 and phytane: n-C18 in chick and diet samples also suggested that swallow and wren chicks were not being chronically exposed to petroleum. Mean ethoxyresorufin-O-dealkylase and benzyloxyresorufin-O-dealkylase activities in tree swallow livers averaged nine times higher at the refinery site than at the reference site and were probably induced by exposure to PAHs. Trace element concentrations in eggs and livers of swallows and wrens were similar or greater at the reference site than at the refinery site. Selenium, strontium, and boron concentrations were elevated in eggs and livers of swallows and wrens at both the refinery and reference sites.

Novel α-Oxoamide Advanced-Glycation Endproducts within the N6-Carboxymethyl Lysine and N6-Carboxyethyl Lysine Reaction Cascades.

PubMed

Baldensperger, Tim; Jost, Tobias; Zipprich, Alexander; Glomb, Marcus A

2018-02-28

The highly reactive α-dicarbonyl compounds glyoxal and methylglyoxal are major precursors of posttranslational protein modifications in vivo. Model incubations of N 2 -t-Boc-lysine and either glyoxal or methylglyoxal were used to further elucidate the underlying mechanisms of the N 6 -carboxymethyl lysine and N 6 -carboxyethyl lysine reaction cascades. After independent synthesis of the authentic reference standards, we were able to detect N 6 -glyoxylyl lysine and N 6 -pyruvoyl lysine for the first time by HPLC-MS 2 analyses. These two novel amide advanced-glycation endproducts were exclusively formed under aerated conditions, suggesting that they were potent markers for oxidative stress. Analogous to the well-known Strecker degradation pathway, leading from amino acids to Strecker acids, the oxidation of an enaminol intermediate is suggested to be the key mechanistic step. A highly sensitive workup for the determination of AGEs in tissues was developed. In support of our hypothesis, the levels of N 6 -glyoxylyl lysine and N 6 -pyruvoyl lysine in rat livers indeed correlated with liver cirrhosis and aging.

Standard value of ultrasound elastography using acoustic radiation force impulse imaging (ARFI) in healthy liver tissue of children and adolescents.

PubMed

Eiler, J; Kleinholdermann, U; Albers, D; Dahms, J; Hermann, F; Behrens, C; Luedemann, M; Klingmueller, V; Alzen, G F P

2012-10-01

Ultrasound elastography by acoustic radiation force impulse imaging (ARFI) is used in adults for non invasive measurement of liver stiffness, indicating liver diseases like fibrosis. To establish ARFI in children and adolescents we determined standard values of healthy liver tissue and analysed potentially influencing factors. 132 patients between 0 and 17 years old were measured using ARFI. None of them had any liver disease or any other disease that could affect the liver secondarily. All patients had a normal ultrasound scan, a normal BMI and normal liver function tests. The mean value of all ARFI measurements was calculated and potentially influencing factors were analysed. The mean value of all ARFI elastography measurements was 1.16 m/sec (SD ± 0.14 m/sec). Neither age (p = 0.533) nor depth of measurement (p = 0.066) had no significant influence on ARFI values, whereas a significant effect of gender was found with lower ARFI values in females (p = 0.025), however, there was no significant interaction between age groups (before or after puberty) and gender (p = 0.276). There was an interlobar difference with lower values in the right liver lobe compared to the left (p = 0.036) and with a significantly lower variance (p < 0.001). Consistend values were measured by different examiners (p = 0.108), however, the inter examiner variance deviated significantly (p < 0.001). ARFI elastography is a reliable method to measure liver stiffness in children and adolescents. In relation to studies which analyse liver diseases, the standard value of 1.16 m/sec (± 0.14 m/sec) allows a differentiation of healthy versus pathological liver tissue. © Georg Thieme Verlag KG Stuttgart · New York.

Guidelines on the management of abnormal liver blood tests

PubMed Central

Cramb, Rob; Davison, Suzanne M; Dillon, John F; Foulerton, Mark; Godfrey, Edmund M; Hall, Richard; Harrower, Ulrike; Hudson, Mark; Langford, Andrew; Mackie, Anne; Mitchell-Thain, Robert; Sennett, Karen; Sheron, Nicholas C; Verne, Julia; Walmsley, Martine; Yeoman, Andrew

2018-01-01

These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease. PMID:29122851

Diffusion-Weighted PROPELLER MRI for Quantitative Assessment of Liver Tumor Necrotic Fraction and Viable Tumor Volume in VX2 Rabbits

PubMed Central

Deng, Jie; Virmani, Sumeet; Young, Joseph; Harris, Kathleen; Yang, Guang-Yu; Rademaker, Alfred; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

2010-01-01

Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI provides more accurate liver tumor necrotic fraction (NF) and viable tumor volume (VTV) measurements than conventional DW-SE-EPI (spin echo echo-planar imaging) methods. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 10 VX2 liver tumors, DW-PROPELLER and DW-SE-EPI scans were performed at contiguous axial slice positions covering each tumor volume. Apparent diffusion coefficient maps of each tumor were used to generate spatially resolved tumor viability maps for NF and VTV measurements. We compared NF, whole tumor volume (WTV), and VTV measurements to corresponding reference standard histological measurements based on correlation and concordance coefficients and the Bland–Altman analysis. Results DW-PROPELLER generally improved image quality with less distortion compared to DW-SE-EPI. DW-PROPELLER NF, WTV, and VTV measurements were strongly correlated and satisfactorily concordant with histological measurements. DW-SE-EPI NF measurements were weakly correlated and poorly concordant with histological measurements. Bland–Altman analysis demonstrated that DWPROPELLER WTV and VTV measurements were less biased from histological measurements than the corresponding DW-SE-EPI measurements. Conclusion DW-PROPELLER MRI can provide spatially resolved liver tumor viability maps for accurate NF and VTV measurements, superior to DW-SE-EPI approaches. DWPROPELLER measurements may serve as a noninvasive surrogate for pathology, offering the potential for more accurate assessments of therapy response than conventional anatomic size measurements. PMID:18407540

Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.

PubMed

Lv, F; Tang, J; Luo, Y; Li, Z; Meng, X; Zhu, Z; Li, T

2011-10-01

The aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) imaging of active bleeding from hepatic and splenic trauma. Three hundred and ninety-two patients with liver or/and spleen trauma (179 liver and 217 spleen injuries), who underwent CEUS examinations following contrast-enhanced computed tomography (CT), were enrolled in this retrospective study over a period of >4 years. CEUS detected contrast medium extravasation or pooling in 16% (63/396) of liver or spleen lesions in 61 patients, which was confirmed by contrast-enhanced CT. Special attention was paid to observing the presence, location, and characteristics of the extravasated or pooled contrast medium. The CEUS detection rate for active bleeding was not different from that of contrast-enhanced CT (p=0.333). Information from surgery, minimally invasive treatment and conservative treatment was used as reference standard, and the sensitivities of the two techniques were not different (p=0.122). Of 63 lesions in 61 patients, CEUS showed that 74.6% (47/63) (21 liver lesions and 26 spleen lesions) presented contrast medium extravasation or pooling, both in the organ and out the capsule, in 14.3% (9/63) and only outside the capsule in 11.1% (7/63). CEUS imaging of active bleeding from hepatic and splenic trauma presented various characteristics, and the sizes and shapes of the active bleeding due to contrast medium extravasation or pooling were variable. CEUS can show the active bleeding associated with hepatic and splenic trauma with various imaging characteristics, thus making it possible to diagnose active bleeding using CEUS.

Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney

PubMed Central

2010-01-01

Background Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups). Results The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group. Conclusions It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina. PMID:20353607

Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney.

PubMed

Ponce-Canchihuamán, Johny C; Pérez-Méndez, Oscar; Hernández-Muñoz, Rolando; Torres-Durán, Patricia V; Juárez-Oropeza, Marco A

2010-03-31

Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups). The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group. It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina.

Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage.

PubMed

Piscaglia, F; Salvatore, V; Mulazzani, L; Cantisani, V; Schiavone, C

2016-02-01

In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(®), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4 cm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8 cm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(®) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(®) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2 - 3 cm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1 - 2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(®), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(®) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i. e., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5 Hz and in larger regions; thus this technique is also termed real-time 2 D SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(®) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. · The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e. g. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2 - 3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. · Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. · Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan®, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. · Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED) © Georg Thieme Verlag KG Stuttgart · New York.

[Preliminary study on effective components of Tripterygium wilfordii for liver toxicity based on spectrum-effect correlation analysis].

PubMed

Zhao, Xiao-Mei; Pu, Shi-Biao; Zhao, Qing-Guo; Gong, Man; Wang, Jia-Bo; Ma, Zhi-Jie; Xiao, Xiao-He; Zhao, Kui-Jun

2016-08-01

In this paper, the spectrum-effect correlation analysis method was used to explore the main effective components of Tripterygium wilfordii for liver toxicity, and provide reference for promoting the quality control of T. wilfordii. Chinese medicine T.wilfordii was taken as the study object, and LC-Q-TOF-MS was used to characterize the chemical components in T. wilfordii samples from different areas, and their main components were initially identified after referring to the literature. With the normal human hepatocytes (LO2 cell line)as the carrier, acetaminophen as positive medicine, and cell inhibition rate as testing index, the simple correlation analysis and multivariate linear correlation analysis methods were used to screen the main components of T. wilfordii for liver toxicity. As a result, 10 kinds of main components were identified, and the spectrum-effect correlation analysis showed that triptolide may be the toxic component, which was consistent with previous results of traditional literature. Meanwhile it was found that tripterine and demethylzeylasteral may greatly contribute to liver toxicity in multivariate linear correlation analysis. T. wilfordii samples of different varieties or different origins showed large difference in quality, and the T. wilfordii from southwest China showed lower liver toxicity, while those from Hunan and Anhui province showed higher liver toxicity. This study will provide data support for further rational use of T. wilfordii and research on its liver toxicity ingredients. Copyright© by the Chinese Pharmaceutical Association.

Hepatoprotective effects of Micromeria croatica ethanolic extract against CCl4-induced liver injury in mice.

PubMed

Vladimir-Knežević, Sanda; Cvijanović, Olga; Blažeković, Biljana; Kindl, Marija; Štefan, Maja Bival; Domitrović, Robert

2015-07-15

Micromeria croatica (Pers.) Schott is an aromatic plant from Lamiaceae family previously found to possess potent in vitro antioxidant activity which is mainly attributed to the high level of polyphenolic substances. The aim of this study was to investigate the hepatoprotective activity and possible underlying mechanisms of Micromeria croatica ethanolic extract (MC) using a model of carbon tetrachloride (CCl4)-induced liver injury in mice. Male BALB/cN mice were randomly divided into seven groups: control group received saline, MC group received ethanolic extract of M. croatica in 5% DMSO (100 mg/kg b.w., p.o.), and CCl4 group was administered CCl4 dissolved in corn oil (2 mL/kg, 10% v/v, ip). MC50, MC200 and MC400 groups were treated with MC orally at doses of 50, 200 and 400 mg/kg once daily for 2 consecutive days, respectively, 6 h after CCl4 intoxication. The reference group received silymarin at dose of 400 mg/kg. At the end of experiment, blood and liver samples were collected for biochemical, histopathological, immunohistochemical and Western blot analyses. In addition, major phenolic compounds in MC were quantified by HPLC-DAD. CCl4 intoxication resulted in liver cells damage and oxidative stress and triggered inflammatory response in mice livers. MC treatment decreased ALT activity and prevented liver necrosis. Improved hepatic antioxidant status was evident by increased Cu/Zn SOD activity and decreased 4-hydroxynonenal (4-HNE) formation in the livers. Concomitantly, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were overexpressed. The hepatoprotective activity of MC was accompanied by the increase in nuclear factor-kappaB (NF-κB) activation and tumor necrosis factor-alpha (TNF-α) expression, indicating amelioration of hepatic inflammation. Additionally, MC prevented tumor growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression, suggesting the potential for suppression of hepatic fibrogenesis. These results of the present study demonstrated that MC possesses in vivo antioxidant and anti-inflammatory activity and exhibits antifibrotic potential, which are comparable to those of standard hepatoprotective compound silymarin.

Reproducibility of shear wave elastography (SWE) in patients with chronic liver disease

PubMed Central

Salomone Megna, Angelo; Ragucci, Monica; De Luca, Massimo; Marino Marsilia, Giuseppina; Nardone, Gerardo; Coccoli, Pietro; Prinster, Anna; Mannelli, Lorenzo; Vergara, Emilia; Monti, Serena; Liuzzi, Raffaele; Incoronato, Mariarosaria

2017-01-01

The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14–16.7 kPa and were 4.49 kPa and 2.92–7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87–0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity. PMID:29023554

Influence of gut microbiota and intestinal barrier on enterogenic infection after liver transplantation.

PubMed

Mu, Jingzhou; Chen, Qiuyu; Zhu, Liang; Wu, Yunhong; Liu, Suping; Zhao, Yufei; Ma, Tonghui

2018-04-27

Liver transplantation is currently a standard therapy for patients with end-stage liver diseases and hepatocellular carcinoma. Given that liver transplantation has undergone a thriving development in these decades, the survival rates after liver transplantation have markedly improved as a result of the critical advancement in surgical techniques, immunosuppressive therapies, and postoperative care. However, infection remains a fatal complication after liver transplantation surgery. In particular, enterogenic infection represents a major complication in liver transplant recipients. This article gives an overview of infection cases after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factor, outcome, and treatment.

Correlation between acoustic radiation force impulse (ARFI)-based tissue elasticity measurements and perfusion parameters acquired by perfusion CT in cirrhotic livers: a proof of principle.

PubMed

Esser, Michael; Bitzer, Michael; Kolb, Manuel; Fritz, Jan; Kurucay, Mustafa; Ruff, Christer; Horger, Marius

2018-06-13

To investigate whether liver stiffness measured by acoustic radiation force impulse (ARFI) sonoelastography always correlates with the liver perfusion parameters quantified by perfusion CT in patients with known liver cirrhosis. Sonoelastography and perfusion CT were performed in 50 patients (mean age 65.5; range 45-87 years) with liver cirrhosis, who were classified according to Child-Pugh into class A (30/50, 60%), B (17/50, 34%), and C (3/50, 6%). For standardized ARFI measurements in the left liver lobe at a depth of 4 cm, a convex 6-MHz probe was used. CT examinations were performed using 80 kV, 100 mAs, and 50 ml of iodinated contrast agent injected at 5 ml/s. Using standardized region-of-interest measurements, we quantified arterial, portal venous, and total liver perfusion. There was a significant linear correlation between tissue stiffness and arterial liver perfusion (p = 0.015), and also when limiting the analysis to patients with histology (p = 0.019). In addition, there was a positive correlation between the total blood supply (arterial + portal-venous liver perfusion) to the liver and tissue stiffness (p = 0.001; with histology, p = 0.027). Shear wave velocity increased with higher Child-Pugh stages (p = 0.013). The degree of tissue stiffness in cirrhotic livers correlates expectedly-even if only moderately-with the magnitude of arterial liver perfusion and total liver perfusion. As such, liver elastography remains the leading imaging tool in assessing liver fibrosis.

Diagnostic performance of transient elastography for detection of methotrexate-induced liver injury using Roenigk classification in Asian patients with psoriasis: a retrospective study.

PubMed

Rongngern, Pasinee; Chularojanamontri, Leena; Wongpraparut, Chanisada; Silpa-Archa, Narumol; Chotiyaputta, Watcharasak; Pongpaibul, Ananya; Charatcharoenwitthaya, Phunchai

2017-07-01

Liver biopsy, the gold standard for monitoring methotrexate-induced liver fibrosis in psoriasis patients, has potential morbidity and mortality. Transient elastography (TE) has been widely used as an alternative non-invasive method. Currently, psoriasis-specific data of TE comparing to Roenigk histopathology is lacking. This retrospective study assessed the diagnostic performance of TE in the detection of methotrexate-induced liver injury and liver fibrosis in Asian psoriasis patients. Risk factors that associated with liver injury by TE and histopathology were also determined. Psoriasis patients who had received methotrexate and undergone both TE and liver biopsy (gold standard) examinations between 2005 and 2016 were enrolled. Ten of 41 patients developed methotrexate-induced liver injury (Roenigk grade ≥3a) and two of them had significant liver fibrosis (Metavir fibrosis stage ≥2). Area under the receiver operating characteristic curve (AUROC = 0.78) indicated that TE was capable of identifying patients with and without liver injury. Using a cut-off TE value of 7.1 kilopascal (kPa), this ultrasound-based elastography yielded 50% sensitivity and 83.9% specificity for detecting methotrexate-induced liver injury and had 50% sensitivity and 76.9% specificity for identifying significant liver fibrosis. A total cumulative dosage of methotrexate, age, gender, metabolic syndrome, and metabolic components were not significantly associated with TE values ≥7.1 kPa and Roenigk grade ≥3a. Thus, using clinical context, laboratory information, and a cut-off TE value of 7.1, TE is an attractable non-invasive tool for identify psoriasis patients who have a low probability of methotrexate-induced liver injury and significant liver fibrosis. Liver biopsy can be reserved for selected patients.

Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition.

PubMed

Lykke, Mikkel; Hother, Anne-Louise; Hansen, Christian F; Friis, Henrik; Mølgaard, Christian; Michaelsen, Kim F; Briend, André; Larsen, Torben; Sangild, Per T; Thymann, Thomas

2013-01-01

Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P < 0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P < 0.001), digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P < 0.001), and the liver had a vacuolated appearance and tendency toward increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition.

Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition

PubMed Central

Lykke, Mikkel; Hother, Anne-Louise; Hansen, Christian F; Friis, Henrik; Mølgaard, Christian; Michaelsen, Kim F; Briend, André; Larsen, Torben; Sangild, Per T; Thymann, Thomas

2013-01-01

Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P < 0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P < 0.001), digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P < 0.001), and the liver had a vacuolated appearance and tendency toward increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition. PMID:23977413

Pinworm infection masquerading as colorectal liver metastasis.

PubMed

Roberts, K J; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

2012-09-01

Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E. vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur.

Pinworm infection masquerading as colorectal liver metastasis

PubMed Central

Roberts, KJ; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

2012-01-01

Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur. PMID:22943320

From the bottom of the heart: Measuring liver iron concentration on cardiac MRI.

PubMed

Tan, Stephanie; Peng, Qi; Liszewski, Mark C; Taragin, Benjamin H

Patients with hemochromatosis require regular surveillance of liver and cardiac iron concentration with liver and cardiac MRI. However, cardiac MRI includes a part of the liver in the field of view. The purpose of this retrospective and prospective study is to determine if liver T2* measured on cardiac MRI may be used as a surrogate for T2* obtained on standard liver MRI. Liver iron concentrations were measured on cardiac and liver MRI in 21 patients. Although statistically significant, the difference may be clinically insignificant as the same patients merited chelation therapy when relying on either the cardiac or liver MRI. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis of the 3-sulfates of S-acyl glutathione conjugated bile acids and their biotransformation by a rat liver cytosolic fraction.

PubMed

Mitamura, Kuniko; Hori, Naohiro; Mino, Shiori; Iida, Takashi; Hofmann, Alan F; Ikegawa, Shigeo

2012-04-01

The 3-sulfates of the S-acyl glutathione (GSH) conjugates of five natural bile acids (cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic) were synthesized as reference standards in order to investigate their possible formation by a rat liver cytosolic fraction. Their structures were confirmed by proton nuclear magnetic resonance, as well as by means of electrospray ionization-linear ion-trap mass spectrometry with negative-ion detection. Upon collision-induced dissociation, structurally informative product ions were observed. Using a triple-stage quadrupole instrument, selected reaction monitoring analyses by monitoring characteristic transition ions allowed the achievement of a highly sensitive and specific assay. This method was used to determine whether the 3-sulfates of the bile acid-GSH conjugates (BA-GSH) were formed when BA-GSH were incubated with a rat liver cytosolic fraction to which 3'-phosphoadenosine 5'-phosphosulfate had been added. The S-acyl linkage was rapidly hydrolyzed to form the unconjugated bile acid. A little sulfation of the GSH conjugates occurred, but greater sulfation at C-3 of the liberated bile acid occurred. Sulfation was proportional to the hydrophobicity of the unconjugated bile acid. Thus GSH conjugates of bile acids as well as their C-3 sulfates if formed in vivo are rapidly hydrolyzed by cytosolic enzymes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Protective activity of Panduratin A against Thioacetamide-induced oxidative damage: demonstration with in vitro experiments using WRL-68 liver cell line

PubMed Central

2013-01-01

Background Chalcone Panduratin A (PA) has been known for its antioxidant property, but its merits against oxidative damage in liver cells has yet to be investigated. Hence, the paper aimed at accomplishing this task with normal embryonic cell line WRL-68. Methods PA was isolated from Boesenbergia rotunda rhizomes and its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and ferric reducing power (FRAP) activities were measured in comparison with that of the standard reference drug Silymarin (SI). Oxidative damage was induced by treating the cells with 0.04 g/ml of toxic thioacetamide for 60 minutes followed by treatment with 1, 10 and 100 μg/ml concentrations of either PA or SI. The severities of oxidative stress in the control and experimental groups of cells were measured by Malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Results PA exhibited an acceptable DPPH scavenging and FRAP activities close to that of Silymarin. Treating the injured cells with PA significantly reduced the MDA level and increased the cell viability, comparable to SI. The activities of SOD, CAT and GPx were significantly elevated in the PA-treated cells in a dose dependent manner and again similar to SI. Conclusion Collectively, data suggested that PA has capacity to protect normal liver cells from oxidative damage, most likely via its antioxidant scavenging ability. PMID:24156366

Characterization of the in Vitro Metabolic Profile of Evodiamine in Human Liver Microsomes and Hepatocytes by UHPLC-Q Exactive Mass Spectrometer

PubMed Central

Zhang, Zhaowei; Fang, Tianzi; Zhou, Hongyun; Yuan, Jie; Liu, Qingwang

2018-01-01

Evodiamine is an indoloquinazoline alkaloid isolated from the fruit of Evodia rutaecarpa, which has a wide range of pharmacological effects like anti-tumor and anti-inflammatory effects. This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ultra-high performance liquid chromatography coupled with a Q Exactive mass spectrometer. A total of 12 phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes 19 metabolites, including seven phase II metabolites were detected. The structures of the metabolites were characterized based on their accurate masses, fragment ions, and chromatographic retention times. Four metabolites (M1, M2, M5, and M7) were further unambiguously confirmed by matching their retention times, accurate masses, and fragment ions with those of their reference standards. Among these metabolites, 12 metabolites are first identified (M2, M5–M8, M10–M13, and M17–M19). The current study revealed that oxygenation, N-demethylation, dehydrogenation, glucuronidation, and GSH conjugation were the major metabolic pathways for evodiamine. This study elucidated the detailed metabolite profiles of evodiamine, which is helpful in predicting in vivo metabolism of evodiamine in human and in understanding the elimination mechanism of evodiamine and in turn, the effectiveness and toxicity. PMID:29520234

Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

PubMed

Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

2015-01-01

This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients, radiation-induced liver injury may occur and affect the overall treatment plan. The total number of chemotherapy cycles correlated with liver function injury, and V35 and ALP are significant predictive factors for radiation-induced liver injury. Our dose limitation reference for liver protection is feasible.

Multipotent mesenchymal stromal cells: A promising strategy to manage alcoholic liver disease

PubMed Central

Ezquer, Fernando; Bruna, Flavia; Calligaris, Sebastián; Conget, Paulette; Ezquer, Marcelo

2016-01-01

Chronic alcohol consumption is a major cause of liver disease. The term alcoholic liver disease (ALD) refers to a spectrum of mild to severe disorders including steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. With limited therapeutic options, stem cell therapy offers significant potential for these patients. In this article, we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), based on their potential to differentiate into hepatocytes, their immunomodulatory properties, their potential to promote residual hepatocyte regeneration, and their capacity to inhibit hepatic stellate cells. The perfect match between ALD pathogenesis and MSC therapeutic mechanisms, together with encouraging, available preclinical data, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression. PMID:26755858

Early graft dysfunction and mortality rate in marginal donor liver transplantation.

PubMed

Sarkut, Pmar; Gülcü, Bariş; Işçimen, Remzi; Kiyici, Murat; Türker, Gürkan; Topal, Naile Bolca; Ozen, Yilmaz; Kaya, Ekrem

2014-01-01

To determine the effect of marginal donor livers on mortality and graft survival in liver transplantation (LT) recipients. Donors with any 1 of following were considered marginal donors: age ≥65 years, sodium level ≥ 165 mmol/L and cold ischemia time ≥ 12 h. Donors were classified according to the donor risk index (DRI) < 1.7 and ≥ 1.7. The transplant recipients' model for end-stage liver disease (MELD) scores were considered low if < 20 and high if ≥ 20. Early graft dysfunction (EGD) and mortality rate were evaluated. During the study period 47 patients underwent cadaveric LT. The mean age of the donors and recipients was 45 years (range: 5-72 years) and 46 years (range: 4-66 years), respectively. In all, there were 15 marginal donors and 18 donors with a DRI > 1.7. In total, 4 LT patients that received livers from marginal donors and 5 that received livers from donors with a DRI ≥ 1.7 had EGD. Among the recipients of marginal livers, 5 died, versus 4 of the recipients of standard livers. There was no significant difference in EGD or mortality rate between the patients that received livers from marginal donors or those with a DRI ≥ 1.7 and patients that received standard donor livers. Marginal and DRI ≥ 1.7 donors negatively affected LT outcomes, but not significantly.

Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brusko, C.S.; Marten, J.T.

1991-12-01

Environmental illness, a hypothesized disease caused by exposure to substances such as combustion products, pesticides, food additives, and Candida albicans, is discussed. The case of a patient with environmental illness and systemic candidiasis for six weeks with ketoconazole, liver enzyme concentrations increased. One month after discontinuation of ketoconazole, the liver enzyme concentrations decreased; however, over the next five months, liver enzymes and bilirubin increased. The patient developed encephalopathy and eventually was transferred to a medical center for possible liver transplant. A review of the literature pertaining to ketoconazole hepatotoxicity is also presented.16 references.

A Virtual Liver for Simulating Chemical-Induced Injury

EPA Science Inventory

The US EPA Virtual Liver – vLiver™ --is a tissue simulator that is designed to predict histopathologic lesions – the gold-standard for toxicity. We have developed an approach for a biologically motivated model of a canonical liver lobule. The simulated lobule is composed of discr...

[Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

PubMed

Restellini, Sophie; Spahr, Laurent

2012-06-27

Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

History of reference materials for food and nutrition metrology: As represented in the series of BERM Symposia

USDA-ARS?s Scientific Manuscript database

Establishment of a metrology-based measurement system requires the solid foundation of traceability of measurements to available, appropriate certified reference materials (CRM). In the early 1970s the first “biological” Reference Material (RM) of Bowens Kale, Orchard Leaves, and Bovine Liver from ...

Liver fibrosis: in vivo evaluation using intravoxel incoherent motion-derived histogram metrics with histopathologic findings at 3.0 T.

PubMed

Hu, Fubi; Yang, Ru; Huang, Zixing; Wang, Min; Zhang, Hanmei; Yan, Xu; Song, Bin

2017-12-01

To retrospectively determine the feasibility of intravoxel incoherent motion (IVIM) imaging based on histogram analysis for the staging of liver fibrosis (LF) using histopathologic findings as the reference standard. 56 consecutive patients (14 men, 42 women; age range, 15-76, years) with chronic liver diseases (CLDs) were studied using IVIM-DWI with 9 b-values (0, 25, 50, 75, 100, 150, 200, 500, 800 s/mm 2 ) at 3.0 T. Fibrosis stage was evaluated using the METAVIR scoring system. Histogram metrics including mean, standard deviation (Std), skewness, kurtosis, minimum (Min), maximum (Max), range, interquartile (Iq) range, and percentiles (10, 25, 50, 75, 90th) were extracted from apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps. All histogram metrics among different fibrosis groups were compared using one-way analysis of variance or nonparametric Kruskal-Wallis test. For significant parameters, receivers operating characteristic curve (ROC) analyses were further performed for the staging of LF. Based on their METAVIR stage, the 56 patients were reclassified into three groups as follows: F0-1 group (n = 25), F2-3 group (n = 21), and F4 group (n = 10). The mean, Iq range, percentiles (50, 75, and 90th) of D* maps between the groups were significant differences (all P < 0.05). Area under the ROC curve (AUC) of the mean, Iq range, 50, 75, and 90th percentile of D* maps for identifying significant LF (≥F2 stage) was 0.901, 0.859, 0.876, 0.943, and 0.886 (all P < 0.0001), respectively; for diagnosing severe fibrosis or cirrhosis (F4), AUC was 0.917, 0.922, 0.943, 0.985, and 0.939 (all P < 0.0001), respectively. The histogram metrics of ADC, D, and f maps demonstrated no significant difference among the groups (all P > 0.05). Histogram analysis of D* map derived from IVIM can be used to stage liver fibrosis in patients with CLDs and provide more quantitative information beyond the mean value.

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, V; Epelman, M; Feng, M

2014-06-15

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUDmore » (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.« less

Multielemental analysis in small amounts of environmental reference materials with inductively coupled plasma mass spectrometry.

PubMed

Dombovári, J; Becker, J S; Dietze, H J

2000-07-01

The lowest possible sample weight for performing multielemental trace element analysis on environmental and biological samples by ICP-MS has been investigated. The certified reference materials Bovine Liver NIST SRM 1577b, Human Hair NCS DC 73347 and Oriental Tobacco Leaves CTA-OTL-1 were applied at sample weights (1, 5, 20 and 50 mg aliquots, n = 10) which were significantly lower than those recommended with most recoveries in the range of 95-110%. Samples were digested in a mixture of nitric acid, hydrogen peroxide and hydrogen fluoride by closed-vessel microwave digestion. Multielemental analysis was performed with an optimized ICP-QMS method. Aqueous standard solutions were applied for external calibration with rhodium as the internal standard element. The detection limits varied between 0.02-0.38 microg/g for Li, Na, Cr, Mn, Ni, Cu, Zn, Sr, Cd, Ba and Pb, and up to 1.92 microg/g for Mg, Al, Ca, Fe and Ni. Digested human plasma samples were spiked with multielemental solution (0.5-10 microg/L) to test the analytical method and the recoveries were 95-105% for most analytes. Our results show that in the case of homogeneous SRMs it is possible to use them in very low amounts (1-5 mg) for method development and quality control.

Evaluation of reference genes for quantitative real-time RT-PCR analysis of gene expression in Nile tilapia (Oreochromis niloticus).

PubMed

Yang, Chang Geng; Wang, Xian Li; Tian, Juan; Liu, Wei; Wu, Fan; Jiang, Ming; Wen, Hua

2013-09-15

Quantitative real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) has been used frequently to study gene expression related to fish immunology. In such studies, a stable reference gene should be selected to correct the expression of the target gene. In this study, seven candidate reference genes (glyceraldehyde-3-phosphate dehydrogenase (GADPH), ubiquitin-conjugating enzyme (UBCE), 18S ribosomal RNA (18S rRNA), beta-2-microglobulin (B2M), elongation factor 1 alpha (EF1A), tubulin alpha chain-like (TUBA) and beta actin (ACTB)), were selected to analyze their stability and normalization in seven tissues (liver, spleen, kidney, brain, heart, muscle and intestine) of Nile tilapia (Oreochromis niloticus) challenged with Streptococcus agalactiae or Streptococcus iniae, respectively. The results showed that all the candidate reference genes exhibited tissue-dependent transcriptional variations. With PBS injection as a control, UBCE was the most stable and suitable single reference gene in the intestine, liver, brain, kidney, and spleen after S. iniae infection, and in the liver, kidney, and spleen after S. agalactiae infection. EF1A was the most suitable in heart and muscle after S. iniae or S. agalactiae infection. GADPH was the most suitable gene in intestine and brain after S. agalactiae infection. In normal conditions, UBCE and 18S rRNA were the most stably expressed genes across the various tissues. These results showed that for RT-qPCR analysis of tilapia, selecting two or more reference genes may be more suitable for cross-tissue analysis of gene expression. Copyright © 2013 Elsevier B.V. All rights reserved.

Current state of knowledge of hepatic encephalopathy (part IV): Management of Hepatic Encephalopathy by liver support systems.

PubMed

Hassanein, Tarek

2017-04-01

Hepatic Encephalopathy is a devastating complication of End-Stage Liver Disease. In its severe grades it requires extra intervention beyond the standard medical approaches. In this article were view the role of liver support systems in managing hepatic encephalopthy.

Assessment of metabolic stability using the rainbow trout (Oncorhynchus mykiss) liver S9 fraction

EPA Science Inventory

Standard protocols are given for assessing metabolic stability in rainbow trout using the liver S9 fraction. These protocols describe the isolation of S9 fractions from trout livers, evaluation of metabolic stability using a substrate depletion approach, and expression of the res...

"Klebsiella Pneumonia" Liver Abscess Syndrome: Case Presentation to a College Student Health Clinic

ERIC Educational Resources Information Center

Woll, Christopher; Spotts, P. Hunter

2016-01-01

The authors describe a case of "Klebsiella pneumoniae" liver abscess (KPLA) in a student presenting to a university student health center. The authors also provide a review of KPLA and invasive "Klebsiella pneumoniae" liver abscess syndrome (IKPLAS), including epidemiology, common clinical manifestations, standard diagnostic…

A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease

PubMed Central

Paige, Jeremy S.; Bernstein, Gregory S.; Heba, Elhamy; Costa, Eduardo A. C.; Fereirra, Marilia; Wolfson, Tanya; Gamst, Anthony C.; Valasek, Mark A.; Lin, Grace Y.; Han, Aiguo; Erdman, John W.; O’Brien, William D.; Andre, Michael P.; Loomba, Rohit; Sirlin, Claude B.

2017-01-01

OBJECTIVE The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift–based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. RESULTS CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). CONCLUSION Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD. PMID:28267360

A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease.

PubMed

Paige, Jeremy S; Bernstein, Gregory S; Heba, Elhamy; Costa, Eduardo A C; Fereirra, Marilia; Wolfson, Tanya; Gamst, Anthony C; Valasek, Mark A; Lin, Grace Y; Han, Aiguo; Erdman, John W; O'Brien, William D; Andre, Michael P; Loomba, Rohit; Sirlin, Claude B

2017-05-01

The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.

Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder.

PubMed

Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

2009-06-21

Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

Underappreciation of non-alcoholic fatty liver disease by primary care clinicians: limited awareness of surrogate markers of fibrosis.

PubMed

Patel, Preya J; Banh, Xuan; Horsfall, Leigh U; Hayward, Kelly L; Hossain, Fabrina; Johnson, Tracey; Stuart, Katherine A; Brown, Nigel N; Saad, Nivene; Clouston, Andrew; Irvine, Katharine M; Russell, Anthony W; Valery, Patricia C; Williams, Suzanne; Powell, Elizabeth E

2018-02-01

Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. To evaluate primary care clinicians' current approach to diagnosis, management and referral of NAFLD. A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed. © 2017 Royal Australasian College of Physicians.

Prevalence of liver diseases as referred by people living in the Santos and São Vicente Estuary.

PubMed

Carvalho, Daniele Fernandes Pena; Guimarães, M T; Ribeiro, T S; Campina, N N; Lobarinhas, M R; Lopes, A L J; Cunha, M G; Souza, I B; Oliveira, V L F; Braga E Braga, L; Martins, L C; Gomes, A; Pereira, L A A; Braga, A L F

2015-10-01

The Santos and São Vicente Estuary has suffered extensively over the years from irregular industrial deposits. The present study aimed to evaluate liver disease prevalence and potential associated risk factors in four of the Estuary's areas (Pilões and Água-Fria, Cubatão Center, Continental São Vicente, and Guarujá) and a reference area (Bertioga). This study consisted of a cross-sectional study design, in which a questionnaire was used to collect information in 820 households at each of the study areas. The proportion of total liver diseases, hepatitis, cirrhosis, and cancer (liver, biliary tract, and pancreas) per area were estimated. Pearson's chi-square test and two proportion differences test were applied in order to evaluate associations between disease occurrence and areas and to test differences between two proportions, respectively. Single and multiple logistic regression models were applied to assess associations between disease prevalence and the different study areas. Liver disease prevalence was 1.5 % among all inhabitants and 1.4 % among those without any type of exposure. Among those who reported the presence of liver disease, a higher percentage of the participants that reported hepatitis (27.7 %) or other liver disease (48.7 %) did not report occupational or alcohol exposures. Hepatitis (77.8 %) was the most reported disease, and a statistical association between living in Pilões and Água-Fria and the occurrence of hepatitis was observed (Pearson's χ (2): z = 18.1; p = 0.001). The consumption of locally-produced groceries (2.88; CI: 1.24-6.70) and water (5.88; CI: 2.24-15.45) were shown to be risk factors for the occurrence of liver disease. Thus, environmental exposure is still a public health problem present in the estuary region.

Liver fibrosis: a compilation on the biomarkers status and their significance during disease progression

PubMed Central

Nallagangula, Krishna Sumanth; Nagaraj, Shashidhar Kurpad; Venkataswamy, Lakshmaiah; Chandrappa, Muninarayana

2018-01-01

Liver fibrosis occurs in response to different etiologies of chronic liver injury. Diagnosing degree of liver fibrosis is a crucial step in evaluation of severity of the disease. An invasive liver biopsy is the gold standard method associated with pain and complications. Biomarkers to detect liver fibrosis include direct markers of extracellular matrix turnover and indirect markers as a reflection of liver dysfunction. Although a single marker may not be useful for successful management, a mathematical equation combining tests might be effective. The main purpose of this review is to understand the diagnostic accuracy of biomarkers and scoring systems for liver fibrosis. Advances in -omics approach have generated clinically significant biomarker candidates for liver fibrosis that need further evaluation. PMID:29255622

3.0 Tesla magnetic resonance imaging: A new standard in liver imaging?

PubMed Central

Girometti, Rossano

2015-01-01

An ever-increasing number of 3.0 Tesla (T) magnets are installed worldwide. Moving from the standard of 1.5 T to higher field strength implies a number of potential advantage and drawbacks, requiring careful optimization of imaging protocols or implementation of novel hardware components. Clinical practice and literature review suggest that state-of-the-art 3.0 T is equivalent to 1.5 T in the assessment of focal liver lesions and diffuse liver disease. Therefore, further technical improvements are needed in order to fully exploit the potential of higher field strength. PMID:26244063

3.0 Tesla magnetic resonance imaging: A new standard in liver imaging?

PubMed

Girometti, Rossano

2015-07-28

An ever-increasing number of 3.0 Tesla (T) magnets are installed worldwide. Moving from the standard of 1.5 T to higher field strength implies a number of potential advantage and drawbacks, requiring careful optimization of imaging protocols or implementation of novel hardware components. Clinical practice and literature review suggest that state-of-the-art 3.0 T is equivalent to 1.5 T in the assessment of focal liver lesions and diffuse liver disease. Therefore, further technical improvements are needed in order to fully exploit the potential of higher field strength.

Segmentation of liver region with tumorous tissues

NASA Astrophysics Data System (ADS)

Zhang, Xuejun; Lee, Gobert; Tajima, Tetsuji; Kitagawa, Teruhiko; Kanematsu, Masayuki; Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Yokoyama, Ryujiro; Kondo, Hiroshi; Hoshi, Hiroaki; Nawano, Shigeru; Shinozaki, Kenji

2007-03-01

Segmentation of an abnormal liver region based on CT or MR images is a crucial step in surgical planning. However, precisely carrying out this step remains a challenge due to either connectivities of the liver to other organs or the shape, internal texture, and homogeneity of liver that maybe extensively affected in case of liver diseases. Here, we propose a non-density based method for extracting the liver region containing tumor tissues by edge detection processing. False extracted regions are eliminated by a shape analysis method and thresholding processing. If the multi-phased images are available then the overall outcome of segmentation can be improved by subtracting two phase images, and the connectivities can be further eliminated by referring to the intensity on another phase image. Within an edge liver map, tumor candidates are identified by their different gray values relative to the liver. After elimination of the small and nonspherical over-extracted regions, the final liver region integrates the tumor region with the liver tissue. In our experiment, 40 cases of MDCT images were used and the result showed that our fully automatic method for the segmentation of liver region is effective and robust despite the presence of hepatic tumors within the liver.

Report of the 22nd Annual Congress of the International Liver Transplantation Society.

PubMed

Diaz, Geraldine C; Zerillo, Jeron; Singhal, Ashish; Hibi, Taizo; Vitale, Alessandro; Levitsky, Josh; Renz, John F

2017-02-01

The 2016 Annual Congress of the International Liver Transplantation Society was held in Seoul, South Korea in May. The 22nd Congress marked the largest multidisciplinary liver transplantation meeting in Asia since 2010. The principal themes were living donation, allocation, immunosuppression, machine preservation, novel treatment of hepatitis C, and expansion of the deceased-donor allograft pool. This report presents select abstracts from the scientific sessions within the context of the published literature to serve as a quick reference.

3D molecular MR imaging of liver fibrosis and response to rapamycin therapy in a bile duct ligation rat model.

PubMed

Farrar, Christian T; DePeralta, Danielle K; Day, Helen; Rietz, Tyson A; Wei, Lan; Lauwers, Gregory Y; Keil, Boris; Subramaniam, Arun; Sinskey, Anthony J; Tanabe, Kenneth K; Fuchs, Bryan C; Caravan, Peter

2015-09-01

Liver biopsy, the gold standard for assessing liver fibrosis, suffers from limitations due to sampling error and invasiveness. There is therefore a critical need for methods to non-invasively quantify fibrosis throughout the entire liver. The goal of this study was to use molecular Magnetic Resonance Imaging (MRI) of Type I collagen to non-invasively image liver fibrosis and assess response to rapamycin therapy. Liver fibrosis was induced in rats by bile duct ligation (BDL). MRI was performed 4, 10, or 18 days following BDL. Some BDL rats were treated daily with rapamycin starting on day 4 and imaged on day 18. A three-dimensional (3D) inversion recovery MRI sequence was used to quantify the change in liver longitudinal relaxation rate (ΔR1) induced by the collagen-targeted probe EP-3533. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for Sirius Red staining and hydroxyproline content. ΔR1 increased significantly with time following BDL compared to controls in agreement with ex vivo measures of increasing fibrosis. Receiver operating characteristic curve analysis demonstrated the ability of ΔR1 to detect liver fibrosis and distinguish intermediate and late stages of fibrosis. EP-3533 MRI correctly characterized the response to rapamycin in 11 out of 12 treated rats compared to the standard of collagen proportional area (CPA). 3D MRI enabled characterization of disease heterogeneity throughout the whole liver. EP-3533 allowed for staging of liver fibrosis, assessment of response to rapamycin therapy, and demonstrated the ability to detect heterogeneity in liver fibrosis. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Evaluation of liver regeneration diet supplemented with omega-3 fatty acids: experimental study in rats.

PubMed

Silva, Rosilda Mendes da; Malafaia, Osvaldo; Torres, Orlando Jorge Martins; Czeczko, Nicolau Gregori; Marinho Junior, Carlos Hespanha; Kozlowski, Ronaldo Kiviatcoski

2015-01-01

to evaluate liver regeneration in rats after partial hepatectomy of 60% with and without action diet supplemented with fatty acids through the study of the regenerated liver weight, laboratory parameters of liver function and histological study. thirty-six Wistar rats, males, adults were used, weighing between 195 and 330 g assigned to control and groups. The supplementation group received the diet by gavage and were killed after 24h, 72h and seven days. Evaluation of regeneration occurred through analysis of weight gain liver, serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase, and mitosis of the liver stained with H&E. the diet supplemented group showed no statistical difference (p>0.05) on the evolution of weights. Administration of fatty acids post-hepatectomy had significant reduction in gamma glutamyltransferase levels and may reflect liver regeneration. Referring to mitotic index, it did not differ between period of times among the groups. supplementation with fatty acids in rats undergoing 60% hepatic resection showed no significant interference related to liver regeneration.

Endogenous Klebsiella endophthalmitis associated with liver abscess: first case report from iran.

PubMed

Dehghani, A R; Masjedi, A; Fazel, F; Ghanbari, H; Akhlaghi, M; Karbasi, N

2011-01-07

To report the first case of endogenous Klebsiella endophthalmitis associated with liver abscess in Iran. A 79-year-old man was referred to our hospital due to severe pain and visual loss in the left eye. On physical examination, conjunctival hyperemia, corneal edema, hypopyon and severe vitreous cellular reaction were identified in the left eye; however, yellowish conjunctival discoloration was more apparent in the right eye. Abdominal CT scan showed a right liver lobe abscess that was confirmed by sonographically guided percutaneous liver mass biopsy. Blood, vitreous and liver mass aspirate cultures revealed Klebsiella pneumoniae growth. The patient was thus diagnosed with endogenous Klebsiella endophthalmitis secondary to bacteremia associated with liver abscess. This report suggests that, rather than being confined to Taiwan, endogenous endophthalmitis secondary to a liver abscess due to K. pneumoniae may be a global problem. Therefore, physicians should be aware of the possibility of endophthalmitis whenever a patient with K. pneumoniae liver abscess complains of ocular symptoms.

Pneumocystis jirovecii pneumonia in liver transplant recipients: a systematic review.

PubMed

Kostakis, I D; Sotiropoulos, G C; Kouraklis, G

2014-11-01

Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients. We searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms "liver transplantation" and "pneumocystis." Our search yielded 60 articles, 35 of which were used for our review. P. jirovecii pneumonia (PJP) has an incidence of 1%-11% in liver transplant recipients without prophylaxis and mortality rates of 7%-88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%-3%. The duration of its use varies from 3 months to 1 year after the liver transplantation. PJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.

γγ coincidence spectrometer for instrumental neutron-activation analysis

NASA Astrophysics Data System (ADS)

Tomlin, B. E.; Zeisler, R.; Lindstrom, R. M.

2008-05-01

Neutron-activation analysis (NAA) is an important technique for the accurate and precise determination of trace and ultra-trace elemental compositions. The application of γγ coincidence counting to NAA in order to enhance specificity was first explored over 40 years ago but has not evolved into a regularly used technique. A γγ coincidence spectrometer has been constructed at the National Institute of Standards and Technology, using two HPGe γ-ray detectors and an all-digital data-acquisition system, for the purpose of exploring coincidence NAA and its value in characterizing reference materials. This paper describes the initial evaluation of the quantitative precision of coincidence counting versus singles spectrometry, based upon a sample of neutron-irradiated bovine liver material.

Photoacoustic physio-chemical analysis of liver conditions in animal and human subjects

NASA Astrophysics Data System (ADS)

Wang, Xueding; Xu, Guan; Tian, Chao; Wan, Shanshan; Welling, Theodore H.; Lok, Anna S. F.; Rubin, Jonathan M.

2016-03-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease affecting 30% of the population in the United States. Biopsy is the gold standard for diagnosing NAFLD. Liver histology assesses the amount of fat, and determines type and extent of cell injury, inflammation and fibrosis. However, liver biopsy is invasive and is limited by sampling error. Current radiological diagnostic modalities can evaluate the 'physical' morphology in liver by quantifying the backscattered US signals, but cannot interrogate the 'histochemical' components forming these backscatterers. For example, ultrasound (US) imaging can detect the presence of fat but cannot differentiate steatosis alone from steatohepatitis. Our previous study of photoacoustic physiochemical analysis (PAPCA) has demonstrated that this method can characterize the histological changes in livers during the progression of NAFLD in animal models. In this study, we will further validate PAPCA with human livers. Ex vivo human liver samples with steatosis, fibrosis and cirrhosis will be scanned using optical illumination at wavelengths of 680-1700 nm and compared to histology results. In vivo study on human subjects with confirmed steatosis is planned using our PA-ultrasound (US) parallel imaging system based on Verasonic US imaging flatform with an L7-4 probe. 10 mJ/cm2 per pulse optical energy at 755 nm will be delivered to the skin surface, which is under the safety limit of American National Standard Institute. Preliminary study with ex vivo human tissue has demonstrated the potential of the proposed approach in differentiating human liver conditions.

Managing non-alcoholic fatty liver disease

PubMed Central

Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

2016-01-01

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

Methodology to assess clinical liver safety data.

PubMed

Merz, Michael; Lee, Kwan R; Kullak-Ublick, Gerd A; Brueckner, Andreas; Watkins, Paul B

2014-11-01

Analysis of liver safety data has to be multivariate by nature and needs to take into account time dependency of observations. Current standard tools for liver safety assessment such as summary tables, individual data listings, and narratives address these requirements to a limited extent only. Using graphics in the context of a systematic workflow including predefined graph templates is a valuable addition to standard instruments, helping to ensure completeness of evaluation, and supporting both hypothesis generation and testing. Employing graphical workflows interactively allows analysis in a team-based setting and facilitates identification of the most suitable graphics for publishing and regulatory reporting. Another important tool is statistical outlier detection, accounting for the fact that for assessment of Drug-Induced Liver Injury, identification and thorough evaluation of extreme values has much more relevance than measures of central tendency in the data. Taken together, systematical graphical data exploration and statistical outlier detection may have the potential to significantly improve assessment and interpretation of clinical liver safety data. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.

Ellagic acid impedes carbontetrachloride-induced liver damage in rats through suppression of NF-kB, Bcl-2 and regulating Nrf-2 and caspase pathway.

PubMed

Aslan, Abdullah; Gok, Ozlem; Erman, Orhan; Kuloglu, Tuncay

2018-06-11

The use of natural antioxidants instead of conventional treatments is considered effective and safe alternative therapy for hepatotoxicity. Ellagic acid (EA) is a strong antioxidant matter having protecting effect particularly on the liver. Hepatotoxic compounds can cause very heavy damage. Among these chemical hepatotoxins, CCl 4 are responsible for the trichloromethyl radical resulting from biotransformation of the liver. The aim of this study was to examine whether EA plays a protective role against to liver damage induced with carbon tetrachloride (CCl 4 ) in rats. In this study, 36 male wistar albino (n = 36, 8 weeks old) rats were used. The rats were distributed into 4 groups, and 9 rats involved in each group. The groups were: (i) Control Group: Fed with standard diet; (ii) EA Group: Fed with standard diet + EA; (iii) CCl 4 Group: Fed with standard diet + CCl 4 ; (iv) CCl 4 + EA Group: Fed with standard diet + CCl 4 + EA. After 8 weeks, the rats were decapitated and the liver tissue were examined. As a result; EA application created a significant difference (p < 0.05) on caspase-3, bcl-2, NF-kB and Nrf-2 expression in the CCl 4 + EA group in comparison to CCl 4 group. Caspase-3 and Nrf-2 expression levels were increased in the CCl 4 + EA group in comparison to CCl 4 group, but bcl-2 and NF-kB expression levels were decreased. In TUNEL assay examinations, apoptotic index ratio was decreased in the CCl 4 + EA group in comparison to CCl 4 group. These results show that EA reduce liver damage ratio at wistar albino rats and also these results suggest that ellagic acid may be a potentially protective drug against to liver damage in future. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical Shift MR Imaging Methods for the Quantification of Transcatheter Lipiodol Delivery to the Liver: Preclinical Feasibility Studies in a Rodent Model

PubMed Central

Yin, Xiaoming; Guo, Yang; Li, Weiguo; Huo, Eugene; Zhang, Zhuoli; Nicolai, Jodi; Kleps, Robert A.; Hernando, Diego; Katsaggelos, Aggelos K.; Omary, Reed A.

2012-01-01

Purpose: To demonstrate the feasibility of using chemical shift magnetic resonance (MR) imaging fat-water separation methods for quantitative estimation of transcatheter lipiodol delivery to liver tissues. Materials and Methods: Studies were performed in accordance with institutional Animal Care and Use Committee guidelines. Proton nuclear MR spectroscopy was first performed to identify lipiodol spectral peaks and relative amplitudes. Next, phantoms were constructed with increasing lipiodol-water volume fractions. A multiecho chemical shift–based fat-water separation method was used to quantify lipiodol concentration within each phantom. Six rats served as controls; 18 rats underwent catheterization with digital subtraction angiography guidance for intraportal infusion of a 15%, 30%, or 50% by volume lipiodol-saline mixture. MR imaging measurements were used to quantify lipiodol delivery to each rat liver. Lipiodol concentration maps were reconstructed by using both single-peak and multipeak chemical shift models. Intraclass and Spearman correlation coefficients were calculated for statistical comparison of MR imaging–based lipiodol concentration and volume measurements to reference standards (known lipiodol phantom compositions and the infused lipiodol dose during rat studies). Results: Both single-peak and multipeak measurements were well correlated to phantom lipiodol concentrations (r2 > 0.99). Lipiodol volume measurements were progressively and significantly higher when comparing between animals receiving different doses (P < .05 for each comparison). MR imaging–based lipiodol volume measurements strongly correlated with infused dose (intraclass correlation coefficients > 0.93, P < .001) with both single- and multipeak approaches. Conclusion: Chemical shift MR imaging fat-water separation methods can be used for quantitative measurements of lipiodol delivery to liver tissues. © RSNA, 2012 PMID:22623693

Quantitative Chemical Shift-Encoded MRI Is an Accurate Method to Quantify Hepatic Steatosis

PubMed Central

Kühn, Jens-Peter; Hernando, Diego; Mensel, Birger; Krüger, Paul C.; Ittermann, Till; Mayerle, Julia; Hosten, Norbert; Reeder, Scott B.

2014-01-01

Purpose To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard. Materials and Methods Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression. Results The spectroscopic range of liver fat was 0.11%–38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R2=0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P=0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P=0.528; intercept: 0.26% ± 0.46%, P=0.572). Conclusion Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements. PMID:24123655

Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic steatosis.

PubMed

Kühn, Jens-Peter; Hernando, Diego; Mensel, Birger; Krüger, Paul C; Ittermann, Till; Mayerle, Julia; Hosten, Norbert; Reeder, Scott B

2014-06-01

To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard. Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression. The spectroscopic range of liver fat was 0.11%-38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R(2)  = 0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P = 0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P = 0.528; intercept: 0.26% ± 0.46%, P = 0.572). Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements. Copyright © 2013 Wiley Periodicals, Inc.

COMPARATIVE STUDY OF FIB-4 INDEX AND TRANSIENT ELASTOGRAPHY AMONG PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION IN GEORGIA.

PubMed

Dolmazashvili, E; Karchava, M; Abutidze, A; Sharvadze, L; Tsertsvadze, T

2017-03-01

Liver biopsy remains the reference standard for fibrosis staging. However, it has several limitations, which have led to the development of non-invasive methods. We evaluated liver fibrosis severity among HCV infected patients by comparing transient elastography (TE) and FIB-4 index. Retrospective study was conducted. Clinical data for 750 patients were obtained. The mean age of the study population was 51 years; 595 (79.3%) were male and 155 (20.7%) were female. TE and tests on biological samples were performed within one-week timeframe. Additional analyses of prothrombin index, albumin concentration, splenomegaly on abdominal ultrasound and esophageal varices on upper gastrointestinal endoscopy were performed among selected patients. Comparable results were observed among 534 patients (71.2%). FIB-4<1.45 had a negative predictive value of 89% to exclude significant fibrosis and FIB-4>3.25 had a positive predictive value of 100 % to confirm the existence of significant fibrosis. Inconclusive FIB-4 score was obtained in 170 (22.7%) patients. Of them 127 (74.7%) had significant fibrosis (F3-F4) by TE. Discordant results (FIB-4 <1.45 and Liver Stiffness Measurement (LSM) >9.5 kpa) were observed in 46 (6.1%) of patients. Low prothrombin index, low albumin concentration, splenomegaly and esophageal varices were significantly (p<0.001) correlated with TE results. Discrepancy showing high FIB-4 score and low LSM was not observed in our cohort. There was a good correlation between TE and FIB-4 score. FIB-4 could rapidly replace expensive methods to assess liver fibrosis severity in some scenarios. However, our study demonstrated superiority of TE. LSM correlated better with indirect markers of significant fibrosis.

Nonalcoholic Fatty Liver Disease: MR Imaging of Liver Proton Density Fat Fraction to Assess Hepatic Steatosis

PubMed Central

Tang, An; Tan, Justin; Sun, Mark; Hamilton, Gavin; Bydder, Mark; Wolfson, Tanya; Gamst, Anthony C.; Middleton, Michael; Brunt, Elizabeth M.; Loomba, Rohit; Lavine, Joel E.; Schwimmer, Jeffrey B.

2013-01-01

Purpose: To evaluate the diagnostic performance of magnetic resonance (MR) imaging–estimated proton density fat fraction (PDFF) for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) by using centrally scored histopathologic validation as the reference standard. Materials and Methods: This prospectively designed, cross-sectional, internal review board–approved, HIPAA-compliant study was conducted in 77 patients who had NAFLD and liver biopsy. MR imaging–PDFF was estimated from magnitude-based low flip angle multiecho gradient-recalled echo images after T2* correction and multifrequency fat modeling. Histopathologic scoring was obtained by consensus of the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network Pathology Committee. Spearman correlation, additivity and variance stabilization for regression for exploring the effect of a number of potential confounders, and receiver operating characteristic analyses were performed. Results: Liver MR imaging–PDFF was systematically higher, with higher histologic steatosis grade (P < .001), and was significantly correlated with histologic steatosis grade (ρ = 0.69, P < .001). The correlation was not confounded by age, sex, lobular inflammation, hepatocellular ballooning, NASH diagnosis, fibrosis, or magnetic field strength (P = .65). Area under the receiver operating characteristic curves was 0.989 (95% confidence interval: 0.968, 1.000) for distinguishing patients with steatosis grade 0 (n = 5) from those with grade 1 or higher (n = 72), 0.825 (95% confidence interval: 0.734, 0.915) to distinguish those with grade 1 or lower (n = 31) from those with grade 2 or higher (n = 46), and 0.893 (95% confidence interval: 0.809, 0.977) to distinguish those with grade 2 or lower (n = 58) from those with grade 3 (n = 19). Conclusion: MR imaging–PDFF showed promise for assessment of hepatic steatosis grade in patients with NAFLD. For validation, further studies with larger sample sizes are needed. © RSNA, 2013 PMID:23382291

Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice.

PubMed

Muthulakshmi, Shanmugam; Saravanan, Ramalingam

2013-06-01

Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Portal Hypertension in Patients with Liver Cirrhosis: Diagnostic Accuracy of Spleen Stiffness.

PubMed

Takuma, Yoshitaka; Nouso, Kazuhiro; Morimoto, Youichi; Tomokuni, Junko; Sahara, Akiko; Takabatake, Hiroyuki; Matsueda, Kazuhiro; Yamamoto, Hiroshi

2016-05-01

To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of β-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis. (©) RSNA, 2015 Online supplemental material is available for this article.

[Utility of Fibroscan in the evaluation of liver fibrosis].

PubMed

Carrión, José A

2009-01-01

Chronic liver diseases produce a progressive accumulation of collagenous fiber in the liver parenchyma. For years, liver biopsy has been the gold standard to quantify liver fibrosis. Currently, non-invasive alternatives are available to quantify fibrosis. Transient elastography (TE) or Fibroscan quantifies liver rigidity, which is proportional to the grade of liver fibrosis. Studies are available that have evaluated the reliability and limitations of TE in healthy individuals, in patients with acute hepatitis, in distinct chronic liver diseases and in liver transplant recipients. TE is reliable for the diagnosis of liver cirrhosis (F4) and significant fibrosis (F2) but its values may vary according to the patient's characteristics and the etiology of the disease. TE can avoid liver biopsy in 90% of patients with cirrhosis and in up to 70% of those with significant fibrosis when combined with other non-invasive methods.

Analysis of normal and diseased liver tissue using auto-fluorescence and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Jia, Chunde; Lin, Junxiu; Kang, Youping

2003-12-01

In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver cancer patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5 nm is higher than that excited by 488.0 nm. However, for the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. These results have important reference values to explore the method of laser spectrum diagnosis.

Pilot Study to Confirm that Fat and Liver can be Distinguished by Spectroscopic Tissue Response on a Medipix-All-Resolution System-CT (MARS-CT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berg, Kyra B.; Anderson, Nigel G.; Butler, Alexandra P.

2009-07-23

NAFLD, liver component of the 'metabolic' syndrome, has become the most common liver disease in western nations. Non-invasive imaging techniques exist, but have limitations, especially in detection and quantification of mild to moderate fatty liver. In this pilot study, we produced attenuation curves from biomedical-quality projection images of liver and fat using the MARS spectroscopic-CT scanner. Difficulties obtaining attenuation spectra after reconstruction demonstrated that standard reconstruction programs do not preserve spectral information.

Herbal and Dietary Supplement Induced Liver Injury

PubMed Central

de Boer, Ynto S.; Sherker, Averell H.

2016-01-01

Summary The increase in the use of herbal and dietary supplements (HDS) over the last decades has been accompanied with an increase in the reports of HDS associated hepatotoxicity. The spectrum of HDS induced liver injury is diverse and the outcome may vary from transient liver test elevations to fulminant hepatic failure resulting in death or requiring liver transplantation. There are no validated standardized tools to establish the diagnosis, but some HDS products do have a typical clinical signature that may help to identify HDS induced liver injury. PMID:27842768

Pilot Study to Confirm that Fat and Liver can be Distinguished by Spectroscopic Tissue Response on a Medipix-All-Resolution System-CT (MARS-CT)

NASA Astrophysics Data System (ADS)

Berg, Kyra B.; Carr, James M.; Clark, Michael J.; Cook, Nick J.; Anderson, Nigel G.; Scott, Nicola J.; Butler, Alexandra P.; Butler, Philip H.; Butler, Anthony P.

2009-07-01

NAFLD, liver component of the "metabolic" syndrome, has become the most common liver disease in western nations. Non-invasive imaging techniques exist, but have limitations, especially in detection and quantification of mild to moderate fatty liver. In this pilot study, we produced attenuation curves from biomedical-quality projection images of liver and fat using the MARS spectroscopic-CT scanner. Difficulties obtaining attenuation spectra after reconstruction demonstrated that standard reconstruction programs do not preserve spectral information.

Multiplex cDNA quantification method that facilitates the standardization of gene expression data

PubMed Central

Gotoh, Osamu; Murakami, Yasufumi; Suyama, Akira

2011-01-01

Microarray-based gene expression measurement is one of the major methods for transcriptome analysis. However, current microarray data are substantially affected by microarray platforms and RNA references because of the microarray method can provide merely the relative amounts of gene expression levels. Therefore, valid comparisons of the microarray data require standardized platforms, internal and/or external controls and complicated normalizations. These requirements impose limitations on the extensive comparison of gene expression data. Here, we report an effective approach to removing the unfavorable limitations by measuring the absolute amounts of gene expression levels on common DNA microarrays. We have developed a multiplex cDNA quantification method called GEP-DEAN (Gene expression profiling by DCN-encoding-based analysis). The method was validated by using chemically synthesized DNA strands of known quantities and cDNA samples prepared from mouse liver, demonstrating that the absolute amounts of cDNA strands were successfully measured with a sensitivity of 18 zmol in a highly multiplexed manner in 7 h. PMID:21415008

Determination of mercury in ayurvedic dietary supplements that are not rasa shastra using the hydra-C direct mercury analyzer.

PubMed

Abdalla, Amir A; Smith, Robert E

2013-01-01

Mercury has been determined in Ayurvedic dietary supplements (Trifala, Trifala Guggulu, Turmeric, Mahasudarshan, Yograj, Shatawari, Hingwastika, Shatavari, and Shilajit) by inductively coupled plasma-mass spectrometry (ICP-MS) and direct mercury analysis using the Hydra-C direct mercury analyzer (Teledyne Leeman Labs Hudson, NH, USA). Similar results were obtained from the two methods, but the direct mercury analysis method was much faster and safer and required no microwave digestion (unlike ICP-MS). Levels of mercury ranged from 0.002 to 56  μ g/g in samples of dietary supplements. Standard reference materials Ephedra 3240 and tomato leaves that were from the National Institute of Standard and Technology (NIST) and dogfish liver (DOLT3) that was from the Canadian Research Council were analyzed using Hydra-C method. Average mercury recoveries were 102% (RSD% 0.0018), 100% (RSD% 0.0009), and 101% (RSD% 0.0729), respectively. Hydra-C method Limit Of Quantitation was 0.5 ng.

Determination of Mercury in Ayurvedic Dietary Supplements That Are Not Rasa Shastra Using the Hydra-C Direct Mercury Analyzer

PubMed Central

Abdalla, Amir A.; Smith, Robert E.

2013-01-01

Mercury has been determined in Ayurvedic dietary supplements (Trifala, Trifala Guggulu, Turmeric, Mahasudarshan, Yograj, Shatawari, Hingwastika, Shatavari, and Shilajit) by inductively coupled plasma-mass spectrometry (ICP-MS) and direct mercury analysis using the Hydra-C direct mercury analyzer (Teledyne Leeman Labs Hudson, NH, USA). Similar results were obtained from the two methods, but the direct mercury analysis method was much faster and safer and required no microwave digestion (unlike ICP-MS). Levels of mercury ranged from 0.002 to 56 μg/g in samples of dietary supplements. Standard reference materials Ephedra 3240 and tomato leaves that were from the National Institute of Standard and Technology (NIST) and dogfish liver (DOLT3) that was from the Canadian Research Council were analyzed using Hydra-C method. Average mercury recoveries were 102% (RSD% 0.0018), 100% (RSD% 0.0009), and 101% (RSD% 0.0729), respectively. Hydra-C method Limit Of Quantitation was 0.5 ng. PMID:23710181

Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease.

PubMed

Deng, Jie; Fishbein, Mark H; Rigsby, Cynthia K; Zhang, Gang; Schoeneman, Samantha E; Donaldson, James S

2014-11-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*W) and fat (T2*F) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*W (27.9 ± 3.5 ms) decreased, whereas T2*F (20.3 ± 5.5 ms) increased; and T2*W and T2*F became increasingly more similar when fat fraction was higher than 15-20%. Histological fat fraction measurements in ten patients were highly correlated with calibrated MRI fat fraction measurements (Pearson correlation coefficient r = 0.90 with P = 0.0004). Liver MRI using multi-point Dixon with multi-fat-peak and bi-exponential T2* modeling provided accurate fat quantification in children and young adults with non-alcoholic fatty liver disease and may be used to screen at-risk or affected individuals and to monitor disease progress noninvasively.

A Bioenergetics Systems Evaluation of Ketogenic Diet Liver Effects

PubMed Central

Hutfles, Lewis J.; Wilkins, Heather M.; Koppel, Scott J.; Weidling, Ian W.; Selfridge, J. Eva; Tan, Eephie; Thyfault, John P.; Slawson, Chad; Fenton, Aron W.; Zhu, Hao; Swerdlow, Russell H.

2018-01-01

Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics. PMID:28514599

A bioenergetics systems evaluation of ketogenic diet liver effects.

PubMed

Hutfles, Lewis J; Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Selfridge, J Eva; Tan, Eephie; Thyfault, John P; Slawson, Chad; Fenton, Aron W; Zhu, Hao; Swerdlow, Russell H

2017-09-01

Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

Quantification of liver fat in the presence of iron overload.

PubMed

Horng, Debra E; Hernando, Diego; Reeder, Scott B

2017-02-01

To evaluate the accuracy of R2* models (1/T 2 * = R2*) for chemical shift-encoded magnetic resonance imaging (CSE-MRI)-based proton density fat-fraction (PDFF) quantification in patients with fatty liver and iron overload, using MR spectroscopy (MRS) as the reference standard. Two Monte Carlo simulations were implemented to compare the root-mean-squared-error (RMSE) performance of single-R2* and dual-R2* correction in a theoretical liver environment with high iron. Fatty liver was defined as hepatic PDFF >5.6% based on MRS; only subjects with fatty liver were considered for analyses involving fat. From a group of 40 patients with known/suspected iron overload, nine patients were identified at 1.5T, and 13 at 3.0T with fatty liver. MRS linewidth measurements were used to estimate R2* values for water and fat peaks. PDFF was measured from CSE-MRI data using single-R2* and dual-R2* correction with magnitude and complex fitting. Spectroscopy-based R2* analysis demonstrated that the R2* of water and fat remain close in value, both increasing as iron overload increases: linear regression between R2* W and R2* F resulted in slope = 0.95 [0.79-1.12] (95% limits of agreement) at 1.5T and slope = 0.76 [0.49-1.03] at 3.0T. MRI-PDFF using dual-R2* correction had severe artifacts. MRI-PDFF using single-R2* correction had good agreement with MRS-PDFF: Bland-Altman analysis resulted in -0.7% (bias) ± 2.9% (95% limits of agreement) for magnitude-fit and -1.3% ± 4.3% for complex-fit at 1.5T, and -1.5% ± 8.4% for magnitude-fit and -2.2% ± 9.6% for complex-fit at 3.0T. Single-R2* modeling enables accurate PDFF quantification, even in patients with iron overload. 1 J. Magn. Reson. Imaging 2017;45:428-439. © 2016 International Society for Magnetic Resonance in Medicine.

Combining Angiogenesis-Targeted Treatments for Liver Cancer

Cancer.gov

In this trial, patients with unresectable hepatocellular carcinoma who are ineligible for a liver transplant or other local therapies will be given oral sorafenib at the standard approved dose and intravenous TRC105.

[Epithelioid hemangioendothelioma: an uncommon liver tumor].

PubMed

Pareja, Eugenia; Cortés, Miriam; Rayon, Miguel; Moya, Angel; Mir, Jose

2010-01-01

We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome. Due to its rarity, this entity should be considered when a solitary hepatic lesion is detected and should be included in the differential diagnosis with liver metastases. We highlight the infrequency of this tumor, its presentation as a solitary hepatic lesion and the indication of surgical treatment. We describe the clinical and pathological characteristics of epithelioid hemangioendothelioma of the liver and report a new case of this entity. The distinct therapeutic options are discussed. Copyright 2010 Elsevier España, S.L. All rights reserved.

Liver transplantation in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure.

PubMed

Fabiani, Giorgio; Rogacheski, Enio; Wiederkehr, Júlio César; Khouri, Jussara; Cianfarano, Andréa

2007-09-01

Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.

Klebsiella pneumoniae liver abscess and endophthalmitis

PubMed Central

Abdul-Hamid, Ayeshah; Bailey, Sarah-Jane

2013-01-01

A 36-year-old man was referred to the general medical team with endophthalmitis. He was noted to have raised inflammatory markers and deranged liver function tests on admission. Subsequent abdominal ultrasound scan revealed a liver abscess requiring percutaneous drainage. A common human pathogen, Klebsiella pneumoniae, was cultured from multiple sites. K pneumoniae has virulent serotypes (K1 and K2) that can cause primary liver abscess with metastatic infections. Cases have previously been predominantly reported in Southeast Asia but are increasing in prevalence in Europe and North America. The main known risk factor for the disease is diabetes mellitus. Swift antibiotic therapy, ophthalmology review and percutaneous drainage of any liver abscess are essential. Early recognition of the syndrome, despite potentially few initial symptoms, can significantly reduce morbidity and mortality. The authors report the first recorded case of K pneumoniae liver abscess with endophthalmitis in the UK. PMID:23559652

[Mortality and survival analysis of liver cancer in China].

PubMed

Zheng, Rongshou; Zuo, Tingting; Zeng, Hongmei; Zhang, Siwei; Chen, Wanqing

2015-09-01

Based on the cancer registry data to analyze the mortality and survival of liver cancer in China. Liver cancer data of 2011 were retrieved from the National Cancer Registry Database.Liver cancer deaths were estimated using age-specific rate by areas and gender according to the national population in 2011. Mortality data from 22 cancer registries during 2000-2011 were used to analyze the mortality trend, and data from 17 cancer registries during 2003-2005 were used for survival analysis. The estimates of liver cancer deaths were about 322 thousand in 2011 with a crude mortality rate of 23.93/10(5).There was an increasing trend of crude mortality rate of liver cancer during 2000-2011 in 22 Chinese cancer registries with an average annual percentage change of 0.7% (95%CI: 0.2%-1.2%), 1.1% in urban and 0.4% in rural areas. After age standardization with Segi's population, the mortality rate was significantly decreased, with an APC of -2.3%, -1.9% in urban and -2.2% in rural populations. The 5-year age standardized relative survival was 10.1% (95%CI: 9.5% to 10.7%), and the 1-, 3- and the 5-year observed survival rates were 27.2%, 12.7%, and 8.9%, respectively. Liver cancer is a major cancer threatening people's lives and health in China, and the liver cancer burden is still high.

Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines

PubMed Central

Manzini, Giulia; Henne-Bruns, Doris; Porzsolt, Franz; Kremer, Michael

2017-01-01

Background and aims Liver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of HCC with and without underlying cirrhosis. Methods We compared the following guidelines published after 1 January 2010: American (American Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola de Oncologia Medica (SEOM)), European (European Association for the study of liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and European Society for Medical Oncology-European Society of Digestive Oncology (ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)), Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana Oncologia Medica (AIOM)) and German (S3) guidelines. Results All guidelines recommend resection as therapy of choice in healthy liver. Guidelines based on the Barcelona Clinic Liver Cancer staging system recommend resection for single HCC<2 cm and Child-Pugh A cirrhosis and for HCC≤5 cm with normal bilirubin and portal pressure, whereas transplantation is recommended for multiple tumours between Milan criteria and for single tumours ≤5 cm and advanced liver dysfunction. Patients with HCC and Child-Pugh C cirrhosis are not candidates for transplantation. JSH guidelines recommend LR for patients with Child-Pugh A/B with HCC without tumour size restriction; APASL guidelines in general exclude patients with Child-Pugh A from transplantation. In patients with Child-Pugh B, transplantation is the second-line therapy, if resection is not possible for patients within Milan criteria. German and Italian guidelines recommend transplantation for all patients within Milan criteria. Conclusions Whereas resection is the standard therapy of HCC in healthy liver, a standard regarding the indication for LR and transplantation for HCC in cirrhotic liver does not exist, although nearly all guidelines claim to be evidence based. Surprisingly, despite European guidelines, Germany and Italy use their own national guidelines which partially differ from the European. Possible solutions of the problems are discussed. PMID:28405349

Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines.

PubMed

Manzini, Giulia; Henne-Bruns, Doris; Porzsolt, Franz; Kremer, Michael

2017-01-01

Liver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of HCC with and without underlying cirrhosis. We compared the following guidelines published after 1 January 2010: American (American Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola de Oncologia Medica (SEOM)), European (European Association for the study of liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and European Society for Medical Oncology-European Society of Digestive Oncology (ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)), Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana Oncologia Medica (AIOM)) and German (S3) guidelines. All guidelines recommend resection as therapy of choice in healthy liver. Guidelines based on the Barcelona Clinic Liver Cancer staging system recommend resection for single HCC<2 cm and Child-Pugh A cirrhosis and for HCC≤5 cm with normal bilirubin and portal pressure, whereas transplantation is recommended for multiple tumours between Milan criteria and for single tumours ≤5 cm and advanced liver dysfunction. Patients with HCC and Child-Pugh C cirrhosis are not candidates for transplantation. JSH guidelines recommend LR for patients with Child-Pugh A/B with HCC without tumour size restriction; APASL guidelines in general exclude patients with Child-Pugh A from transplantation. In patients with Child-Pugh B, transplantation is the second-line therapy, if resection is not possible for patients within Milan criteria. German and Italian guidelines recommend transplantation for all patients within Milan criteria. Whereas resection is the standard therapy of HCC in healthy liver, a standard regarding the indication for LR and transplantation for HCC in cirrhotic liver does not exist, although nearly all guidelines claim to be evidence based. Surprisingly, despite European guidelines, Germany and Italy use their own national guidelines which partially differ from the European. Possible solutions of the problems are discussed.

Comparison of solid phase extraction, saponification and gel permeation chromatography for the clean-up of microwave-assisted biological extracts in the analysis of polycyclic aromatic hydrocarbons.

PubMed

Navarro, P; Cortazar, E; Bartolomé, L; Deusto, M; Raposo, J C; Zuloaga, O; Arana, G; Etxebarria, N

2006-09-22

The feasibility of different clean-up procedures was studied for the determination of polycyclic aromatic hydrocarbons (PAHs) in biota samples such as oysters, mussels and fish liver. In this sense, once the samples were extracted--essentially with acetone and in a microwave system--and before they could be analysed by gas chromatography-mass spectrometry (GC-MS), three different approaches were studied for the clean-up step: solid phase extraction (SPE), microwave-assisted saponification (MAS) and gel permeation chromatography (GPC). The main aim of this work was to maximise the recoveries of PAHs and to minimise the presence of interfering compounds in the last extract. In the case of SPE, Florisil cartridges of 1, 2 and 5 g, and silica cartridges of 5 g were studied. In that case, and with oysters and mussels, microwave-assisted extraction and 5 g Florisil cartridges provided good results. In addition, the concentrations obtained for Standard Reference Material (SRM) NIST 2977 (mussel tissue) were in good agreement with the certified values. In the case of microwave-assisted saponification, the extracts were not as clean as those obtained with 5 g Florisil and this fact lead to overestimate the concentration of the heaviest PAHs. Finally, the cleanest extracts were obtained by GPC. The method was successfully applied to mussels, oysters and hake liver, and the results obtained for NIST 2977 (mussel tissue) were within the confidence interval of the certified reference material for most of the certified analytes.

Integrated internist - addiction medicine - hepatology model for hepatitis C management for individuals on methadone maintenance.

PubMed

Martinez, A D; Dimova, R; Marks, K M; Beeder, A B; Zeremski, M; Kreek, M J; Talal, A H

2012-01-01

Despite a high prevalence of hepatitis C virus (HCV) among drug users, HCV evaluation and treatment acceptance are extremely low among these patients when referred from drug treatment facilities for HCV management. We sought to increase HCV treatment effectiveness among patients from a methadone maintenance treatment program (MMTP) by maintaining continuity of care. We developed, instituted and retrospectively assessed the effectiveness of an integrated, co-localized care model in which an internist-addiction medicine specialist from MMTP was embedded in the hepatitis clinic. Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites. Of 401 evaluated patients, anti-HCV antibody was detected in 257, 86% of whom were older than 40 years. Hepatitis C virus RNA levels were measured in 222 patients, 65 of whom were aviremic. Of 157 patients with detectable HCV RNA, 125 were eligible for referral to the hepatitis clinic, 76 (61%) of whom accepted and adhered with the referral. Men engaged in MMTP <36 months were significantly less likely to be seen in hepatitis clinic than men in MMTP more than 36 months (odds ratio = 7.7; 95% confidence interval 2.6-22.9) or women. We evaluated liver histology in 63 patients, and 83% had moderate to advanced liver disease. Twenty-four patients initiated treatment with 19 completing and 13 (54%) achieving sustained response. In conclusion, integrated care between the MMTP and the hepatitis clinic improves adherence with HCV evaluation and treatment compared to standard referral practices. © 2010 Blackwell Publishing Ltd.

A novel assay for detecting antibodies to cytochrome P4502D6, the molecular target of liver kidney microsomal antibody type 1.

PubMed

Kerkar, N; Ma, Y; Hussain, M; Muratori, L; Targett, C; Williams, R; Bianchi, F B; Mieli-Vergani, G; Vergani, D

1999-03-04

Liver Kidney Microsomal type 1 (LKM1) antibody, the diagnostic marker of autoimmune hepatitis type 2, is also found in a proportion of patients with hepatitis C virus infection (HCV). It is detected conventionally by the subjective immunofluorescence technique. Our aim was to establish a simple and objective enzyme-linked immunosorbent assay (ELISA) that measures antibodies to cytochrome P4502D6 (CYP2D6), the target of LKM1. An indirect ELISA using eukaryotically expressed CYP2D6 was designed. Absorbance values obtained against a reference microsomal preparation were subtracted from those obtained against a microsomal preparation over-expressing CYP2D6, thus removing the non-CYP2D6-specific reaction. Sera from 51 LKM1 positive patients (21 autoimmune hepatitis and 30 with HCV infection), 111 LKM1 negative patients with chronic liver disease (including 20 with HCV infection) and 43 healthy controls were tested. Of 51 patients positive by immunofluorescence, 48 were also positive by ELISA while all the 154 LKM1 negative subjects were also negative by ELISA. There was a high degree of association between IFL and ELISA as demonstrated by a kappa reliability value of 0.96. The absorbance values by ELISA correlated with immunofluorescence LKM1 titres both in autoimmune hepatitis (r = 0.74, p < 0.001) and HCV infection (r = 0.67, p < 0.001). The simple, objective ELISA described has the potential to replace the standard immunofluorescence technique.

Protective effect of ethyl acetate fraction of Rhododendron arboreum flowers against carbon tetrachloride-induced hepatotoxicity in experimental models

PubMed Central

Verma, Neeraj; Singh, Anil P.; Amresh, G.; Sahu, P. K.; Rao, Ch. V.

2011-01-01

Objective: To evaluate the hepatoprotective potential of ethyl acetate fraction of Rhododendron arboreum (Family: Ericaceae) in Wistar rats against carbon tetrachloride (CCl4)-induced liver damage in preventive and curative models. Materials and Methods: Fraction at a dose of 100, 200, and 400 mg/kg was administered orally once daily for 14 days in CCl4-treated groups (II, III, IV, V and VI). The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), γ-glutamyltransferase (γ -GT), and bilirubin were estimated along with activities of glutathione S-transferase (GST), glutathione reductase, hepatic malondialdehyde formation, and glutathione content. Result and Discussion: The substantially elevated serum enzymatic activities of SGOT, SGPT, SALP, γ-GT, and bilirubin due to CCl4 treatment were restored toward normal in a dose-dependent manner. Meanwhile, the decreased activities of GST and glutathione reductase were also restored toward normal. In addition, ethyl acetate fraction also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4-intoxicated rats in a dose-dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post-treatment against CCl4-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethyl acetate fraction has a potent hepatoprotective action against CCl4-induced hepatic damage in rats. PMID:21713093

Protective effect of ethyl acetate fraction of Rhododendron arboreum flowers against carbon tetrachloride-induced hepatotoxicity in experimental models.

PubMed

Verma, Neeraj; Singh, Anil P; Amresh, G; Sahu, P K; Rao, Ch V

2011-05-01

To evaluate the hepatoprotective potential of ethyl acetate fraction of Rhododendron arboreum (Family: Ericaceae) in Wistar rats against carbon tetrachloride (CCl(4))-induced liver damage in preventive and curative models. Fraction at a dose of 100, 200, and 400 mg/kg was administered orally once daily for 14 days in CCl(4)-treated groups (II, III, IV, V and VI). The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), γ-glutamyltransferase (γ -GT), and bilirubin were estimated along with activities of glutathione S-transferase (GST), glutathione reductase, hepatic malondialdehyde formation, and glutathione content. The substantially elevated serum enzymatic activities of SGOT, SGPT, SALP, γ-GT, and bilirubin due to CCl(4) treatment were restored toward normal in a dose-dependent manner. Meanwhile, the decreased activities of GST and glutathione reductase were also restored toward normal. In addition, ethyl acetate fraction also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose-dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post-treatment against CCl(4)-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethyl acetate fraction has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Bimodal electric tissue ablation (BETA): a study on ablation size when the anode is placed on the peritoneum and the liver.

PubMed

Tiong, Leong U; Finnie, John W; Field, John B; Maddern, Guy J

2012-07-01

In bimodal electric tissue ablation (BETA), the cathode of the DC circuit is attached to the radiofrequency (RF) electrode to increase the surrounding tissue hydration. This will delay tissue desiccation and allowing the ablation process to continue for a longer period of time before "roll-off" occurs, resulting in larger ablations compared with standard radiofrequency ablation (RFA). Previous research showed that attaching the anode to the skin using electrosurgical grounding pads would reduce the efficacy of BETA because of the high electrical resistivity of the skin. This study investigated the ablation size produced when the anode was attached to the peritoneum (BETA-peritoneum) and the liver (BETA-liver) respectively. The anode of the DC circuit in BETA was attached to the peritoneum and the liver in a pig model using ECG dots. In BETA, 9 V of DC was provided for 10 min, after which the radiofrequency generator were switched on and both electrical circuits allowed to run concurrently until "roll-off." The size of ablations produced was compared to when the anode attached to the skin (BETA-skin) and standard RFA, respectively. The sites of anode placement were examined for local tissue injury. The transverse diameters in BETA-peritoneum and BETA-liver were significantly larger compared with BETA-skin and standard RFA, respectively (P < 0.001). The axial diameter in the BETA-peritoneum and BETA-liver groups were also larger compared with the BETA-skin and RFA groups, although the differences did not reach statistical significance (P = 0.09). Hematoxylin and eosin (H and E) examination of the peritoneum and the liver where the anode was attached showed coagulation necrosis involving the superficial epithelium and the liver capsule, respectively. BETA can be used to treat larger liver tumors more effectively and may reduce the tumor recurrence rates compared with standard RFA. The efficacy of BETA depends on ensuring good electrical conductivity between the cathode and the anode of the DC circuit. Research so far has shown that BETA works best when the anode is placed deep to the skin as the stratum corneum consisted of a layer of a-nucleated cells, which have high electrical resistivity. The liver could be the ideal location to place the anode as it has excellent electrical conductivity, therefore ensuring maximum tissue hydration around the cathode to produce the largest ablations possible. Copyright © 2012 Elsevier Inc. All rights reserved.

Puget Sound Dredged Disposal Analysis (PSDDA). Final Environmental Impact Statement Unconfined Open-Water Disposal for Dredged Material, Phase 2. (North and South Puget Sound)

DTIC Science & Technology

1989-09-01

flathead sole, rex sole, and rock sole all showed indications of blood worm infestations. One liver tumor was found in a rex sole during spring in the ZSF...concentrations Hainly in invertebrates; some trations (.01 ppb) in waters (from lOx to 42Ox reference) in fish livers ; rarely in fish of Puget Sound central...Eagle Harbor, and Sinclair fish livers , and birds in Inlet. Highest elevation industrialized ’-ban areas. along Ruston-Point Defiance Copper is a natural

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

PubMed Central

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-01-01

Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Conclusions Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. PMID:24117728

Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease.

PubMed

Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

2013-11-01

Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P < 0.05) higher screening ALT (98 ± 95) than children with liver disease other than NAFLD (86 ± 74). Advanced fibrosis was present in 11% of children. For the diagnosis of NAFLD, screening ALT two times the clinical ULN had a sensitivity of 57% and a specificity of 71%. Screening of overweight and obese children in primary care for NAFLD with referral to paediatric gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. © 2013 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Non-invasive diagnosis of advanced fibrosis and cirrhosis

PubMed Central

Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher

2014-01-01

Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases. PMID:25492996

Liver Cancer Mortality and Food Consumption in Serbia, 1991-2010: An Ecological Study.

PubMed

Ilić, Milena; Radoman, Kristina; Konević, Slavica; Ilić, Irena

2016-06-01

This paper investigates the correlation between liver cancer mortality and consumption of food-groups in Serbia. We conducted an ecological study. The study comprised the population of the Republic of Serbia (about 7.5 million inhabitants) during the period 1991-2010. This ecological study included the data on food consumption per capita which were obtained by the Household Budget Survey and mortality data for liver cancer made available by the National Statistical Office. Linear trend model was used to assess a trend of age-adjusted liver cancer mortality rates (per 100,000 persons) that were calculated by the method of direct standardization using the World Standard Population. Pearson correlation was performed to examine the association between liver cancer mortality and per capita food consumption quantified with a correlation coefficient (r value). In Serbia, over the past two decades a significantly decreasing trend of liver cancer mortality rates has been observed (p<0.001). Liver cancer mortality was significantly (p<0.01) positively correlated with animal fat, beef, wine and spirits intake (r=0.713, 0.631, 0.632 and 0.745, respectively). A weakly positive correlation between milk consumption and mortality from liver cancer (r=0.559, p<0.05) was found only among women. The strongest correlation was found between spirits consumption and liver cancer mortality rates in women (r=0.851, p<0.01). A negative correlation between coffee consumption and age-adjusted liver cancer mortality rates was found (r=0.516, p<0.05) only for the eldest men (aged 65 years or older). Correlations between liver cancer and dietary habits were observed and further effort is needed in order to investigate a possible causative association, using epidemiological analytical studies. Copyright© by the National Institute of Public Health, Prague 2015.

Standardization of Nomenclature and Causality Assessment in Drug-Induced Liver Injury: Summary of a Clinical Research Workshop

PubMed Central

Fontana, Robert J.; Seeff, Leonard B.; Andrade, Raúl J.; Björnsson, Einar; Day, Christopher P.; Serrano, Jose; Hoofnagle, Jay H.

2013-01-01

Idiosyncratic drug-induced liver injury (DILI) is an important but relatively infrequent cause of potentially severe acute and chronic liver injury. The aim of this clinical research workshop was to review and attempt to standardize the current nomenclature and terminology used in DILI research. Because DILI is a diagnosis of exclusion, selected elements of the medical history, laboratory tests, and previous reports were proposed to improve causality assessment. Definitions and diagnostic criteria regarding the onset of DILI, evolution of liver injury, risk factors, and mandatory testing versus optional testing for competing causes were reviewed. In addition, the role of intentional and inadvertent rechallenge, liver histology, and host genetic polymorphisms in establishing the diagnosis and prognosis of DILI were reviewed. Consensus was established regarding the need to develop a web-of-knowledge database that provides concise, reliable, and updated information on cases of liver injury due to drugs and herbal and dietary supplements. In addition, the need to develop drug-specific computerized causality assessment methods that are derived from prospectively phenotyped cases was a high priority. Proposed scales for grading DILI severity and assessing the likelihood of an agent causing DILI and written criteria for improving the reliability, accuracy, and reproducibility of expert opinion were reviewed. Finally, the unique challenges of assessing causality in children, patients with underlying liver disease, and subjects taking herbal and dietary supplements were discussed. Conclusion: Workshop participants concluded that multicenter referral networks enrolling patients with suspected DILI according to standardized methodologies are needed. These networks should also collect biological samples that may provide crucial insights into the mechanism(s) of DILI with the ultimate aim of preventing future cases of DILI. PMID:20564754

Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

PubMed Central

Lee, Joo Ho; Friso, Simonetta; Choi, Sang-Woon

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is defined as a pathologic accumulation of fat in the form of triglycerides (TG) in the liver (steatosis) that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis), which is referred to as non-alcoholic steatohepatitis (NASH). Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC). NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications. PMID:25195642

Sonographic assessment of petroleum-induced hepatotoxicity in Nigerians: does biochemical assessment underestimate liver damage?

PubMed

Anakwue, Angel-Mary; Anakwue, Raphael; Okeji, Mark; Idigo, Felicitas; Agwu, Kenneth; Nwogu, Uloma

2017-03-01

Exposure to petroleum products has been shown to have significant adverse effects on the liver which can manifest either as morphological or physiological changes. The aim of the study was to assess the effects of chronic exposure to some petroleum products on the liver of exposed workers using sonography and to determine whether biochemical assessments underestimated hepatotoxicity. Abdominal ultrasound was performed on 415 exposed workers in order to evaluate liver echogenicity and size. Also, biochemical assessment of the liver was done to evaluate its function. Statistically significant increase in the liver parenchymal echogenicity and the liver size was seen in the exposed workers compared with control (p ≤ 0.05). These increased as the exposure duration increased. It was also noted that out of 16.87% (N=70) exposed workers with abnormal liver echopattern, only 2.65% (N=11) had alanine aminotransferase above the reference range. The study revealed evidence of ultrasound detectable hepatotoxicity among the exposed subjects. Sonography appeared to detect petroleum products-induced hepatic toxicity more than biochemical assays suggesting that biochemical assessment may have underestimated toxicity.

Novel Antibody Targets Glypican-3 in Liver Cancer | Center for Cancer Research

Cancer.gov

New treatments for patients with liver cancer, the third most common cause of cancer-related death, are desperately needed. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and HCC tumors are particularly insensitive to chemotherapy. Surgery is the standard treatment for HCCs caught early, but only about a third of cases are identified at this stage.

Standard operating procedures in experimental liver research: thioacetamide model in mice and rats.

PubMed

Wallace, M C; Hamesch, K; Lunova, M; Kim, Y; Weiskirchen, R; Strnad, P; Friedman, S L

2015-04-01

In addition to carbon tetrachloride (CCl4), thioacetamide (TAA) represents a second widely used model for the induction of experimental liver fibrosis, but can also be employed for the development of acute liver failure and liver tumours. While TAA itself is not hepatotoxic, its reactive metabolites covalently bind to proteins and lipids thereby causing oxidative stress and centrilobular necrosis. Compared with CCl4, TAA leads to more periportal infiltrates and more pronounced ductal proliferation. While TAA has been shown to induce liver fibrosis development in several different mouse strains, wide variations in the administration routes, doses and treatment durations have been reported. Therefore, an adoption of a universal standard operating procedure for the administration of TAA is urgently needed. For that purpose, we are presenting here two TAA models (intraperitoneal administration of 150 mg/kg of TAA three times per week for 11 weeks in rats, and TAA administration in drinking water at 300 mg/L for 2-4 months in mice) with which we have had success in reliably and reproducibly developing chronic liver injury and fibrosis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets

NASA Astrophysics Data System (ADS)

Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmäng, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

2010-11-01

Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets.

PubMed

Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmaang, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

2010-01-01

Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments.

PubMed

Trojan, Jörg; Zangos, Stephan; Schnitzbauer, Andreas A

2016-04-01

Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage-adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment.

Supercooling Preservation Of The Rat Liver For Transplantation

PubMed Central

Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut

2015-01-01

The current standard for liver preservation is limited in duration. Employing a novel subzero preservation technique that includes supercooling and machine perfusion can significantly improve preservation and prolong storage times. By loading rat livers with cryoprotectants to prevent both intra- and extracellular ice formation and protect against hypothermic injury, livers can be cooled to −6 °C without freezing and kept viable for up to 96 hours. Here, we describe the procedures of loading cryoprotectants by means of subnormothermic machine perfusion (SNMP), controlled cooling to a supercooled state, followed by SNMP recovery and orthotopic liver transplantation. PMID:25692985

LiverAtlas: a unique integrated knowledge database for systems-level research of liver and hepatic disease.

PubMed

Zhang, Yanqiong; Yang, Chunyuan; Wang, Shaochuang; Chen, Tao; Li, Mansheng; Wang, Xue; Li, Dongsheng; Wang, Kang; Ma, Jie; Wu, Songfeng; Zhang, Xueli; Zhu, Yunping; Wu, Jinsheng; He, Fuchu

2013-09-01

A large amount of liver-related physiological and pathological data exist in publicly available biological and bibliographic databases, which are usually far from comprehensive or integrated. Data collection, integration and mining processes pose a great challenge to scientific researchers and clinicians interested in the liver. To address these problems, we constructed LiverAtlas (http://liveratlas.hupo.org.cn), a comprehensive resource of biomedical knowledge related to the liver and various hepatic diseases by incorporating 53 databases. In the present version, LiverAtlas covers data on liver-related genomics, transcriptomics, proteomics, metabolomics and hepatic diseases. Additionally, LiverAtlas provides a wealth of manually curated information, relevant literature citations and cross-references to other databases. Importantly, an expert-confirmed Human Liver Disease Ontology, including relevant information for 227 types of hepatic disease, has been constructed and is used to annotate LiverAtlas data. Furthermore, we have demonstrated two examples of applying LiverAtlas data to identify candidate markers for hepatocellular carcinoma (HCC) at the systems level and to develop a systems biology-based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC differential diagnosis. LiverAtlas is the most comprehensive liver and hepatic disease resource, which helps biologists and clinicians to analyse their data at the systems level and will contribute much to the biomarker discovery and diagnostic performance enhancement for liver diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Non-invasive assessment of fatty liver].

PubMed

Egresi, Anna; Lengyel, Gabriella; Hagymási, Krisztina

2015-04-05

As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response.

[Preoperative imaging/operation planning for liver surgery].

PubMed

Schoening, W N; Denecke, T; Neumann, U P

2015-12-01

The currently established standard for planning liver surgery is multistage contrast media-enhanced multidetector computed tomography (CM-CT), which as a rule enables an appropriate resection planning, e.g. a precise identification and localization of primary and secondary liver tumors as well as the anatomical relation to extrahepatic and/or intrahepatic vascular and biliary structures. Furthermore, CM-CT enables the measurement of tumor volume, total liver volume and residual liver volume after resection. Under the condition of normal liver function a residual liver volume of 25 % is nowadays considered sufficient and safe. Recent studies in patients with liver metastases of colorectal cancer showed a clear staging advantage of contrast media-enhanced magnetic resonance imaging (CM-MRI) versus CM-CT. In addition, most recent data showed that the use of liver-specific MRI contrast media further increases the sensitivity and specificity of detection of liver metastases. This imaging technology seems to lead closer to the ideal "one stop shopping" diagnostic tool in preoperative planning of liver resection.

Reference Materials for Food and Nutrition Metrology: Past, Present and Future

USDA-ARS?s Scientific Manuscript database

Establishment of a metrology-based measurement system requires the solid foundation of traceability of measurements to available, appropriate certified reference materials (CRM). In the early 1970’s the first “biological” RM of Bowens Kale, as well as Orchard Leaves and Bovine Liver SRMs, from the ...

IRIS Toxicological Review and Summary Documents for Vinyl Chloride (External Review Draft)

EPA Science Inventory

The Draft Toxicological Review was developed to evaluate both the cancer and non cancer human health risks from environmental exposure to vinyl chloride. A reference concentration (RfC), and a reference dose (RfD) were developed based upon induction of liver cell polymorphism in ...

20180312 - Reproducibility and variance of liver effects in subchronic and chronic repeat dose toxicity studies (SOT)

EPA Science Inventory

In vivo studies provide reference data to evaluate alternative methods for predicting toxicity. However, the reproducibility and variance of effects observed across multiple in vivo studies is not well understood. The US EPA’s Toxicity Reference Database (ToxRefDB) stores d...

Possible autoimmune hepatitis induced after chronic active Epstein-Barr virus infection.

PubMed

Wada, Yoshiko; Sato, Chikako; Tomita, Kyoko; Ishii-Aso, Rika; Haga, Hiroaki; Okumoto, Kazuo; Nishise, Yuko; Watanabe, Hisayoshi; Saito, Takafumi; Ueno, Yoshiyuki

2014-02-01

Chronic active Epstein-Barr virus infection (CAEBV) can be manifested in a variety of systemic conditions, including interstitial pneumonia, malignant lymphoma, and coronary aneurysm. Sometimes it may be associated with hepatic failure, although the mechanism underlying CAEBV-related hepatotoxicity remains unclear. We encountered a case of autoimmune hepatitis (AIH) associated with CAEBV. A 61-year-old male was referred to our hospital because of abnormal liver enzyme levels after initial diagnosis of CAEBV had been made by laboratory tests and liver biopsy. On admission, positivity for anti-nuclear antibody was evident, and examination of the liver biopsy specimen showed findings compatible with AIH. Steroid administration was initiated, and the liver function parameters subsequently improved. Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.

Morphology and morphometry of fetal liver at 16-26 weeks of gestation by magnetic resonance imaging: Comparison with embryonic liver at Carnegie stage 23.

PubMed

Hamabe, Yui; Hirose, Ayumi; Yamada, Shigehito; Uwabe, Chigako; Okada, Tomohisa; Togashi, Kaori; Kose, Katsumi; Takakuwa, Tetsuya

2013-06-01

Normal liver growth was described morphologically and morphometrically using magnetic resonance imaging (MRI) data of human fetuses, and compared with embryonic liver to establish a normal reference chart for clinical use. MRI images from 21 fetuses at 16-26 weeks of gestation and eight embryos at Carnegie stage (CS)23 were investigated in the present study. Using the image data, the morphology of the liver as well as its adjacent organs was extracted and reconstructed three-dimensionally. Morphometry of fetal liver growth was performed using simple regression analysis. The fundamental morphology was similar in all cases of the fetal livers examined. The liver tended to grow along the transversal axis. The four lobes were clearly recognizable in the fetal liver but not in the embryonic liver. The length of the liver along the three axes, liver volume and four lobes correlated with the bodyweight (BW). The morphogenesis of the fetal liver on the dorsal and caudal sides was affected by the growth of the abdominal organs, such as the stomach, duodenum and spleen, and retroperitoneal organs, such as the right adrenal gland and right kidney. The main blood vessels such as inferior vena cava, portal vein and umbilical vein made a groove on the surface of the liver. Morphology of the fetal liver was different from that of the embryonic liver at CS23. The present data will be useful for evaluating the development of the fetal liver and the adjacent organs that affect its morphology. © 2012 The Japan Society of Hepatology.

Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.

PubMed

Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru

2015-07-01

The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Clamp-crushing vs. radiofrequency-assisted liver resection:changes in liver function tests.

PubMed

Palibrk, Ivan; Milicic, Biljana; Stojiljkovic, Ljuba; Manojlovic, Nebojsa; Dugalic, Vladimir; Bumbasirevic, Vesna; Kalezic, Nevena; Zuvela, Marinko; Milicevic, Miroslav

2012-05-01

Liver resection is the gold standard in managing patients with metastatic or primary liver cancer. The aim of our study was to compare the traditional clamp-crushing technique to the radiofrequency- assisted liver resection technique in terms of postoperative liver function. Liver function was evaluated preoperatively and on postoperative days 3 and 7. Liver synthetic function parameters (serum albumin level, prothrombin time and international normalized ratio), markers of hepatic injury and necrosis (serum alanine aminotransferase, aspartate aminotransferase and total bilirubin level) and microsomal activity (quantitative lidocaine test) were compared. Forty three patients completed the study (14 had clamp-crushing and 29 had radiofrequency assisted liver resection). The groups did not differ in demographic characteristics, pre-operative liver function, operative time and perioperative transfusion rate. In postoperative period, there were similar changes in monitored parameters in both groups except albumin levels, that were higher in radiofrequency-assisted liver resection group (p=0.047). Both, traditional clamp-crushing technique and radiofrequency assisted liver resection technique, result in similar postoperative changes of most monitored liver function parameters.

Acute and chronic hepatobiliary manifestations of sickle cell disease: A review

PubMed Central

Shah, Rushikesh; Taborda, Cesar; Chawla, Saurabh

2017-01-01

Sickle cell disease (SCD) is a common hemoglobinopathy which can affect multiple organ systems in the body. Within the digestive tract, the hepatobiliary system is most commonly affected in SCD. The manifestations range from benign hyperbilirubinemia to overt liver failure, with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. This is an umbrella term referring to liver dysfunction and hyperbilirubinemia due to intrahepatic sickling process during SCD crisis leading to ischemia, sequestration and cholestasis. In this review, we detail the pathophysiology, clinical presentation and biochemical features of various acute and chronic hepatobiliary manifestations of SCD and present and evaluate existing evidence with regards to management of this disease process. We also discuss recent advances and controversies such as the role of liver transplantation in sickle cell hepatopathy and highlight important questions in this field which would require further research. Our aim with this review is to help increase the understanding, aid in early diagnosis and improve management of this important disease process. PMID:28868180

Chronic moderate alcohol consumption relieves high-fat high-cholesterol diet-induced liver fibrosis in a rat model.

PubMed

Sun, Furong; Zhuang, Zhenjie; Zhang, Dai; Chen, Yushuai; Liu, Shu; Gao, Nan; Shi, Junping; Wang, Bingyuan

2018-05-30

Nonalcoholic fatty liver disease is a worldwide health issue and chronic alcohol consumption may have different effects on this disease. This study explored the role of chronic moderate alcohol consumption on high-fat high-cholesterol (HFHC) diet-induced liver fibrosis in a rodent model. Male Sprague-Dawley rats were divided into five groups: standard chow group, standard chow plus Er Guo Tou (EGT, a Chinese spirits made from fermented cereals) group, HFHC group, HFHC plus EGT group, and HFHC plus pure ethanol group. Rats were fed standard chow or HFHC chow for 12 weeks. EGT or pure ethanol was administrated at a daily dose of 4 g/kg body weight via intra-gastric gavage from the week four. At the end of week 12, hematoxylin and eosin staining, Sirius red and immunohistochemistry of liver sections were examined. The hepatic expression of F4/80, TNF-α, IL-1β, IL-6, CXCL1, CXCL2, α-SMA, Collagen, TGF-β, MMP2, MMP9, and TIMP1 was calculated. Both moderate EGT and pure ethanol did not increase plasma endotoxin in the portal vein comparing with the FHFC group. EGT and pure ethanol did not improve hepatic inflammation, but ameliorated liver fibrosis in histology. Moderate EGT and pure ethanol ameliorated HFHC diet-induced activation of Kupffer cells and hepatic stellate cells. In conclusion, chronic moderate EGT and pure ethanol could ameliorate HFHC diet-induced liver fibrosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pacilio, Massimiliano, E-mail: mpacilio@scamillofo

Purpose: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. Methods: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of {sup 99m}Tc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a “liver’s segment,” or distributing multiple uptaking nodules (“nonuniform liver”), with a tumoral liver/healthy parenchyma ratio of 5:1.more » Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and {sup 99m}Tc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with {sup 90}Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the “gold standard,” GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. Results: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%–14% for a liver segment, and by 7%–12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from −10%/40% for a liver segment, and −10%/20% for a nonuniform liver, to −13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, −38%/−13% in liver’s segment, −61%/−40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: −7%/13%). Conclusions: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods.« less

Different combinations of maternal and postnatal diet are reflected in changes of hepatic parenchyma and hepatic TNF-alpha expression in male rat offspring.

PubMed

Kačarević, Željka Perić; Grgić, Anđela; Šnajder, Darija; Bijelić, Nikola; Belovari, Tatjana; Cvijanović, Olga; Blažičević, Valerija; Radić, Radivoje

2017-09-01

Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring. Copyright © 2017 Elsevier GmbH. All rights reserved.

Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology

PubMed Central

Ma, Jenson; Sandow, Tyler; Devun, Daniel; Kirsch, David; Gulotta, Paul; Gilbert, Patrick; Kay, Dennis

2017-01-01

Background: Since the early 1990s, the minimally invasive image-guided therapies used in interventional oncology to treat hepatocellular carcinoma have continued to evolve. Additionally, the range of applications has been expanded to the treatment of hepatic metastases from colorectal cancer, neuroendocrine tumors, cholangiocarcinoma, breast cancer, melanoma, and sarcoma. Methods: We searched the literature to identify publications from 1990 to the present on various image-guided intraarterial therapies and their efficacy, as well as their role in the management of primary and secondary liver malignancies. Results: Chemoembolization and radioembolization are considered a standard of care in treating, delaying progression of disease, and downstaging to bridge to liver transplantation. Progression-free survival and overall survival outcomes are promising in patients with colorectal cancer and neuroendocrine tumors with liver metastases. Applications in the treatment of hepatic metastases from cholangiocarcinoma, breast cancer, melanoma, and sarcoma also show potential. Conclusion: Interventional oncology and its image-guided intraarterial therapies continue to gain recognition as treatment options for primary and secondary liver cancers. Growing evidence supports their role as a standard of care alongside medical oncology, surgery, and radiation oncology. PMID:29230127

Effects of Persian leek (Allium ampeloprasum) on hepatic lipids and the expression of proinflammatory gene in hamsters fed a high-fat/ high-cholesterol diet.

PubMed

Fatoorechi, Vahideh; Rismanchi, Marjan; Nasrollahzadeh, Javad

2016-01-01

Persian leek is one of the most widely used herbal foods among Iranians. In this study, effects of oral administration of Persian leek on plasma and liver lipids were examined in hamster. Male Syrian hamsters were randomly divided into three groups: control (standard diet), high fat control (high-fat/high-cholesterol diet), Persian leek (high-fat/high-cholesterol diet + 1% per weight of diet from dried powdered Persian leek) for 14 weeks. High fat diet increased plasma and liver lipids as compared to standard diet. Adding Persian leek to the high-fat/high-cholesterol diet resulted in no significant changes in the concentration of the plasma lipids or liver cholesterol. However, liver triglycerides (TG), plasma Alanine aminotransferase and gene expression of tumor necrosis factor- α were decreased in hamsters fed high-fat diet containing Persian leek as compared to high-fat diet only. Persian leek might be considered as a herbal food that can reduce liver TG accumulation induced by high fat diets.

Accuracy of Estimation of Graft Size for Living-Related Liver Transplantation: First Results of a Semi-Automated Interactive Software for CT-Volumetry

PubMed Central

Mokry, Theresa; Bellemann, Nadine; Müller, Dirk; Lorenzo Bermejo, Justo; Klauß, Miriam; Stampfl, Ulrike; Radeleff, Boris; Schemmer, Peter; Kauczor, Hans-Ulrich; Sommer, Christof-Matthias

2014-01-01

Objectives To evaluate accuracy of estimated graft size for living-related liver transplantation using a semi-automated interactive software for CT-volumetry. Materials and Methods Sixteen donors for living-related liver transplantation (11 male; mean age: 38.2±9.6 years) underwent contrast-enhanced CT prior to graft removal. CT-volumetry was performed using a semi-automated interactive software (P), and compared with a manual commercial software (TR). For P, liver volumes were provided either with or without vessels. For TR, liver volumes were provided always with vessels. Intraoperative weight served as reference standard. Major study goals included analyses of volumes using absolute numbers, linear regression analyses and inter-observer agreements. Minor study goals included the description of the software workflow: degree of manual correction, speed for completion, and overall intuitiveness using five-point Likert scales: 1–markedly lower/faster/higher for P compared with TR, 2–slightly lower/faster/higher for P compared with TR, 3–identical for P and TR, 4–slightly lower/faster/higher for TR compared with P, and 5–markedly lower/faster/higher for TR compared with P. Results Liver segments II/III, II–IV and V–VIII served in 6, 3, and 7 donors as transplanted liver segments. Volumes were 642.9±368.8 ml for TR with vessels, 623.8±349.1 ml for P with vessels, and 605.2±345.8 ml for P without vessels (P<0.01). Regression equations between intraoperative weights and volumes were y = 0.94x+30.1 (R2 = 0.92; P<0.001) for TR with vessels, y = 1.00x+12.0 (R2 = 0.92; P<0.001) for P with vessels, and y = 1.01x+28.0 (R2 = 0.92; P<0.001) for P without vessels. Inter-observer agreement showed a bias of 1.8 ml for TR with vessels, 5.4 ml for P with vessels, and 4.6 ml for P without vessels. For the degree of manual correction, speed for completion and overall intuitiveness, scale values were 2.6±0.8, 2.4±0.5 and 2. Conclusions CT-volumetry performed with P can predict accurately graft size for living-related liver transplantation while improving workflow compared with TR. PMID:25330198

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Guang, E-mail: lig2@mskcc.org; Schmidtlein, C. Ross; Humm, John L.

Purpose: To assess and account for the impact of respiratory motion on the variability of activity and volume determination of liver tumor in positron emission tomography (PET) through a comparison between free-breathing (FB) and respiration-suspended (RS) PET images. Methods: As part of a PET/computed tomography (CT) guided percutaneous liver ablation procedure performed on a PET/CT scanner, a patient's breathing is suspended on a ventilator, allowing the acquisition of a near-motionless PET and CT reference images of the liver. In this study, baseline RS and FB PET/CT images of 20 patients undergoing thermal ablation were acquired. The RS PET provides near-motionlessmore » reference in a human study, and thereby allows a quantitative evaluation of the effect of respiratory motion on PET images obtained under FB conditions. Two methods were applied to calculate tumor activity and volume: (1) threshold-based segmentation (TBS), estimating the total lesion glycolysis (TLG) and the segmented volume and (2) histogram-based estimation (HBE), yielding the background-subtracted lesion (BSL) activity and associated volume. The TBS method employs 50% of the maximum standardized uptake value (SUV{sub max}) as the threshold for tumors with SUV{sub max} ≥ 2× SUV{sub liver-bkg}, and tumor activity above this threshold yields TLG{sub 50%}. The HBE method determines local PET background based on a Gaussian fit of the low SUV peak in a SUV-volume histogram, which is generated within a user-defined and optimized volume of interest containing both local background and lesion uptakes. Voxels with PET intensity above the fitted background were considered to have originated from the tumor and used to calculate the BSL activity and its associated lesion volume. Results: Respiratory motion caused SUV{sub max} to decrease from RS to FB by −15% ± 11% (p = 0.01). Using TBS method, there was also a decrease in SUV{sub mean} (−18% ± 9%, p = 0.01), but an increase in TLG{sub 50%} (18% ± 36%) and in the segmented volume (47% ± 52%, p = 0.01) from RS to FB PET images. The background uptake in normal liver was stable, 1% ± 9%. In contrast, using the HBE method, the differences in both BSL activity and BSL volume from RS to FB were −8% ± 10% (p = 0.005) and 0% ± 16% (p = 0.94), respectively. Conclusions: This is the first time that almost motion-free PET images of the human liver were acquired and compared to free-breathing PET. The BSL method's results are more consistent, for the calculation of both tumor activity and volume in RS and FB PET images, than those using conventional TBS. This suggests that the BSL method might be less sensitive to motion blurring and provides an improved estimation of tumor activity and volume in the presence of respiratory motion.« less

Dietary intake of ain-93 standard diet induces Fatty liver with altered hepatic fatty acid profile in Wistar rats.

PubMed

Farias Santos, Juliana; Suruagy Amaral, Monique; Lima Oliveira, Suzana; Porto Barbosa, Júnia; Rego Cabral, Cyro; Sofia Melo, Ingrid; Bezerra Bueno, Nassib; Duarte Freitas, Johnatan; Goulart Sant'ana, Antônio; Rocha Ataíde, Terezinha

2015-05-01

There are several standard diets for animals used in scientific research, usually conceived by scientific institutions. The AIN-93 diet is widely used, but there are some reports of fatty liver in Wistar rats fed this diet. We aimed to evaluate the hepatic repercussions of the AIN-93 diet intake in Wistar rats. Forty newly-weaned 21-day-old male Wistar rats were fed either the AIN-93 diet or a commercial diet for either 1 month or 4 months. Weight gain, serum biochemistry, hepatic histology, and hepatic fatty acid profile were analyzed. Hepatic steatosis was observed, especially in the group fed the AIN-93 diet. Serum blood glucose, absolute and relative liver weight and hepatic levels of oleic, palmitoleic, stearic, and palmitic fatty acids were related to the observed steatosis, while lipidogram and serum markers of liver function and injury were not. AIN-93 diet induced acute hepatic steatosis in Wistar rats, which may compromise its use as a standard diet for experimental studies with rodents. The hepatic fatty acid profile was associated with steatosis, with possible implications for disease prognosis. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Mouse decellularised liver scaffold improves human embryonic and induced pluripotent stem cells differentiation into hepatocyte-like cells

PubMed Central

Scottoni, Federico; Crowley, Claire; Fiadeiro, Rebeca; Maghsoudlou, Panagiotis; Pellegata, Alessandro Filippo; Mazzacuva, Francesca; Gjinovci, Asllan; Lyne, Anne-Marie; Zulini, Justine; Little, Daniel; Mosaku, Olukunbi; Kelly, Deirdre; De Coppi, Paolo; Gissen, Paul

2017-01-01

Liver transplantation is the definitive treatment of liver failure but donor organ shortage limits its availability. Stem cells are highly expandable and have the potential to differentiate into any specialist cell. Use of patient-derived induced Pluripotent Stem Cells (hiPSCs) has the additional advantage for organ regeneration therapies by removing the need for immunosuppression. We compared hepatocyte differentiation of human embryonic stem cells (hESCs) and hiPSCs in a mouse decellularised liver scaffold (3D) with standard in vitro protocol (2D). Mouse livers were decellularised preserving micro-architecture, blood vessel network and extracellular matrix. hESCs and hiPSCs were primed towards the definitive endoderm. Cells were then seeded either in 3D or 2D cultures and the hepatocyte differentiation was continued. Both hESCs and hiPSCs differentiated more efficiently in 3D than in 2D, with higher and earlier expression of mature hepatocyte marker albumin, lipid and glycogen synthesis associated with a decrease in expression of fetal hepatocyte marker alpha-fetoprotein. Thus we conclude that stem cell hepatocyte differentiation in 3D culture promotes faster cell maturation. This finding suggests that optimised 3D protocols could allow generation of mature liver cells not achieved so far in standard 2D conditions and lead to improvement in cell models of liver disease and regenerative medicine applications. PMID:29261712

Survey of patterns, levels, and trends of perfluorinated compounds in aquatic organisms and bird eggs from representative German ecosystems.

PubMed

Rüdel, Heinz; Müller, Josef; Jürling, Heinrich; Bartel-Steinbach, Martina; Koschorreck, Jan

2011-11-01

Samples from the German Environmental Specimen Bank (ESB) covering particularly the years 1994-1996, 2000-2002, and 2006-2009 were analyzed for perfluorinated compounds (PFC; mainly C4-C13 carboxylic and sulfonic acids) to gain an overview on current PFC levels and patterns in marine, limnetic, and terrestrial biota; to assess their concentrations in different trophic levels; and to investigate whether risk management measures for PFC are successful. Specimens, either standardized annual pooled samples (blue mussels, eelpout liver, bream liver, pigeon eggs) or individual single samples (cormorant eggs, rook eggs), were collected for the German ESB program from representative sampling sites according to documented guidelines. After appropriate extraction, PFC were quantified under ISO/IEC 17025 accreditation by HPLC/MS-MS with isotopically labeled internal standards. Limits of quantification (LOQs) were 0.2-0.5 ng/g. Data are reported on a wet weight basis. In most samples the predominant PFC was perfluorooctane sulfonic acid (PFOS). However, in marine mussels from North and Baltic Seas, PFOS levels were mostly below the LOQ, but low residues of PFOS amide were found which declined in recent years. Livers of eelpout showed maximum concentrations of 15-25 ng/g PFOS in the period 2000-2002 and low amounts of perfluoropentanoate in all years. Beside PFOS (median 48 ng/g) several PFC could be determined in cormorant eggs sampled in 2009 from a Baltic Sea site. For a freshwater ecosystem, current PFC burdens for cormorant eggs were even higher (median 400 ng/g PFOS). Livers of bream from rivers showed concentrations of 130-260 ng/g PFOS, but for bream from a reference lake levels were only about 6 ng/g. In contrast to cormorants, eggs of rook and feral pigeon from terrestrial ecosystems displayed only low PFC burdens (up to 6 ng/g PFOS). Generally, PFC levels were lower in marine than in freshwater biota. PFC burdens were higher in biota from the ESB-North Sea sites than in Baltic Sea organisms. Levels of PFC were quite high especially in top predators of both limnetic and marine ecosystems. Only low PFC levels were detected in eggs of terrestrial birds. A decrease of PFOS levels from maximum values around the year 2000 observed at least in North Sea biota may be a result of a production cease and shifts in marketing pattern.

Utilization of beta-carotene from Spirulina platensis by rats.

PubMed

Kapoor, R; Mehta, U

1993-01-01

The availability of beta-carotene from Spirulina as compared to standard all trans beta-carotene was studied by the liver and kidney vitamin A storage method. After 21 days of vitamin A depletion, the rats were repleted with beta-carotene from Spirulina and a standard source at two dietary levels (60 and 120 micrograms/day) for a 10 day period. At lower levels, the liver storage levels of vitamin A and the percent of beta-carotene absorption were comparable to those of the standard. At higher levels both these parameters of the Spirulina fed group were significantly (P < 0.01) inferior to the standard source fed group. However, the Spirulina fed group showed better (P < 0.05) growth than the standard fed group did at both low and high levels of feeding.

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

PubMed Central

ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

2015-01-01

Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

Diffusion-weighted and T2-weighted MR imaging for colorectal liver metastases detection in a rat model at 7 T: a comparative study using histological examination as reference.

PubMed

Wagner, Mathilde; Maggiori, Léon; Ronot, Maxime; Paradis, Valérie; Vilgrain, Valérie; Panis, Yves; Van Beers, Bernard E

2013-08-01

To compare diffusion-weighted (DW) and T2-weighted MR imaging in detecting colorectal liver metastases in a rat model, using histological examination as a reference method. Eighteen rats had four liver injections of colon cancer cells. MR examinations at 7 T included FSE-T2-weighted imaging and SE-DW MR imaging (b = 0, 20 and 150 s/mm(2)) and were analysed by two independent readers. Histological examination was performed on 0.4-mm slices. McNemar's test was used to compare the sensitivities and the Wilcoxon matched pairs test to compare the average number of false-positives per rat. One hundred and sixty-six liver metastases were identified on histological examination. The sensitivity in detecting liver metastases was significantly higher on DW MR than on T2-weighted images (99/166 (60 %) (reader 1) and 92/166 (55 %) (reader 2) versus 77/166 (46 %), P ≤ 0.001), without an increase in false-positives per rat (P = 0.773/P = 0.850). After stratification according to metastasis diameter, DW MR imaging had a significantly higher sensitivity than T2-weighted imaging only for metastases with a diameter (0.6-1.2 mm) similar to that of the spatial resolution of MR imaging in the current study. This MR study with histological correlations shows the higher sensitivity of DW relative to T2-weighted imaging at 7 T for detecting liver metastases, especially small ones. • Diffusion weighted (DW) sequences are increasingly used in magnetic resonance imaging (MRI). • DW has higher sensitivity for liver metastases than T2-weighted imaging at 7 T. • This increase in sensitivity is especially marked for small liver metastasis detection. • This higher sensitivity is confirmed in an animal model with histological correlation. • DW imaging has the potential for earlier diagnosis of small liver metastases.

Ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-12-01

This study describes the ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius). Images of the liver were obtained from the 11th to 5th intercostal spaces (ICSs). The distance between the dorsal liver margin and the midline of the back was shortest (39.1 ± 7.4 cm) at the 11th ICS and increased cranially to 5th ICS. The size of the liver was largest at the 9th ICS and smallest at the 5th ICS. In 6 camels the right kidney was visualized from the 10th and 11th ICSs and upper right flank and in the 10th and 11th ICSs in the remaining 16 camels. In all camels, the left kidney was imaged from the caudal left flank. In 21 camels, the differentiation between the renal cortex and medulla was clearly visible in the ultrasonograms. Ultrasonographic description of the liver and kidneys provides a basic reference for diagnosing hepatic and renal disorders in camels.

Ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius)

PubMed Central

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-01-01

This study describes the ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius). Images of the liver were obtained from the 11th to 5th intercostal spaces (ICSs). The distance between the dorsal liver margin and the midline of the back was shortest (39.1 ± 7.4 cm) at the 11th ICS and increased cranially to 5th ICS. The size of the liver was largest at the 9th ICS and smallest at the 5th ICS. In 6 camels the right kidney was visualized from the 10th and 11th ICSs and upper right flank and in the 10th and 11th ICSs in the remaining 16 camels. In all camels, the left kidney was imaged from the caudal left flank. In 21 camels, the differentiation between the renal cortex and medulla was clearly visible in the ultrasonograms. Ultrasonographic description of the liver and kidneys provides a basic reference for diagnosing hepatic and renal disorders in camels. PMID:23729824

Cystic Fibrosis Associated with Worse Survival After Liver Transplantation.

PubMed

Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don

2016-04-01

Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

New Concepts on Pathogenesis and Diagnosis of Liver Fibrosis; A Review Article

PubMed Central

Ebrahimi, Hedyeh; Naderian, Mohammadreza; Sohrabpour, Amir Ali

2016-01-01

Liver fibrosis is a potentially reversible response to hepatic insults, triggered by different chronic diseases most importantly viral hepatitis, alcoholic, and nonalcoholic fatty liver disease. In the course of the chronic liver disease, hepatic fibrogenesis may develop, which is attributed to various types of cells, molecules, and pathways. Activated hepatic stellate cell (HSC), the primary source of extracellular matrix (ECM), is fundamental in pathophysiology of fibrogenesis, and thus is the most attractable target for reversing liver fibrosis. Although, liver biopsy has long been considered as the gold standard for diagnosis and staging of hepatic fibrosis, assessing progression and regression by biopsy is hampered by its limitations. We provide recent views on noninvasive approaches including serum biomarkers and radiologic techniques. PMID:27698966

Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates.

PubMed

Clark, D B; Lynch, K G; Donovan, J E; Block, G D

2001-09-01

Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.

Review on liver inflammation and antiinflammatory activity of Andrographis paniculata for hepatoprotection.

PubMed

Chua, Lee Suan

2014-11-01

Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation. Copyright © 2014 John Wiley & Sons, Ltd.

Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments

PubMed Central

Trojan, Jörg; Zangos, Stephan; Schnitzbauer, Andreas A.

2016-01-01

Background Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. Methods A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. Results The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage-adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. Conclusion Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment. PMID:27413729

Fatty liver in children

PubMed Central

Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

2009-01-01

Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 1500 children who were investigated, 34 subjects with sonographic evidence of fatty liver were enrolled in this study (2.3%). The mean age was 6.53 ± 3.07 years. Elevated aspartate aminotransferase and alanine aminotransferase was detected in 38.2% and 47.1% of patients, respectively. The mean level of cholesterol was 461 ± 182.23 mg/dl and 94.1% of patients had hypercholesterolemia. Total cholesterol level and serum aminotransferase levels had a significant positive correlation with severity of fatty liver (p < 0.05). Mean body mass index was significantly higher in patients with severe fatty liver (p < 0.05). Conclusion: The epidemiology of pediatric NAFLD should inform future attempts to develop evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology of fatty liver in children. PMID:19536316

Ultrasonographic anatomy of the healthy southern tigrina ( Leopardus guttulus) abdomen: comparison with domestic cat references.

PubMed

Müller, Thiago R; Marcelino, Raquel S; de Souza, Livia P; Teixeira, Carlos R; Mamprim, Maria J

2017-02-01

Objectives The aim of the study was to describe the normal abdominal echoanatomy of the tigrina and to compare it with the abdominal echoanatomy of the domestic cat. Reference intervals for the normal abdominal ultrasonographic anatomy of individual species are important for accurate diagnoses and interpretation of routine health examinations. The hypothesis was that the echoanatomy of the tigrina was similar to that of the domestic cat. Methods Eighteen clinically healthy tigrina were selected for abdominal ultrasound examination, in order to obtain normal parameters of the bladder, spleen, adrenal gland, kidney, gastrointestinal tract, liver and gall bladder, and Doppler parameters of liver and kidney vessels. Results The splenic parenchyma was consistently hyperechoic to the kidneys and liver. The liver, kidneys and spleen had similar echotexture, shape and dimensions when compared with the domestic cat. The gall bladder was lobulated and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The adrenal glands had a bilobulated shape. The urinary bladder had a thin echogenic wall. The Doppler parameters of the portal vein and renal artery were similar to the domestic cat. Conclusions and relevance The results support the hypothesis that the ultrasonographic parameters of the abdominal viscera of the southern tigrina are similar to those of the domestic cat.

Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review.

PubMed

Rustad, James K; Stern, Theodore A; Prabhakar, Maithri; Musselman, Dominique

2015-01-01

Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have more than double the prevalence of steatohepatitis or rejection on biopsy and graft failure and more frequent mortality resulting from recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest drinking at 6y posttransplantation) alcohol users do. Fortunately, pretransplantation screening combined with a structured pretransplantation management program and a 12-step program attendance reduced recidivism. No randomized clinical trials have been performed that target pretransplantation risk factors in individuals with alcoholic liver disease before or after OLT to improve post-OLT outcomes. Recent research findings suggest that screening can reveal individuals who are vulnerable to alcohol relapse and targeted intervention can prevent their relapse to alcohol. Based on existing addiction treatments (e.g., relapse prevention plan construction), randomized clinical trials tailored to post-OLT patients should be conducted to improve their survival and quality of life. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Quantification of lead and cadmium in poultry and bird game meat by square-wave anodic-stripping voltammetry.

PubMed

Trevisani, M; Cecchini, M; Taffetani, L; Vercellotti, L; Rosmini, R

2011-02-01

A square-wave anodic-stripping voltammetric method for the analysis of lead and cadmium in chicken muscle and liver was developed and validated, and the results of a monitoring study relative to chicken and pigeon meat are reported. The voltammetric method allows the analysis of lead and cadmium at the same time in samples after acid digestion. The use of perchloric acid for digestion and of acetate buffer in the supporting electrolyte are suitable to reduce matrix interferences and obtain limits of quantification which were below 10 ng g⁻¹ for meat and liver samples. The regression between the analytical signal and the concentration of the target analytes in spiked samples and Certified Reference Materials proved to be linear within the 10-100 ng g⁻¹ range for meat and within the 50-500 ng g⁻¹ range for liver. The analytical method was verified using available Certified Reference Materials BCR-184 (cattle meat) and BCR-185R (cattle liver) as well as with spiked chicken samples. Precision (i.e. repeatability and intermediate precision) and accuracy (percentage recovery and bias) were of the order of 0.3-4.5% for both lead and cadmium The level of lead in muscle was in the range between 6.4 and 59.8 ng g⁻¹ in chickens and between 7.9 and 63.6 ng g⁻¹ in farmed pigeons, whereas it was between 8.0 and 84.4 ng g⁻¹ in chicken liver. The cadmium concentration was 0.4-10.4 ng g⁻¹ in chicken muscle, 10.4-90.6 ng g⁻¹ in chicken liver and 2.2-8.0 ng g⁻¹ in farmed pigeons.

Prevalence and Outcome of Nonalcoholic Fatty Liver Disease in Adolescents and Young Adults Undergoing Weight Loss Surgery

PubMed Central

Corey, Kathleen E.; Stanley, Takara L.; Misdraji, Joseph; Scirica, Christina; Pratt, Janey; Hoppin, Alison; Misra, Madhusmita

2014-01-01

We evaluated the prevalence of NAFLD (nonalcoholic fatty liver disease) and NASH (nonalcoholic steatohepatitis) in 27 adolescents referred for weight loss surgery (WLS). On biopsy 18 patients (66.7%) had NAFLD, and of those, 10 patients (37.0%) had NASH and 11 (40.7%) had fibrosis. Insulin, HbA1C and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in patients with NASH than those without NASH. Following WLS, 40% of NASH patients had persistently elevated aminotransferase levels despite weight loss. We found that NASH is underdiagnosed in adolescents referred for WLS and hyperinsulinemia, HOMA-IR and HbA1c can aid in identifying high-risk patients. PMID:24677740

Approach to the patient with abnormal liver tests.

PubMed

Mahl, T C

1998-01-01

Patients with abnormal liver blood tests are frequently encountered by primary care practitioners. An understanding of the cellular implications of these abnormalities is helpful in determining the etiology of liver injury. Elevated serum aminotransferases suggest injury of hepatocytes. Elevations in alkaline phosphatase suggest injury to any part of the biliary tree. Neither of these enzymes measures liver function. Serum bilirubin and albumin levels, as well as prothrombin time, do measure function and can be used in conjunction with the physical examination and the specific etiology of the patient's disorder to determine a patient's prognosis. Many diverse disorders result in similar biochemical patterns of liver injury. The history, physical examination, and use of specific disease markers (hepatitis serology, autoimmune markers, and so forth) help to narrow the differential diagnosis. The definitive diagnosis of all liver diseases usually rests on histology: the liver biopsy is the gold standard. With the advent of treatments for liver disease, identifying and accurately diagnosing patients with liver disorders will result in improved quality of life and survival.

Magnetic resonance imaging measurements of organs within the coelomic cavity of red-eared sliders (Trachemys scripta elegans), yellow-bellied sliders (Trachemys scripta scripta), Coastal plain cooters (Pseudemys concinna floridana), and hieroglyphic river cooters (Pseudemys concinna hieroglyphica).

PubMed

Mathes, Karina A; Schnack, Marcus; Rohn, Karl; Fehr, Michael

2017-12-01

OBJECTIVE To determine anatomic reference points for 4 turtle species and to evaluate data on relative anatomic dimensions, signal intensities (SIs), and position of selected organs within the coelomic cavity by use of MRI. ANIMALS 3 turtle cadavers (1 red-eared slider [Trachemys scripta elegans], 1 yellow-bellied slider [Trachemys scripta scripta], and 1 Coastal plain cooter [Pseudemys concinna floridana]) and 63 live adult turtles (30 red-eared sliders, 20 yellow-bellied sliders, 5 Coastal plain cooters, and 8 hieroglyphic river cooters [Pseudemys concinna hieroglyphica]). PROCEDURES MRI and necropsy were performed on the 3 turtle cadavers. Physical examination, hematologic evaluation, and whole-body radiography were performed on the 63 live turtles. Turtles were sedated, and MRI in transverse, sagittal, and dorsal planes was used to measure organ dimensions, position within the coelomic cavity, and SIs. Body positioning after sedation was standardized with the head, neck, limbs, and tail positioned in maximum extension. RESULTS Measurements of the heart, liver, gallbladder, and kidneys in sagittal, transverse, and dorsal planes; relative position of those organs within the coelom; and SIs of the kidneys and liver were obtained with MRI and provided anatomic data for these 4 turtle species. CONCLUSIONS AND CLINICAL RELEVANCE MRI was a valuable tool for determining the position, dimensions, and SIs of selected organs. Measurement of organs in freshwater chelonians was achievable with MRI. Further studies are needed to establish reference values for anatomic structures in turtles. Results reported here may serve as guidelines and aid in clinical interpretation of MRI images for these 4 species.

Accuracy of apparent diffusion coefficient value measurement on PACS workstation: A comparative analysis.

PubMed

El Kady, Reem M; Choudhary, Arabinda Kumar; Tappouni, Rafel

2011-03-01

The purpose of this article is to evaluate the accuracy of apparent diffusion coefficient (ADC) measurements made with a PACS workstation compared with measurements made with a dedicated workstation, which is currently considered the reference standard. A retrospective review was performed in liver lesions from 79 patients using three MRI platforms. The final diagnosis was established by liver biopsy in 31 patients and by dynamic MRI and follow-up, both clinical and radiologic as indicated, in 48 patients. Each lesion that was clearly demonstrable on the ADC map was measured with a commercial dedicated postprocessing workstation and again with a PACS system. A two-sample t test was used to determine the statistically significant differences between the two ADC measurements. A total of 79 patients with 120 liver lesions were included. ADC values measured on the workstation were 0.4-4.38 × 10(-3) mm(2)/s. The ADC values measured on the PACS were 0.42-4.35 × 10(-3) mm(2)/s. The T value was -1.113, with 119 degrees of freedom, and the significance level was 0.268, which implies no significant difference between the two different measuring systems for all pathologic abnormalities and MRI scanners used. ADC values measured on a routine PACS workstation are as accurate as the values obtained on a dedicated specialized workstation. ADC value measurement on the routine PACS will save time and lead to increased utilization, which, in turn, will lead to an improved understanding of the different disease processes and their clinical management.

Changes in plasma chemistry after drug-induced liver disease or muscle necrosis in racing pigeons (Columba livia domestica).

PubMed

Lumeij, J T; Meidam, M; Wolfswinkel, J; Van der Hage, M H; Dorrestein, G M

1988-01-01

Changes in plasma variables as a result of liver damage induced by ethylene glycol (group A) or D-galactosamine (group B) and of muscle damage induced by doxycycline were compared. Plasma bile acid concentration was both a specific and a sensitive indicator of liver disease. Another specific, but less sensitive indicator of liver disease was 7-GT. Plasma AS AT activity was the most sensitive indicator of disease of the liver, but was not specific, since increased ASAT activities were also seen during muscle disease. ALAT activity was slightly more sensitive to liver damage than 7-GT, but was also not specific, being increased also after muscle damage. Plasma GLDH activity was increased only as a result of extensive liver necrosis. AP activity was of no value for detecting liver disease in the pigeon. CK activity was specific for muscle injury, though the activities of ALAT, ASAT and LD were also increased. Because of its long elimination half-life, increased ALAT activity persisted for 9 days after muscle damage, whereas CK activity returned to reference values within 3 days. LDH was a poor indicator of damage to liver and muscle, despite its relatively high tissue concentrations in both tissues. The rapid disappearance rate of LDH from plasma probably explains this observation.

Single-Center Experience Using Marginal Liver Grafts in Korea.

PubMed

Park, P-J; Yu, Y-D; Yoon, Y-I; Kim, S-R; Kim, D-S

2018-05-01

Liver transplantation (LT) is an established therapeutic modality for patients with end-stage liver disease. The use of marginal donors has become more common worldwide due to the sharp increase in recipients, with a consequent shortage of suitable organs. We analyzed our single-center experience over the last 8 years in LT to evaluate the outcomes of using so-called "marginal donors." We retrospectively analyzed the database of all LTs performed at our institution from 2009 to 2017. Only patients undergoing deceased-donor LTs were analyzed. Marginal grafts were defined as livers from donors >60 years of age, livers from donors with serum sodium levels >155 mEq, graft steatosis >30%, livers with cold ischemia time ≥12 hours, livers from donors who were hepatitis B or C virus positive, livers recovered from donation after cardiac death, and livers split between 2 recipients. Patients receiving marginal grafts (marginal group) were compared with patients receiving standard grafts (standard group). A total of 106 patients underwent deceased-donor LT. There were 55 patients in the standard group and 51 patients in the marginal group. There were no significant differences in terms of age, sex, Model for End-Stage Liver Disease score, underlying liver disease, presence of hepatocellular carcinoma, and hospital stay between the 2 groups. Although the incidence of acute cellular rejection, cytomegalovirus infection, and postoperative complications was similar between the 2 groups, the incidence of early allograft dysfunction was higher in the marginal group. With a median follow-up of 26 months, the 1-, 3-, and 5-year overall and graft (death-censored) survivals in the marginal group were 85.5%, 75%, and 69.2% and 85.9%, 83.6%, and 77.2%, respectively. Patient overall survival and graft survival (death-censored) were significantly lower in the marginal group (P = .023 and P = .048, respectively). On multivariate analysis, receiving a marginal graft (hazard ratio [HR], 4.862 [95% confidence interval (CI), 1.233-19.171]; P = .024) and occurrence of postoperative complications (HR, 4.547 [95% CI, 1.279-16.168]; P = .019) were significantly associated with worse patient overall survival. Also, when factors associated with marginal graft were analyzed separately, graft steatosis >30% was independently associated with survival (HR, 5.947 [95% CI, 1.481-23.886]; P = .012). Patients receiving marginal grafts showed lower but acceptable overall survival and graft survival. However, because graft steatosis >30% was independently associated with worse survival, caution must be exercised when using this type of marginal graft by weighing the risk and benefits. Copyright © 2018 Elsevier Inc. All rights reserved.

Serious gaming for orthotopic liver transplant anesthesiology: A randomized control trial.

PubMed

Katz, Daniel; Zerillo, Jeron; Kim, Sang; Hill, Bryan; Wang, Ryan; Goldberg, Andrew; DeMaria, Samuel

2017-04-01

Anesthetic management of orthotopic liver transplantation (OLT) is complex. Given the unequal distributions of liver transplant surgeries performed at different centers, anesthesiology providers receive relatively uneven OLT training and exposure. One well-suited modality for OLT training is the "serious game," an interactive application created for the purpose of imparting knowledge or skills, while leveraging the self-motivating elements of video games. We therefore developed a serious game designed to teach best practices for the anesthetic management of a standard OLT and determined if the game would improve resident performance in a simulated OLT. Forty-four residents on the liver transplant rotation were randomized to either the gaming group (GG) or the control group (CG) prior to their introductory simulation. Both groups were given access to the same educational materials and literature during their rotation, but the GG also had access to the OLT Trainer. Performance on the simulations were recorded on a standardized grading rubric. Both groups experienced an increase in score relative to baseline that was statistically significant at every stage. The improvements in scores were greater for the GG participants than the CG participants. Overall score improvement between the GG and CG (mean [standard deviation]) was statistically significant (GG, 7.95 [3.65]; CG, 4.8 [4.48]; P = 0.02), as were scores for preoperative assessment (GG, 2.67 [2.09]; CG, 1.17 [1.43]; P = 0.01) and anhepatic phase (GG, 1.62 [1.01]; CG, 0.75 [1.28]; P = 0.02). Of the residents with game access, 81% were "very satisfied" or "satisfied" with the game overall. In conclusion, adding a serious game to an existing educational curriculum for liver transplant anesthesia resulted in significant learning gains for rotating anesthesia residents. The intervention was straightforward to implement and cost-effective. Liver Transplantation 23 430-439 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Effect of Transitioning from Standard Reference Material 2806a to Standard Reference Material 2806b for Light Obscuration Particle Countering

DTIC Science & Technology

2016-04-01

Reference Material 2806b for Light Obscuration Particle Countering April 2016 UNCLASSIFIED UNCLASSIFIED Joel Schmitigal 27809 Standard Form 298 (Rev...Standard Reference Material 2806b for Light Obscuration Particle Countering 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Reference Material 2806a to Standard Reference Material 2806b for Light Obscuration Particle Countering Joel Schmitigal Force Projection

Method optimization for fathead minnow (Pimephales promelas) liver S9 isolation

EPA Science Inventory

Standard protocols have been proposed to assess metabolic stability in rainbow trout liver S9 fractions. Using in vitro substrate depletion assays, in vitro intrinsic clearance rates can be calculated for a variety of study compounds. Existing protocols suggest potential adaptati...

Novel Antibody Targets Glypican-3 in Liver Cancer | Center for Cancer Research

Cancer.gov

New treatments for patients with liver cancer, the third most common cause of cancer-related death, are desperately needed. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and HCC tumors are particularly insensitive to chemotherapy. Surgery is the standard treatment for HCCs caught early, but only about a third of cases are identified at this stage. Antibody therapy offers a potential alternative for treating later-stage tumors.

Phantom Study Investigating the Accuracy of Manual and Automatic Image Fusion with the GE Logiq E9: Implications for use in Percutaneous Liver Interventions.

PubMed

Burgmans, Mark Christiaan; den Harder, J Michiel; Meershoek, Philippa; van den Berg, Nynke S; Chan, Shaun Xavier Ju Min; van Leeuwen, Fijs W B; van Erkel, Arian R

2017-06-01

To determine the accuracy of automatic and manual co-registration methods for image fusion of three-dimensional computed tomography (CT) with real-time ultrasonography (US) for image-guided liver interventions. CT images of a skills phantom with liver lesions were acquired and co-registered to US using GE Logiq E9 navigation software. Manual co-registration was compared to automatic and semiautomatic co-registration using an active tracker. Also, manual point registration was compared to plane registration with and without an additional translation point. Finally, comparison was made between manual and automatic selection of reference points. In each experiment, accuracy of the co-registration method was determined by measurement of the residual displacement in phantom lesions by two independent observers. Mean displacements for a superficial and deep liver lesion were comparable after manual and semiautomatic co-registration: 2.4 and 2.0 mm versus 2.0 and 2.5 mm, respectively. Both methods were significantly better than automatic co-registration: 5.9 and 5.2 mm residual displacement (p < 0.001; p < 0.01). The accuracy of manual point registration was higher than that of plane registration, the latter being heavily dependent on accurate matching of axial CT and US images by the operator. Automatic reference point selection resulted in significantly lower registration accuracy compared to manual point selection despite lower root-mean-square deviation (RMSD) values. The accuracy of manual and semiautomatic co-registration is better than that of automatic co-registration. For manual co-registration using a plane, choosing the correct plane orientation is an essential first step in the registration process. Automatic reference point selection based on RMSD values is error-prone.

Right hemihepatectomy.

PubMed

Haglund, Ulf H; Norén, Agneta; Urdzik, Jozef; Duraj, Frans F

2008-07-01

A right hemihepatectomy is frequently required for surgical removal of colorectal liver metastases. Today, this procedure can be performed quite safely provided the remaining liver is free from significant disease including steatohepatitis due to prolonged cytostatic treatment. Standard surgical techniques for liver resection are described in surgical textbooks. However, each center has developed its own modifications of important details. In this paper, we describe our technique to resect the right liver lobe using conventional surgical techniques as well as a vascular stapler and an ultrasonic dissector. This technique has proven to be quite safe, and blood loss is most often not significant despite we do not routinely apply the Pringle's manoeuvre during the division of the liver parenchyma.

The liver tissue bank and clinical database in China.

PubMed

Yang, Yuan; Liu, Yi-Min; Wei, Ming-Yue; Wu, Yi-Fei; Gao, Jun-Hui; Liu, Lei; Zhou, Wei-Ping; Wang, Hong-Yang; Wu, Meng-Chao

2010-12-01

To develop a standardized and well-rounded material available for hepatology research, the National Liver Tissue Bank (NLTB) Project began in 2008 in China to make well-characterized and optimally preserved liver tumor tissue and clinical database. From Dec 2008 to Jun 2010, over 3000 individuals have been enrolled as liver tumor donors to the NLTB, including 2317 cases of newly diagnosed hepatocellular carcinoma (HCC) and about 1000 cases of diagnosed benign or malignant liver tumors. The clinical database and sample store can be managed easily and correctly with the data management platform used. We believe that the high-quality samples with detailed information database will become the cornerstone of hepatology research especially in studies exploring the diagnosis and new treatments for HCC and other liver diseases.

The role of ultrasound elastographic techniques in chronic liver disease: current status and future perspectives.

PubMed

Piscaglia, Fabio; Marinelli, Sara; Bota, Simona; Serra, Carla; Venerandi, Laura; Leoni, Simona; Salvatore, Veronica

2014-03-01

This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment. The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

PubMed Central

Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

2015-01-01

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations. PMID:25234328

Hepatoprotective activity of petroleum ether, diethyl ether, and methanol extract of Scoparia dulcis L. against CCl4-induced acute liver injury in mice.

PubMed

Praveen, T K; Dharmaraj, S; Bajaj, Jitendra; Dhanabal, S P; Manimaran, S; Nanjan, M J; Razdan, Rema

2009-06-01

The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM) extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. The PDM extract (50, 200, and 800 mg/kg, p.o.) and standard, silymarin (100 mg/kg, p.o) were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05) and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.). In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 +/- 1.0 mug/ml). The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents.

Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection.

PubMed

Cieslak, Kasia P; Bennink, Roelof J; de Graaf, Wilmar; van Lienden, Krijn P; Besselink, Marc G; Busch, Olivier R C; Gouma, Dirk J; van Gulik, Thomas M

2016-09-01

(99m)Tc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated. 163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m(2) were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods. 29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods. Implementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Feasibility study on image guided patient positioning for stereotactic body radiation therapy of liver malignancies guided by liver motion.

PubMed

Heinz, Christian; Gerum, Sabine; Freislederer, Philipp; Ganswindt, Ute; Roeder, Falk; Corradini, Stefanie; Belka, Claus; Niyazi, Maximilian

2016-06-27

Fiducial markers are the superior method to compensate for interfractional motion in liver SBRT. However this method is invasive and thereby limits its application range. In this retrospective study, the compensation method for the interfractional motion using fiducial markers (gold standard) was compared to a new non-invasive approach, which does rely on the organ motion of the liver and the relative tumor position within this volume. We analyzed six patients (3 m, 3f) treated with SBRT in 2014. After fiducial marker implantation, all patients received a treatment CT (free breathing, without abdominal compression) and a 4D-CT (consisting of 10 respiratory phases). For all patients the gross tumor volumes (GTVs), internal target volume (ITV), planning target volume (PTV), internal marker target volumes (IMTVs) and the internal liver target volume (ILTV) were delineated based on the CT and 4D-CT images. CBCT imaging was used for the standard treatment setup based on the fiducial markers. According to the patient coordinates the 3 translational compensation values (t x , t y , t z ) for the interfractional motion were calculated by matching the blurred fiducial markers with the corresponding IMTV structures. 4 observers were requested to recalculate the translational compensation values for each CBCT (31) based on the ILTV structures. The differences of the translational compensation values between the IMTV and ILTV approach were analyzed. The magnitude of the mean absolute 3D registration error with regard to the gold standard overall patients and observers was 0.50 cm ± 0.28 cm. Individual registration errors up to 1.3 cm were observed. There was no significant overall linear correlation between the respiratory motion and the registration error of the ILTV approach. Two different methods to calculate the translational compensation values for interfractional motion in stereotactic liver therapy were evaluated. The registration accuracy of the ILTV approach is mainly limited by the non-rigid behavior of the liver and the individual registration experience of the observer. The ILTV approach lacks the accuracy that would be desired for stereotactic radiotherapy of the liver.

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

PubMed

Ruefer, Axel; Bapst, Christine; Benz, Rudolf; Bremerich, Jens; Cantoni, Nathan; Infanti, Laura; Samii, Kaveh; Schmid, Mathias; Vallée, Jean-Paul

2017-11-09

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.

Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B.

PubMed

Enomoto, Masaru; Morikawa, Hiroyasu; Tamori, Akihiro; Kawada, Norifumi

2014-09-14

Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necroinflammatory activity, and staging fibrosis. However, liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications, including death. Several noninvasive evaluations have been introduced for the assessment of liver fibrosis: serum biomarkers, combined indices or scores, and imaging techniques including transient elastography, acoustic radiation force impulse, real-time tissue elastography, and magnetic resonance elastography. Here, we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C, and later in those with chronic hepatitis B. The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease.

Hepatosplenic Cat-Scratch Disease in Children and the Positive Contribution of 18F-FDG Imaging.

PubMed

Kraft, Karianne E; Doedens, Rienus A; Slart, Riemer H J A

2015-09-01

Two patients were referred to our hospital because of suspected malignancy. In patient 1, a 4-year-old boy, a F-FDG PET scan showed an enlarged liver with multiple FDG-positive nodular lesions. In patient 2, a 16-year-old boy, a FDG PET-(low-dose) CT showed an enlarged liver and spleen with multiple nodular lesions and a solitary hypodense nodule adjacent to the pancreatic head. The lesions were thought to originate from infectious disease or lymphoma. Polymeric chain reaction (PCR) on a liver biopsy was positive for Bartonella henselae. Both patients were treated with antibiotics and recovered completely.

Mortality among workers monitored for radiation exposure at the French nuclear fuel company.

PubMed

Metz-Flamant, C; Rogel, A; Caër, S; Samson, E; Laurier, D; Acker, A; Tirmarche, M

2009-01-01

A cohort of 9,285 nuclear workers employed at the French company AREVA NC specializing in the nuclear fuel cycle was established. Vital status, causes of death, employment characteristics and annual exposure to ionizing radiation were reconstructed for each individual over the time period 1977-2004. Standardized mortality ratios (SMRs) were computed using national mortality rates as an external reference. Tests for trends in mortality with duration of employment and cumulative external dose were performed. The all-cause and all-cancer mortality was significantly lower than expected from the French population. No significant excess among cancer sites studied was observed. Significant positive trends with cumulative dose were observed for colon and liver cancer and for respiratory diseases. Isolated significant trends should be carefully interpreted and considered in line with the large number of trend tests performed.

Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

PubMed Central

2013-01-01

Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

PubMed

Alvarez, Daniel; Orozco, Federico; Mella, José María; Anders, Maria; Antinucci, Florencia; Mastai, Ricardo

2015-01-01

The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. We evaluated the effect of food intake on LS in patients with different degrees of liver disease. We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Liver regenerative medicine: advances and challenges.

PubMed

Chistiakov, Dimitry A

2012-01-01

Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research.

PubMed

Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

2018-02-27

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

Major Challenges Limiting Liver Transplantation in the United States

PubMed Central

Wertheim, Jason A.; Petrowsky, Henrik; Saab, Sammy; Kupiec-Weglinski, Jerzy W.; Busuttil, Ronald W.

2011-01-01

Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: 1) the need for an expanded number of useable donor organs, 2) the need for improved therapies to treat recurrent hepatitis C after transplantation and 3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma. PMID:21672146

Preoperative evaluation of hepatic arterial and portal venous anatomy using the time resolved echo-shared MR angiographic technique in living liver donors.

PubMed

Lee, Min Woo; Lee, Jeong Min; Lee, Jae Young; Kim, Se Hyung; Park, Eun-Ah; Han, Joon Koo; Choi, Jin-Young; Kim, Young Jun; Suh, Kyung-Suk; Choi, Byung Ihn

2007-04-01

The purpose of this study was to determine whether MR angiography utilizing the time resolved echo-shared angiographic technique (TREAT) can provide an effective assessment of the hepatic artery (HA) and portal vein (PV) in living donor candidates. MR angiography (MRA)was performed in 27 patients (23 men and 4 women; mean age, 31 years) by using TREAT. Two blinded radiologists evaluated HA anatomy, origin of segment IV feeding artery and PV anatomy in consensus. Qualitative evaluations of MRA images were performed using the following criteria: (a) overall image quality, (b) presence of artifacts, and (c) degree of venous contamination of the arterial phase. Using intraoperative findings as a standard of reference, the accuracy for the HA anatomy, origin of segment IV feeding artery and PV anatomy on TREAT-MRA were 93% (25/27), 85% (23/27), and 96% (26/27), respectively. Overall image qualities were as follows: excellent (n=22, 81%), good (n=4, 15%), and fair (n=1, 4%). Significant artifacts or venous contamination of the arterial phase images was not noted in any patient. TREAT-MRA can provide a complete evaluation of HA and PV anatomy during preoperative evaluation of living liver donors. Furthermore, it provides a more detailed anatomy of the HA without venous contamination.

A first reported case of metastatic anorectal amelanotic melanoma with a marked response to anti-PD-1 antibody nivolumab: A case report.

PubMed

Tokuhara, Katsuji; Nakatani, Kazuyoshi; Tanimura, Hirotsugu; Yoshioka, Kazuhiko; Kiyohara, Takahiro; Kon, Masanori

2017-01-01

Anorectal amelanotic melanoma (AAMM) is a rare disease with poor prognosis. A standard treatment strategy for AAMM has not been established. We report a case of successful treatment of AAMM with nivolumab. A 67-year-old man was referred for colonoscopy which revealed type I tumor in the rectum. AAMM was diagnosed with immunostaining histopathological biopsy findings. Enhanced computed tomography (ECT) revealed the rectal tumor without distant organ metastasis. We performed laparoscopy-assisted abdominoperineal resection. ECT at three months after surgery revealed liver metastases and right ischial bone metastasis. Although we had started dacarbazine monotherapy, black spots that were suspicious of skin metastases had appeared on systemic skin. Therefore, we started nivolumab therapy. ECT at 3 months after initiation of nivolumab showed shrinkage of liver metastasis. We have continued strict follow-up every 2 months and checked no oncologic progression at 17 months after initiation of nivolumab. The anti-PD-1 antibody have improved prognosis of malignant melanoma. However, there are no reports of nivolumab for treatment of AAMM. Our patient is the first reported case of AAMM treated with nivolumab. We consider that nivolumab will be effective for non-cutaneous malignant melanoma. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Liver Full Reference Set Application :Timothy Block - Drexel Univ (2010) — EDRN Public Portal

Cancer.gov

The goal of this application is to determine if the levels of serum GP73 and fucosylated kininogen/acute phase proteins can be used to detect hepatocellular carcinoma (HCC) in the background of liver cirrhosis. The use of the validation set would allow us to directly compare GP73 and fucosylated markers against AFP, AFP-L3 and DCP as well as test them in combination with these markers

Remedial Investigation Badger Army Ammunition Plant, Baraboo, Wisconsin. Volume 7. Appendices M Through R

DTIC Science & Technology

1991-01-01

cell transformation test with rat embryo cells (Price et al., 1978). An isomer, 1,1,2-trichloroethane, is carcinogenic in mice, inducing liver cancer and...pheochromocytomas in both sexes. Dichloroethanes, tetrachloroethanes and hexachloroethanes also produced liver cancer in mice and other types of...at this time, so the recommended criteria represents an E-6 estimated incrnental increase of cancer risk over a lifetime. Reference - 45 FR 79318 (11

Liver Rapid Reference Set Application: Timothy Block - Drexel Univ (2008) — EDRN Public Portal

Cancer.gov

The goal of this application is to determine if the levels of serum GP73 and fucosylated kininogen/acute phase proteins can be used to detect hepatocellular carcinoma (HCC) in the background of liver cirrhosis. The use of the validation set would allow us to directly compare GP73 and fucosylated markers against AFP, AFP-L3 and DCP as well as test them in combination with these markers

Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

PubMed

Bulla, O; Poncet, A; Alberio, L; Asmis, L M; Gähler, A; Graf, L; Nagler, M; Studt, J-D; Tsakiris, D A; Fontana, P

2017-07-01

Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard. When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard. © 2017 John Wiley & Sons Ltd.

Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

PubMed

Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

2014-05-01

Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). Copyright © 2013 John Wiley & Sons, Ltd.

[Research advances in indices and methods for nutritional status evaluation in patients with liver cirrhosis].

PubMed

Li, H; Zhang, L

2017-03-20

In recent years, malnutrition in patients with liver cirrhosis has been taken more and more seriously in clinical physicians, and patients' nutritional status is closely associated with prognosis. At present, there are many methods for the evaluation of nutritional status in patients with liver cirrhosis, but there are still no unified standards. This article reviews the common evaluation indices and methods used in clinical practice in China and foreign countries, in order to provide a basis for accurately evaluating nutritional status and guiding nutritional therapy in patients with liver cirrhosis.

Liver Metabolite Concentrations Measured with 1H MR Spectroscopy

PubMed Central

Pettigrew, Roderic I.; Gharib, Ahmed M.

2012-01-01

Purpose: To determine the feasibility of measuring choline and glycogen concentrations in normal human liver in vivo with proton (hydrogen 1 [1H]) magnetic resonance (MR) spectroscopy. Materials and Methods: Signed consent to participate in an institutional review board–approved and HIPAA-compliant study was obtained from 46 subjects (mean age, 46 years ± 17 [standard deviation]; 24 women) consecutively recruited during 285 days. Navigator-gated MR images were used to select 8-mL volumes for point-resolved spectroscopy (PRESS) with a 35-msec echo time. Line widths were minimized with fast breath-hold B0 field mapping and further manual shimming. Navigator-gated spectra were recorded with and without water suppression to determine metabolite concentrations with water signals as an internal reference. In three subjects, echo time was varied to determine the glycogen and choline T2. Linear regression analysis was used to examine relations between choline, hepatic lipid content, body mass index, glycogen content, and age. Results: Choline concentrations could be determined in 46 of 48 studies and was found to be 8.6 mmol per kilogram of wet weight ± 3.1 (range, 3.8–17.6; n = 44). Twenty-seven spectra in 25 individuals with narrow line widths and low lipid content were adequate for quantitation of glycogen. The glycogen (glucosyl unit) concentration was 38.1 mmol/kg wet weight ± 14.4. The T2 of combined glycogen peaks in the liver of three subjects was 36 msec ± 8. Choline levels showed a weak but significant correlation with glycogen (r2 = 0.15; P < .05) but not with lipid content. Conclusion: Navigator-gated and gradient-echo shimmed PRESS 1H MR spectroscopy may allow quantification of liver metabolites that are important for understanding and identifying disorders of glucose and lipid metabolism. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112344/-/DC1 PMID:22891360

Sonographic Assessment of the Normal Dimensions of Liver, Spleen, and Kidney in Healthy Children at Tertiary Care Hospital.

PubMed

Thapa, N B; Shah, S; Pradhan, A; Rijal, K; Pradhan, A; Basnet, S

2015-01-01

Background Ultrasonography is one of the most common imaging modality to measure dimensions of visceral organs in children. However, the normal limit of size of visceral organs according to age and body habitus has not been specified in the standard textbooks. This might result in under detection of organomegaly in pediatrics population. Objective The objective of this study was to determine the normal range of dimensions for the liver, spleen, and kidney in healthy children. Method This is prospective cross-sectional, hospital-based study done at Tertiary-care teaching hospital. Participants included 272 pediatric subjects (152 male and 120 female) with normal physical or sonographic findings who were examined because of problems unrelated to the measured organs. The subjects were one month to 15 year (180 months) old. All measured organs were sonographically normal. Relationships of the dimensions of these organs with sex, age, body weight and height were investigated. Limits of normal dimensions of these organs were defined. Result Normal length of liver, kidneys and spleen were obtained sonographically for 272 children (152 male [55.9%] and 120 female [44.1%]) in the age group from 1 months to 15 (180 months) years. The mean age was 45.78 months (SD, 44.73). The measured dimensions of all these organs showed highest correlation with height and age so the descriptive analysis of the organ dimensions (mean, minimum, and maximum values, SD and 5th and 95th percentiles) were expressed in 10 age groups along with height range of the included children. The mean length of right kidney was shorter than the left kidney length, and the difference was statistically significant (p = 0.001). Conclusion This study provides practical and comprehensive guide to the normal visceral organ dimension in pediatric population. The normal range limit of the liver, spleen, and kidney determined in this study could be used as a reference in daily practice in local radiology clinics.

Survival Outcomes for Patients With Indeterminate 18FDG-PET Scan for Extrahepatic Disease Before Liver Resection for Metastatic Colorectal Cancer: A Retrospective Cohort Study Using a Prospectively Maintained Database to Analyze Survival Outcomes for Patients With Indeterminate Extrahepatic Disease on 18FDG-PET Scan Before Liver Resection for Metastatic Colorectal Cancer.

PubMed

Wong, Geoffrey Yuet Mun; Kumar, Rajiv; Beeke, Carol; Ullah, Shahid; Chen, John; Karapetis, Christos; Price, Timothy; Padbury, Rob

2018-05-01

The aim of this study was to evaluate overall survival (OS) and cancer recurrence for patients with indeterminate positron emission tomography (PET) scan for extrahepatic disease (EHD) before liver resection (LR) for colorectal liver metastases (CLMs). Indeterminate EHD as determined by PET imaging indicates a probability of extrahepatic malignancy and potentially excludes patients from undergoing LR for CLM. In a retrospective analysis of prospectively collected data from February 2006 to December 2014, OS for patients with indeterminate EHD on FDG-PET scan before LR for CLM was performed using standard survival analysis methods, including Kaplan-Meier estimator and Cox proportional hazard models for multivariate analyses. Postoperative imaging was used as reference to evaluate the association between indeterminate EHD and recurrence. Of 267 patients with PET scans before LR, 197 patients had no EHD and 70 patients had indeterminate EHD. Median follow-up was 33 months. The estimated 5-year OS was 60.8% versus 59.4% for indeterminate and absent EHD, respectively (P = 0.625). Disease-free survival was comparable between both groups (P = 0.975) and overall recurrence was 57.1% and 59.5% for indeterminate and absent EHD, respectively (P = 0.742). About 16.9% of recurrence was associated with the site of indeterminate EHD, with 80% of associated recurrence occurring in the thorax. The site of indeterminate EHD appears to have a predictive value for recurrence, with indeterminate EHD in the thorax having a higher probability of malignancy. The evidence in this report supports the critical evaluation of PET scan results and that patients are not denied potential curative LR unless the evidence for unresectable EHD is certain.

A multicenter study on PIVKA reference interval of healthy population and establishment of PIVKA cutoff value for hepatocellular carcinoma diagnosis in China.

PubMed

Qin, X; Tang, G; Gao, R; Guo, Z; Liu, Z; Yu, S; Chen, M; Tao, Z; Li, S; Liu, M; Wang, L; Hou, L; Xia, L; Cheng, X; Han, J; Qiu, L

2017-08-01

The aim of this study was to investigate the reference interval of protein-induced vitamin K absence or antagonist-II (PIVKA-II) in China population and to evaluate its medical decision level for hepatocellular carcinoma (HCC) diagnosis. To determine the reference range for Chinese individuals, a total of 855 healthy subjects in five typical regions of China were enrolled in this study to obtain a 95% reference interval. In a case-control study which recruited the subjects diagnosed with HCC, metastatic liver cancer, bile duct cancer, hepatitis, cirrhosis, other benign liver diseases and the subjects administrated anticoagulant, receiver operating characteristic analysis was used to determine PIVKA-II cutoff value for a medical decision. The concentration of PIVKA-II had no relationship with age or gender and that region was a significant factor associated with the level of PIVKA-II. The 95% reference interval determined in this study for PIVKA-II in Chinese healthy individuals was 28 mAU/mL, and the cutoff value which to distinguish patients with HCC from disease control groups is 36.5 mAU/mL. In clinical applications, it is recommended that each laboratory chooses their own reference interval based on the regional population study or cutoff value for disease diagnosis. © 2017 John Wiley & Sons Ltd.

Portal inflow and pressure changes in right liver living donor liver transplantation including the middle hepatic vein.

PubMed

Chan, See Ching; Lo, Chung Mau; Ng, Kelvin K C; Ng, Irene O L; Yong, Boon Hun; Fan, Sheung Tat

2011-02-01

The middle hepatic vein may be included in right liver living donor liver transplantation (LDLT) to optimize hepatic venous outflow. We studied the graft's ability to relieve portal hypertension and accommodate portal hyperperfusion with portal manometry and ultrasonic flowmetry. Surgical outcomes with respect to portal hemodynamometry were also investigated. The ages of the recipients and donors for 46 consecutive LDLT procedures were 50 (range, 16-66 years) and 31 years (range, 18-54 years), respectively. The graft to standard liver volume ratio was 47.4% (range, 32.4%-69.0%). The hospital mortality rate was 4.4% as 2 recipients died from a subarachnoid hemorrhage and sepsis. The portal pressure dropped by 8 mm Hg (range, -7 to 19 mm Hg) from 23 (range, 8-37 mm Hg) to 14 mm Hg (range, 10-26 mm Hg) after graft implantation. The portal inflow positively correlated with the portal pressure before native liver hepatectomy (R(2) = 0.305, P = 0.001) and not with the graft size. The portal inflow increased from 81 mL/minute/100 g (range, 35-210 mL/minute/100 g) before donor right hepatectomy to 318 mL/minute/100 g (range, 102-754 mL/minute/100 g) after graft implantation. The graft portal inflow had a positive linear correlation with the recipient portal pressure before native liver total hepatectomy (R(2) = 0.261, P = 0.001) but not after graft implantation, and it had a negative correlation with the graft to standard liver volume ratio (R(2) = 0.247, P = 0.001). Only 1 of the graft biopsies showed moderate sinusoidal congestion. Twelve recipients had Clavien grade 2+ complications that were not related to the portal inflow and pressure or graft size. Right liver LDLT including the middle hepatic vein effectively lowered the recipient portal pressure by allowing unimpeded venous outflow. Copyright © 2011 American Association for the Study of Liver Diseases.

Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia—Important Lessons From the First 12 Cases

PubMed Central

Watson, Christopher J.E.; Kosmoliaptsis, Vasilis; Randle, Lucy V.; Gimson, Alexander E.; Brais, Rebecca; Klinck, John R.; Hamed, Mazin; Tsyben, Anastasia; Butler, Andrew J.

2017-01-01

Background A program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia. Methods Declined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate. Results Twelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP. Conclusions Normothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes. PMID:28437389

Fat Quantification in the Abdomen.

PubMed

Hong, Cheng William; Fazeli Dehkordy, Soudabeh; Hooker, Jonathan C; Hamilton, Gavin; Sirlin, Claude B

2017-12-01

Fatty liver disease is characterized histologically by hepatic steatosis, the abnormal accumulation of lipid in hepatocytes. It is classified into alcoholic fatty liver disease and nonalcoholic fatty liver disease, and is an increasingly important cause of chronic liver disease and cirrhosis. Assessing the severity of hepatic steatosis in these conditions is important for diagnostic and prognostic purposes, as hepatic steatosis is potentially reversible if diagnosed early. The criterion standard for assessing hepatic steatosis is liver biopsy, which is limited by sampling error, its invasive nature, and associated morbidity. As such, noninvasive imaging-based methods of assessing hepatic steatosis are needed. Ultrasound and computed tomography are able to suggest the presence of hepatic steatosis based on imaging features, but are unable to accurately quantify hepatic fat content. Since Dixon's seminal work in 1984, magnetic resonance imaging has been used to compute the signal fat fraction from chemical shift-encoded imaging, commonly implemented as out-of-phase and in-phase imaging. However, signal fat fraction is confounded by several factors that limit its accuracy and reproducibility. Recently, advanced chemical shift-encoded magnetic resonance imaging methods have been developed that address these confounders and are able to measure the proton density fat fraction, a standardized, accurate, and reproducible biomarker of fat content. The use of these methods in the liver, as well as in other abdominal organs such as the pancreas, adrenal glands, and adipose tissue will be discussed in this review.

An extra virgin olive oil rich diet intervention ameliorates the nonalcoholic steatohepatitis induced by a high-fat "Western-type" diet in mice.

PubMed

Jurado-Ruiz, Enrique; Varela, Lourdes M; Luque, Amparo; Berná, Genoveva; Cahuana, Gladys; Martinez-Force, Enrique; Gallego-Durán, Rocío; Soria, Bernat; de Roos, Baukje; Romero Gómez, Manuel; Martín, Franz

2017-03-01

We evaluated the protective effect of extra virgin olive oil (EVOO) in high-fat diets (HFDs) on the inflammatory response and liver damage in a nonalcoholic fatty liver disease (NAFLD) mouse model. C57BL/6J mice were fed a standard diet or a lard-based HFD (HFD-L) for 12 wk to develop NAFLD. HFD-fed mice were then divided into four groups and fed for 24 wk with the following: HFD-L, HFD-EVOO, HFD based on phenolics-rich EVOO, and reversion (standard diet). HFD-L-induced metabolic disorders were alleviated by replacement of lard with EVOO. EVOO diets improved plasma lipid profile and reduced body weight, plasma and epididymal fat INF-γ, IL-6 and leptin levels, and macrophage infiltration. Moreover, NAFLD activity scores were reduced. The liver lipid composition showed an increase in MUFAs, especially oleic acid, and a decrease in saturated fatty acids. Hepatic adiponutrin and Cd36 gene expression was upregulated in the EVOO groups. Liver ingenuity pathway analysis revealed in EVOO groups regulation of proteins involved in lipid metabolism, small molecule biochemistry, gastrointestinal disease, and liver regeneration. Dietary EVOO could repair HFD-induced hepatic damage, possibly via an anti-inflammatory effect in adipose tissue and modifications in the liver lipid composition and signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cirrhosis and autoimmune liver disease: Current understanding

PubMed Central

Liberal, Rodrigo; Grant, Charlotte R

2016-01-01

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

PubMed

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R; Partovi, Nilufar; Yoshida, Eric M

2016-09-28

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.

Susceptibility of human liver cells to porcine endogenous retrovirus.

PubMed

Lin, Xinzi; Qi, Lin; Li, Zhiguo; Chi, Hao; Lin, Wanjun; Wang, Yan; Jiang, Zesheng; Pan, Mingxin; Gao, Yi

2013-12-01

The risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. Porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. We investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. The supernatant from a porcine kidney cell line was added to human liver cells, including a normal hepatocyte cell line (HL-7702 cells), primary hepatocytes (Phh cells), and a liver stellate cell line (Lx-2 cells), and to human embryonic kidney cells as a reference control. Expression of the porcine endogenous retrovirus antigen p15E in the human cells was evaluated with polymerase chain reaction, reverse transcription-polymerase chain reaction, and Western blot. The porcine endogenous retrovirus antigen p15E was not expressed in any human liver cells (HL-7702, Phh, or Lx-2 cells) that had been exposed to supernatants from porcine kidney cell lines. Porcine endogenous retrovirus-specific fragments were amplified in human kidney cells. Human liver cells tested were not susceptible to infection by porcine endogenous retrovirus. Therefore, not all human cells are susceptible to porcine endogenous retrovirus.

Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

PubMed

Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

2013-06-01

In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study provided proof of principle that our simplified ED (18)F-FDG PET/CT protocol includes endpoints that effectively detect HCC hypervascularization; this finding suggests that the protocol can be used routinely.

Liver X receptor alpha regulates fatty acid synthase expression in chicken.

PubMed

Demeure, O; Duby, C; Desert, C; Assaf, S; Hazard, D; Guillou, H; Lagarrigue, S

2009-12-01

Liver X receptor alpha (LXRalpha), also referred to as nuclear receptor subfamily 1, group H, member 3 is a member of the nuclear hormone receptor superfamily, and has recently been shown to act as a master transcription factor governing hepatic lipogenesis in mammals. Liver X receptor alpha directly regulates both the expression of other lipogenic transcription factors and the expression of lipogenic enzymes, thereby enhancing hepatic fatty acid synthesis (FASN). In birds, like in humans, fatty acid synthesis primarily occurs in the liver. Whether LXRalpha is involved in hepatic regulation of lipogenic genes remained to be investigated in this species. Here we show that fatty acid synthase and the expression of other lipogenic genes (sterol regulatory element binding protein 1 and steroyl coenzyme A desaturase 1) are induced in chicken hepatoma cells in response to a pharmacological liver X receptor agonist, T0901317. A detailed analysis of the chicken FASN promoter revealed a functional liver X response element. These data define the chicken FASN gene as a direct target of LXRalpha and further expand the role of LXRalpha as a regulator of lipid metabolism in this species.

[Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS].

PubMed

Zhao, Xiao-mei; Liu, Xin-ying; Xu, Chang; Ye, Tao; Jin, Cheng; Zhao, Kui-jun; Ma, Zhi-jie; Xiao, Xiao-he

2015-10-01

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.

Alterations of the human gut microbiome in liver cirrhosis.

PubMed

Qin, Nan; Yang, Fengling; Li, Ang; Prifti, Edi; Chen, Yanfei; Shao, Li; Guo, Jing; Le Chatelier, Emmanuelle; Yao, Jian; Wu, Lingjiao; Zhou, Jiawei; Ni, Shujun; Liu, Lin; Pons, Nicolas; Batto, Jean Michel; Kennedy, Sean P; Leonard, Pierre; Yuan, Chunhui; Ding, Wenchao; Chen, Yuanting; Hu, Xinjun; Zheng, Beiwen; Qian, Guirong; Xu, Wei; Ehrlich, S Dusko; Zheng, Shusen; Li, Lanjuan

2014-09-04

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.

Acute liver failure and self-medication.

PubMed

de Oliveira, André Vitorio Câmara; Rocha, Frederico Theobaldo Ramos; Abreu, Sílvio Romero de Oliveira

2014-01-01

Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. To warn about how the practice of self-medication can be responsible for acute liver failure. Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute liver failure [tiab] AND acetaminophen [tiab]; self-medication [tiab] AND acetaminophen [tiab]; acute liver failure [tiab] AND dietary supplements [tiab]; self-medication [tiab] AND liver failure [tiab] and self-medication [tiab] AND green tea [tiab]. In Lilacs and SciELO used the descriptor self medication in Portuguese and Spanish. From total surveyed were selected 27 articles and five sites specifically related to the purpose of this review. Legislation and supervision disabled and information inaccessible to people, favors the emergence of cases of liver failure drug in many countries. In the list of released drugs that deserve more attention and care, are some herbal medicines used for the purpose of weight loss, and acetaminophen. It is recommended that institutes of health intensify supervision and better orient their populations on drug seemingly harmless, limiting the sale of products or requiring a prescription for release them.

Skin and liver diseases induced in flounder (Platichthys flesus) after long-term exposure to contaminated sediments in large-scale mesocosms.

PubMed Central

Vethaak, A D; Jol, J G; Meijboom, A; Eggens, M L; Rheinallt, T; Wester, P W; van de Zande, T; Bergman, A; Dankers, N; Ariese, F; Baan, R A; Everts, J M; Opperhuizen, A; Marquenie, J M

1996-01-01

Disease development in flounder (Platichthys flesus) was studied over a period of 3 years in three large mesocosms (40 m x 40 m x 3 m). Two of the mesocosms contained clean sand and the third, sharing a common water circulation with one of the clean-sand mesocosms, was stocked with contaminated dredged spoil. In this way, one of the clean-sand mesocosms was indirectly polluted via the water phase, and analysis of contaminant concentrations in sediments and flounder tissues showed that it had a status intermediate between the other two. Random samples of the flounder populations from the indirectly polluted and reference mesocosms were examined every 2 months for epidermal diseases (lymphocystis, skin ulcers, fin rot) and then released. In addition, every 6 months, random samples of fish from all three mesocosms were sacrificed for histological and chemical investigation. With regard to the development of epidermal disease, the results showed little difference between the reference mesocosm and the indirectly polluted mesocosm, with the exception that lymphocystis was significantly elevated in the indirectly polluted mesocosm. Although pollution may be a risk factor in the etiology of this disease, such a relationship would probably be obscured under field conditions due to variation arising from other factors. Histopathological analysis of the livers revealed in total four cases of hepatocellular adenoma (1.5% of sampled population) in fish from the polluted mesocosms, the first occurring after 2.5 years of exposure in fish from the indirectly polluted mesocosm. Furthermore, several other liver lesions, including foci of cellular alteration and hydropic vacuolated lesions, developed during the course of the experiment before tumor formation was apparent. Prevalences of these conditions were very much lower in the reference mesocosm than in the two polluted mesocosms. Densities of melanomacrophage centers in the liver showed a similar trend. The findings clearly indicate that long-term exposure to chemically contaminated dredged spoil can induce liver neoplasia and other liver lesions in flounder at contaminant levels comparable to those found in the natural environment. Images Figure 1. Figure 2. Figure 2. Figure 2. Figure 2. Figure 3. Figure 3. Figure 3. Figure 3. Figure 4. Figure 5. Figure 5. Figure 6. Figure 7. PMID:8959412

Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer.

PubMed

Lam, Marnix G E H; Louie, John D; Abdelmaksoud, Mohamed H K; Fisher, George A; Cho-Phan, Cheryl D; Sze, Daniel Y

2014-07-01

To calculate absorbed radiation doses in patients treated with resin microspheres prescribed by the body surface area (BSA) method and to analyze dose-response and toxicity relationships. A retrospective review was performed of 45 patients with colorectal carcinoma metastases who received single-session whole-liver resin microsphere radioembolization. Prescribed treatment activity was calculated using the BSA method. Liver volumes and whole-liver absorbed doses (D(WL)) were calculated. D(WL) was correlated with toxicity and radiographic and biochemical response. The standard BSA-based administered activity (range, 0.85-2.58 GBq) did not correlate with D(WL) (mean, 50.4 Gy; range, 29.8-74.7 Gy; r = -0.037; P = .809) because liver weight was highly variable (mean, 1.89 kg; range, 0.94-3.42 kg) and strongly correlated with D(WL) (r = -0.724; P < .001) but was not accounted for in the BSA method. Patients with larger livers were relatively underdosed, and patients with smaller livers were relatively overdosed. Patients who received D(WL) > 50 Gy experienced more toxicity and adverse events (> grade 2 liver toxicity, 46% vs 17%; P < .05) but also responded better to the treatment than patients who received D(WL)< 50 Gy (disease control, 88% vs 24%; P < .01). Using the standard BSA formula, the administered activity did not correlate with D(WL). Based on this short-term follow-up after salvage therapy in patients with late stage metastatic colorectal carcinoma, dose-response and dose-toxicity relationships support using a protocol based on liver volume rather than BSA to prescribe the administered activity. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

A comparative study of FDG PET/CT and enhanced multi-detector CT for detecting liver metastasis according to the size and location.

PubMed

Park, Jung Mi; Kim, Il Young; Kim, Sang Won; Lee, Sang Mi; Kim, Hyun Gi; Kim, Shin Young; Shin, Hyung Chul

2013-04-01

The aim of this study was to compare the diagnosability between (18)F-fluorodeoxyglucose (FDG) PET/CT and enhanced multi-detector CT (MDCT) for the detection of liver metastasis (LM) according to the size and location in liver and to evaluate standard maximum standardized uptake values (SUVmax) of all liver metastatic lesions. One hundred two consecutive patients with malignancy who underwent both FDG PET/CT and MDCT for LM evaluation were retrospectively reviewed. Among them, 56 patients with LM were enrolled in this study. LM was confirmed by follow-up imaging studies after at least 6 months or by histopathology. FDG PET/CT and MDCT images were visually analyzed using three-point scale by the consensus of two radiologists and two nuclear medicine physicians. The size and location (central vs. sub-capsular) of the all liver lesions were evaluated using MDCT images. Furthermore, SUVmax of all liver lesions on FDG PET/CT images were calculated. A total of 146 liver lesions were detected by FDG PET/CT and MDCT and 142 of the lesions were diagnosed as LM. The detection rates of MDCT and FDG PET/CT for LM by visual analysis were 77 and 78%, respectively. There was no significant difference of detection rate according to the overall location and size of the lesions. However, FDG PET/CT was more sensitive than MDCT for detecting small and sub-capsular LM. The detection rate of FDG PET/CT for LM was 68% by the cutoff SUVmax of 2.7. Although the diagnosabilities of MDCT and FDG PET/CT for detecting LM were comparable, FDG PET/CT is superior to MDCT for detecting small LM located in the sub-capsular portion of liver.

Evaluation of liver fibrosis: "Something old, something new…".

PubMed

Almpanis, Zannis; Demonakou, Maria; Tiniakos, Dina

2016-01-01

Hepatic fibrogenesis may gradually result to cirrhosis due to the accumulation of extracellular matrix components as a response to liver injury. Thus, therapeutic decisions in chronic liver disease, regardless of the cause, should first and foremost be guided by an accurate quantification of hepatic fibrosis. Detection and assessment of the extent of hepatic fibrosis represent a challenge in modern Hepatology. Although traditional histological staging systems remain the "best standard", they are not able to quantify liver fibrosis as a dynamic process and may not accurately substage cirrhosis. This review aims to compare the currently used non-invasive methods of measuring liver fibrosis and provide an update in current tissue-based digital techniques developed for this purpose, that may prove of value in daily clinical practice.

[Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis].

PubMed

Shin, Jung Woo; Park, Neung Hwa

2016-07-25

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis.

 Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis.

PubMed

Díaz, Francia C; Sáez-González, Esteban; Benlloch, Salvador; Álvarez-Sotomayor, Diego; Conde, Isabel; Polo, Begoña; García, María; Rodríguez, María; Prieto, Martín

 Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed. After MARS® procedure, patients' symptoms improved, as well as liver function tests, thus avoiding liver transplantation. Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.

Pictures of focal nodular hyperplasia and hepatocellular adenomas

PubMed Central

Sempoux, Christine; Balabaud, Charles; Bioulac-Sage, Paulette

2014-01-01

This practical atlas aims to help liver and non liver pathologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocellular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for paraffin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glutamine synthase and according to the above results additional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocellular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated. PMID:25232451

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

PubMed

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-10-21

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Effect of Recombinant FVIIA in Hypothermic, Coagulopathic Pigs with Liver Injuries

DTIC Science & Technology

2005-04-01

1󈨊 190 210 230 250 Time (min) United States Army Institute of Surgical Research 33 FIG 5A. Activated Factor FVII (FVIIa) in pig plasma--as measured by...8217X18)F 18) Pre-Dilution Basal Post-Dilution Basal Experimental stage with reference to liver injury FIG 5B. Activated Factor FVII (rFVIIa...the drug, rcombinant activated Factor VII (rFVIIa) on survival, survival time, blood loss, and disseminated intravascular coagulation (DIC) in

For Patients | Center for Cancer Research

Cancer.gov

All patients with primary liver cancer referred to the National Cancer Institute are presented and discussed at a weekly interdisciplinary tumor board to identify the best and most effective treatment option

Ecological comparisons of Lake Erie tributaries with elevated incidence of fish tumors

USGS Publications Warehouse

Smith, Stephen B.; Blouin, Marc A.; Mac, Michael J.

1994-01-01

Ecological comparisons were made between two Lake Erie tributaries (Black and Cuyahoga rivers) with contaminated sediments and elevated rates of tumors in fish populations and a third, relatively unpolluted, reference tributary, the Huron River. Fish populations, benthic invertebrates, and sediments were evaluated in all three Ohio rivers. Community structure analyses indicated similar total densities but lower species diversity for fish and benthic invertebrates in the contaminated rivers when compared with the reference river. Growth rates in fish from the contaminated areas were either similar to or higher than those offish from the reference site. Brown bullhead (Ameiurus nebulosus) from the two contaminated tributaries exhibited 51% (Black River) and 45% (Cuyahoga River) incidence of liver lesions (neoplastic and preneoplastic) as compared with a 4% incidence of liver lesions in brown bullhead from the reference river (Huron River). Incidence of external abnormalities on brown bullhead was 54% (Black River) and 73% (Cuyahoga River) as compared with a 14% incidence on fish from the Huron River. On a regional basis, incidence of external abnormalities on particular benthic fish species may be an effective method to quickly indicate areas for more intensive contaminant studies.

Functional Integrity of the Chimeric (Humanized) Mouse Liver: Enzyme Zonation, Physiologic Spaces, and Hepatic Enzymes and Transporters.

PubMed

Chow, Edwin C Y; Wang, Jason Z Ya; Quach, Holly P; Tang, Hui; Evans, David C; Li, Albert P; Silva, Jose; Pang, K Sandy

2016-09-01

Chimeric mouse liver models are useful in vivo tools for human drug metabolism studies; however, liver integrity and the microcirculation remain largely uninvestigated. Hence, we conducted liver perfusion studies to examine these attributes in FRGN [Fah(-/-), Rag2(-/-), and Il2rg(-/-), NOD strain] livers (control) and chimeric livers repopulated with mouse (mFRGN) or human (hFRGN) hepatocytes. In single-pass perfusion studies (2.5 ml/min), outflow dilution profiles of noneliminated reference indicators ((51)Cr-RBC, (125)I-albumin, (14)C-sucrose, and (3)H-water) revealed preservation of flow-limited distribution and reduced water and albumin spaces in hFRGN livers compared with FRGN livers, a view supported microscopically by tightly packed sinusoids. With prograde and retrograde perfusion of harmol (50 µM) in FRGN livers, an anterior sulfation (Sult1a1) over the posterior distribution of glucuronidation (Ugt1a1) activity was preserved, evidenced by the 42% lower sulfation-to-glucuronidation ratio (HS/HG) and 14% higher harmol extraction ratio (E) upon switching from prograde to retrograde flow. By contrast, zonation was lost in mFRGN and hFRGN livers, with HS/HG and E for both flows remaining unchanged. Remnant mouse genes persisted in hFRGN livers (10%-300% those of FRGN). When hFRGN livers were compared with human liver tissue, higher UGT1A1 and MRP2, lower MRP3, and unchanged SULT1A1 and MRP4 mRNA expression were observed. Total Sult1a1/SULT1A1 protein expression in hFRGN livers was higher than that of FRGN livers, consistent with higher harmol sulfate formation. The composite data on humanized livers suggest a loss of zonation, lack of complete liver humanization, and persistence of murine hepatocyte activities leading to higher sulfation. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Role of histone deacetylases(HDACs) in progression and reversal of liver fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xing; Wu, Xiao-Qin; Xu, Tao

Liver fibrosis refers to a reversible wound healing process response to chronic liver injuries. Activation of hepatic stellate cells (HSCs) is closely correlated with the development of liver fibrosis. Histone deacetylases(HDACs) determine the acetylation levels of core histones to modulate expression of genes. To demonstrate the link between HDACs and liver fibrosis, CCl4-induced mouse liver fibrosis model and its spontaneous reversal model were established. Results of the current study demonstrated that deregulation of liver HDACs may involved in the development of liver fibrosis. Among 11 HDACs tested in our study (Class I, II, and IV HDACs), expression of HDAC2 wasmore » maximally increased in CCl4-induced fibrotic livers but decreased after spontaneous recovery. Moreover, expression of HDAC2 was elevated in human liver fibrotic tissues. In this regard, the potential role of HDAC2 in liver fibrosis was further evaluated. Our results showed that administration of HSC-T6 cells with transforming growth factor-beta1 (TGF-β1) resulted in an increase of HDAC2 protein expression in dose- and time-dependent manners. Moreover, HDAC2 deficiency inhibited HSC-T6 cell proliferation and activation induced by TGF-β1. More importantly, the present study showed HDAC2 may regulate HSCs activation by suppressing expression of Smad7, which is a negative modulator in HSCs activation and liver fibrosis. Collectively, these observations revealed that HDAC2 may play a pivotal role in HSCs activation and liver fibrosis while deregulation of HDACs may serve as a novel mechanism underlying liver fibrosis. - Highlights: • This is the first report to systematically examine expressions of HDACs during liver fibrosis and fibrosis reversal. • Aberrant expression of HDAC2 contributes to the development of liver fibrosis. • Provided important foundation for further liver fibrosis conversion studies.« less

Nontargeted quantitation of lipid classes using hydrophilic interaction liquid chromatography-electrospray ionization mass spectrometry with single internal standard and response factor approach.

PubMed

Cífková, Eva; Holčapek, Michal; Lísa, Miroslav; Ovčačíková, Magdaléna; Lyčka, Antonín; Lynen, Frédéric; Sandra, Pat

2012-11-20

The identification and quantitation of a wide range of lipids in complex biological samples is an essential requirement for the lipidomic studies. High-performance liquid chromatography-mass spectrometry (HPLC/MS) has the highest potential to obtain detailed information on the whole lipidome, but the reliable quantitation of multiple lipid classes is still a challenging task. In this work, we describe a new method for the nontargeted quantitation of polar lipid classes separated by hydrophilic interaction liquid chromatography (HILIC) followed by positive-ion electrospray ionization mass spectrometry (ESI-MS) using a single internal lipid standard to which all class specific response factors (RFs) are related to. The developed method enables the nontargeted quantitation of lipid classes and molecules inside these classes in contrast to the conventional targeted quantitation, which is based on predefined selected reaction monitoring (SRM) transitions for selected lipids only. In the nontargeted quantitation method described here, concentrations of lipid classes are obtained by the peak integration in HILIC chromatograms multiplied by their RFs related to the single internal standard (i.e., sphingosyl PE, d17:1/12:0) used as common reference for all polar lipid classes. The accuracy, reproducibility and robustness of the method have been checked by various means: (1) the comparison with conventional lipidomic quantitation using SRM scans on a triple quadrupole (QqQ) mass analyzer, (2) (31)P nuclear magnetic resonance (NMR) quantitation of the total lipid extract, (3) method robustness test using subsequent measurements by three different persons, (4) method transfer to different HPLC/MS systems using different chromatographic conditions, and (5) comparison with previously published results for identical samples, especially human reference plasma from the National Institute of Standards and Technology (NIST human plasma). Results on human plasma, egg yolk and porcine liver extracts are presented and discussed.

Label-free detection of liver cancer cells by aptamer-based microcantilever biosensor.

PubMed

Chen, Xuejuan; Pan, Yangang; Liu, Huiqing; Bai, Xiaojing; Wang, Nan; Zhang, Bailin

2016-05-15

Liver cancer is one of the most common and highly malignant cancers in the world. There are no effective therapeutic options if an early liver cancer diagnosis is not achieved. In this work, detection of HepG2 cells by label-free microcantilever array aptasensor was developed. The sensing microcantilevers were functionalized by HepG2 cells-specific aptamers. Meanwhile, to eliminate the interferences induced by the environment, the reference microcantilevers were modified with 6-mercapto-1-hexanol self-assembled monolayers. The aptasensor exhibits high specificity over not only human liver normal cells, but also other cancer cells of breast, bladder, and cervix tumors. The linear relation ranges from 1×10(3) to 1×10(5)cells/mL, with a detection limit of 300 cells/mL (S/N=3). Our work provides a simple method for detection of liver cancer cells with advantages in terms of simplicity and stability. Copyright © 2015 Elsevier B.V. All rights reserved.

Polyploidization in liver tissue.

PubMed

Gentric, Géraldine; Desdouets, Chantal

2014-02-01

Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue differentiation and, therefore, possibly a gain of function; alternately, it can be associated with development of disease, such as cancer. Polyploidy can occur because of cell fusion or abnormal cell division (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a common characteristic of the mammalian liver. Polyploidization occurs mainly during liver development, but also in adults with increasing age or because of cellular stress (eg, surgical resection, toxic exposure, or viral infections). This review will explore the mechanisms that lead to the development of polyploid cells, our current state of understanding of how polyploidization is regulated during liver growth, and its consequence on liver function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Quantification of liver fat with respiratory-gated quantitative chemical shift encoded MRI.

PubMed

Motosugi, Utaroh; Hernando, Diego; Bannas, Peter; Holmes, James H; Wang, Kang; Shimakawa, Ann; Iwadate, Yuji; Taviani, Valentina; Rehm, Jennifer L; Reeder, Scott B

2015-11-01

To evaluate free-breathing chemical shift-encoded (CSE) magnetic resonance imaging (MRI) for quantification of hepatic proton density fat-fraction (PDFF). A secondary purpose was to evaluate hepatic R2* values measured using free-breathing quantitative CSE-MRI. Fifty patients (mean age, 56 years) were prospectively recruited and underwent the following four acquisitions to measure PDFF and R2*; 1) conventional breath-hold CSE-MRI (BH-CSE); 2) respiratory-gated CSE-MRI using respiratory bellows (BL-CSE); 3) respiratory-gated CSE-MRI using navigator echoes (NV-CSE); and 4) single voxel MR spectroscopy (MRS) as the reference standard for PDFF. Image quality was evaluated by two radiologists. MRI-PDFF measured from the three CSE-MRI methods were compared with MRS-PDFF using linear regression. The PDFF and R2* values were compared using two one-sided t-test to evaluate statistical equivalence. There was no significant difference in the image quality scores among the three CSE-MRI methods for either PDFF (P = 1.000) or R2* maps (P = 0.359-1.000). Correlation coefficients (95% confidence interval [CI]) for the PDFF comparisons were 0.98 (0.96-0.99) for BH-, 0.99 (0.97-0.99) for BL-, and 0.99 (0.98-0.99) for NV-CSE. The statistical equivalence test revealed that the mean difference in PDFF and R2* between any two of the three CSE-MRI methods was less than ±1 percentage point (pp) and ±5 s(-1) , respectively (P < 0.046). Respiratory-gated CSE-MRI with respiratory bellows or navigator echo are feasible methods to quantify liver PDFF and R2* and are as valid as the standard breath-hold technique. © 2015 Wiley Periodicals, Inc.

Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in Patients With Hepatic Metastases of Neuroendocrine Tumors.

PubMed

Sänger, Philipp Wilhelm; Freesmeyer, Martin

2016-06-01

Whole-body PET with Ga-DOTA-D-Phe-Tyr-octreotide (Ga-DOTATOC) and contrast-enhanced CT (ceCT) are considered a standard for the staging of neuroendocrine tumors (NETs). This study sought to verify whether early dynamic (ed) Ga-DOTATOC PET/CT can reliably detect liver metastases of NETs (hypervascular, nonhypervascular; positive or negative for somatostatin receptors) and to verify if the receptor positivity has a significant impact on the detection of tumor hypervascularization. Twenty-seven patients with NET were studied by ceCT and standard whole-body PET according to established Ga-DOTATOC protocols. In addition, edPET data were obtained by continuous scanning during the first 300 seconds after bolus injections of the radiotracer. Early dynamic PET required an additional low-dose, native CT image of the liver for the purpose of attenuation correction. Time-activity and time-contrast curves were obtained, the latter being calculated by the difference between tumor and reference regions. Early dynamic PET/CT proved comparable with ceCT in readily identifying hypervascular lesions, irrespective of the receptor status, with activities rising within 16 to 40 seconds. Early dynamic PET/CT also readily identified nonhypervascular, receptor-positive lesions. Positive image contrasts were obtained for hypervascular, receptor-positive lesions, whereas early negative contrasts were obtained for nonhypervascular, receptor-negative lesions. The high image contrast of hypervascular NET metastases in early arterial phases suggests that edPET/CT can become a useful alternative in patients with contraindications to ceCT. The high density of somatostatin receptors did not seem to interfere with the detection of the lesion's hypervascularization.

Rational Drug Discovery of HCV Helicase Inhibitor: Improved Docking Accuracy with Multiple Seeding in AutoDock Vina and In Situ Minimization.

PubMed

Lim, See K; Othman, Rozana; Yusof, Rohana; Heh, Choon H

2017-01-01

Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximately 3% of the global populations. Despite the current several direct antiviral agents in the treatment of Hepatitis C, the standard treatment for HCV infection is accompanied by several drawbacks, such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. To discover potential inhibitors for HCV helicase through an optimized in silico approach. In this study, a homology model (HCV Genotype 3 helicase) was used as the target and screened through a benzopyran-based virtual library. Multiple-seedings of AutoDock Vina and in situ minimization were to account for the non-deterministic nature of AutoDock Vina search algorithm and binding site flexibility, respectively. ADME/T and interaction analyses were also done on the top hits via FAFDRUG3 web server and Discovery Studio 4.5. This study involved the development of an improved flow for virtual screening via implemention of multiple-seeding screening approach and in situ minimization. With the new docking protocol, the redocked standards have shown better RMSD value in reference to their native conformations. Ten benzopyran-like compounds with satisfactory physicochemical properties were discovered to be potential inhibitors of HCV helicase. ZINC38649350 was identified as the most potential inhibitor. Ten potential HCV helicase inhibitors were discovered via a new docking optimization protocol with better docking accuracy. These findings could contribute to the discovery of novel HCV antivirals and serve as an alternative approach of in silico rational drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Application of traditional Chinese medicine reference standards in quality control of Chinese herbal pieces].

PubMed

Lu, Tu-Lin; Li, Jin-Ci; Yu, Jiang-Yong; Cai, Bao-Chang; Mao, Chun-Qin; Yin, Fang-Zhou

2014-01-01

Traditional Chinese medicine (TCM) reference standards plays an important role in the quality control of Chinese herbal pieces. This paper overviewed the development of TCM reference standards. By analyzing the 2010 edition of Chinese pharmacopoeia, the application of TCM reference standards in the quality control of Chinese herbal pieces was summarized, and the problems exiting in the system were put forward. In the process of improving the quality control level of Chinese herbal pieces, various kinds of advanced methods and technology should be used to research the characteristic reference standards of Chinese herbal pieces, more and more reasonable reference standards should be introduced in the quality control system of Chinese herbal pieces. This article discussed the solutions in the aspect of TCM reference standards, and future development of quality control on Chinese herbal pieces is prospected.

Controlled Attenuation Parameter and Liver Stiffness Measurements for Steatosis Assessment in the Liver Transplant of Brain Dead Donors.

PubMed

Mancia, Claire; Loustaud-Ratti, Véronique; Carrier, Paul; Naudet, Florian; Bellissant, Eric; Labrousse, François; Pichon, Nicolas

2015-08-01

One of the main selection criteria of the quality of a liver graft is the degree of steatosis, which will determine the success of the transplantation. The aim of this study was to evaluate the ability of FibroScan and its related methods Controlled Attenuation Parameter and Liver Stiffness to assess objectively steatosis and fibrosis in livers from brain-dead donors to be potentially used for transplantation. Over a period of 10 months, 23 consecutive brain dead donors screened for liver procurement underwent a FibroScan and a liver biopsy. The different predictive models of liver retrievability using liver biopsy as the gold standard have led to the following area under receiver operating characteristic curve: 76.6% (95% confidence intervals [95% CIs], 48.2%-100%) when based solely on controlled attenuation parameter, 75.0% (95% CIs, 34.3%-100%) when based solely on liver stiffness, and 96.7% (95% CIs, 88.7%-100%) when based on combined indices. Our study suggests that a preoperative selection of brain-dead donors based on a combination of both Controlled Attenuation Parameter and Liver Stiffness obtained with FibroScan could result in a good preoperative prediction of the histological status and degree of steatosis of a potential liver graft.

Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

PubMed Central

Bessone, Fernando; Poles, Natalia; Roma, Marcelo G

2014-01-01

Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis. PMID:25018850

Experimental verification of stopping-power prediction from single- and dual-energy computed tomography in biological tissues

NASA Astrophysics Data System (ADS)

Möhler, Christian; Russ, Tom; Wohlfahrt, Patrick; Elter, Alina; Runz, Armin; Richter, Christian; Greilich, Steffen

2018-01-01

An experimental setup for consecutive measurement of ion and x-ray absorption in tissue or other materials is introduced. With this setup using a 3D-printed sample container, the reference stopping-power ratio (SPR) of materials can be measured with an uncertainty of below 0.1%. A total of 65 porcine and bovine tissue samples were prepared for measurement, comprising five samples each of 13 tissue types representing about 80% of the total body mass (three different muscle and fatty tissues, liver, kidney, brain, heart, blood, lung and bone). Using a standard stoichiometric calibration for single-energy CT (SECT) as well as a state-of-the-art dual-energy CT (DECT) approach, SPR was predicted for all tissues and then compared to the measured reference. With the SECT approach, the SPRs of all tissues were predicted with a mean error of (-0.84  ±  0.12)% and a mean absolute error of (1.27  ±  0.12)%. In contrast, the DECT-based SPR predictions were overall consistent with the measured reference with a mean error of (-0.02  ±  0.15)% and a mean absolute error of (0.10  ±  0.15)%. Thus, in this study, the potential of DECT to decrease range uncertainty could be confirmed in biological tissue.

Classification Features of US Images Liver Extracted with Co-occurrence Matrix Using the Nearest Neighbor Algorithm

NASA Astrophysics Data System (ADS)

Moldovanu, Simona; Bibicu, Dorin; Moraru, Luminita; Nicolae, Mariana Carmen

2011-12-01

Co-occurrence matrix has been applied successfully for echographic images characterization because it contains information about spatial distribution of grey-scale levels in an image. The paper deals with the analysis of pixels in selected regions of interest of an US image of the liver. The useful information obtained refers to texture features such as entropy, contrast, dissimilarity and correlation extract with co-occurrence matrix. The analyzed US images were grouped in two distinct sets: healthy liver and steatosis (or fatty) liver. These two sets of echographic images of the liver build a database that includes only histological confirmed cases: 10 images of healthy liver and 10 images of steatosis liver. The healthy subjects help to compute four textural indices and as well as control dataset. We chose to study these diseases because the steatosis is the abnormal retention of lipids in cells. The texture features are statistical measures and they can be used to characterize irregularity of tissues. The goal is to extract the information using the Nearest Neighbor classification algorithm. The K-NN algorithm is a powerful tool to classify features textures by means of grouping in a training set using healthy liver, on the one hand, and in a holdout set using the features textures of steatosis liver, on the other hand. The results could be used to quantify the texture information and will allow a clear detection between health and steatosis liver.

Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

2005-01-01

In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. For the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

Hepatoprotective activity of petroleum ether, diethyl ether, and methanol extract of Scoparia dulcis L. against CCl4-induced acute liver injury in mice

PubMed Central

Praveen, T.K.; Dharmaraj, S.; Bajaj, Jitendra; Dhanabal, S.P.; Manimaran, S.; Nanjan, M.J.; Razdan, Rema

2009-01-01

Objectives: The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM) extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. Materials and Methods: The PDM extract (50, 200, and 800 mg/kg, p.o.) and standard, silymarin (100 mg/kg, p.o) were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. Results: The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05) and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.). In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 ± 1.0 μg/ml). Conclusions: The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents. PMID:20442817

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

DOE PAGES

Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; ...

2014-06-10

HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to ε max) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001).more » A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

The isolation of primary hepatocytes from human tissue: optimising the use of small non-encapsulated liver resection surplus.

PubMed

Green, Charlotte J; Charlton, Catriona A; Wang, Lai-Mun; Silva, Michael; Morten, Karl J; Hodson, Leanne

2017-12-01

Two-step perfusion is considered the gold standard method for isolating hepatocytes from human liver tissue. As perfusion may require a large tissue specimen, which is encapsulated and has accessible vessels for cannulation, only a limited number of tissue samples may be suitable. Therefore, the aim of this work was to develop an alternative method to isolate hepatocytes from non-encapsulated and small samples of human liver tissue. Healthy tissue from 44 human liver resections were graded for steatosis and tissue weights between 7.8 and 600 g were used for hepatocyte isolations. Tissue was diced and underwent a two-step digestion (EDTA and collagenase). Red cell lysis buffer was used to prevent red blood cell contamination and toxicity. Isolated hepatocyte viability was determined by trypan blue exclusion. Western blot and biochemical analyses were undertaken to ascertain cellular phenotype and function. Liver tissue that weighed ≥50 g yielded significantly higher (P < 0.01) cell viability than tissue <50 g. Viable cells secreted urea and displayed the phenotypic hepatocyte markers albumin and cytochrome P450. Presence of steatosis in liver tissue or intra-hepatocellular triglyceride content had no effect on cell viability. This methodology allows for the isolation of viable primary human hepatocytes from small amounts of "healthy" resected liver tissue which are not suitable for perfusion. This work provides the opportunity to increase the utilisation of resection surplus tissue, and may ultimately lead to an increased number of in vitro cellular studies being undertaken using the gold-standard model of human primary hepatocytes.

Development of a diaphragmatic motion-based elastography framework for assessment of liver stiffness

NASA Astrophysics Data System (ADS)

Weis, Jared A.; Johnsen, Allison M.; Wile, Geoffrey E.; Yankeelov, Thomas E.; Abramson, Richard G.; Miga, Michael I.

2015-03-01

Evaluation of mechanical stiffness imaging biomarkers, through magnetic resonance elastography (MRE), has shown considerable promise for non-invasive assessment of liver stiffness to monitor hepatic fibrosis. MRE typically requires specialized externally-applied vibratory excitation and scanner-specific motion-sensitive pulse sequences. In this work, we have developed an elasticity imaging approach that utilizes natural diaphragmatic respiratory motion to induce deformation and eliminates the need for external deformation excitation hardware and specialized pulse sequences. Our approach uses clinically-available standard of care volumetric imaging acquisitions, combined with offline model-based post-processing to generate volumetric estimates of stiffness within the liver and surrounding tissue structures. We have previously developed a novel methodology for non-invasive elasticity imaging which utilizes a model-based elasticity reconstruction algorithm and MR image volumes acquired under different states of deformation. In prior work, deformation was external applied through inflation of an air bladder placed within the MR radiofrequency coil. In this work, we extend the methodology with the goal of determining the feasibility of assessing liver mechanical stiffness using diaphragmatic respiratory motion between end-inspiration and end-expiration breath-holds as a source of deformation. We present initial investigations towards applying this methodology to assess liver stiffness in healthy volunteers and cirrhotic patients. Our preliminary results suggest that this method is capable of non-invasive image-based assessment of liver stiffness using natural diaphragmatic respiratory motion and provides considerable enthusiasm for extension of our approach towards monitoring liver stiffness in cirrhotic patients with limited impact to standard-of-care clinical imaging acquisition workflow.

Heavy Metal Accumulation is Associated with Molecular and Pathological Perturbations in Liver of Variola louti from the Jeddah Coast of Red Sea.

PubMed

Mohamed, Saleh A; Elshal, Mohamed F; Kumosani, Taha A; Mal, Ahmad O; Ahmed, Youssri M; Almulaiky, Yaaser Q; Asseri, Amer H; Zamzami, Mazin A

2016-03-21

Large amounts of waste water are discharged daily from the Jeddah Metropolitan Area into the Red Sea. Sewage draining into the Red Sea causes widespread chemical pollution that is toxic to aquatic ecosystems. The objective of this study was to investigate the extent of pollution and assess the presence of heavy metals in fish tissue and study their association with biological and biochemical alterations. The average concentrations of heavy metals found in hepatic tissues of Variola louti fish from the polluted area, namely Cd, Cr, Cu, Fe and Zn, were 1.74, 9.69, 47.48, 4020.01 and 229.47 µg/g liver, respectively, that were significantly higher than that of samples taken from reference area (0.24, 1.98, 20.12, 721.93, 129.21 µg/g liver, respectively). The fold change of heavy metals in fish from the polluted area with respect of that of the reference area followed the order Cd > Fe > Cr > Cu > Zn. Analysis of nuclear DNA revealed that hepatic tissues of fish samples from the polluted area showed a significant increase in apoptotic cells as detected by flow cytometry and formation DNA-ladder. In addition, hepatic sections from polluted area fishes showed more fibrotic changes and collagen deposition by hematoxylin-eosin staining and Masson's trichrome staining, respectively, compared to samples taken from the reference area. Moreover, the electrophoretic patterns of proteins of liver of fishes caught at the polluted area showed different patterns of proteins from that of the reference with bands at 42, 130 and 140 kDa, which is in a good agreement with the molecular weight of collagen type III. In conclusion, there were significant changes in the tissues of fishes in the polluted area at the cellular and the molecular levels that may be associated with an accumulation of heavy metals. Assessment of fishes as a sensitive biomonitor for the pollution of surface waters that may affect general health of human and wild life is conceivable.

Assessment of metals exposure and sub-lethal effects in voles and small birds captured near the DeLong Mountain Regional Transportation System Road, Cape Krusenstern National Monument, Alaska, 2006

USGS Publications Warehouse

Brumbaugh, William G.; Mora, Miguel A.; May, Thomas W.

2008-01-01

Voles (n=6) and small ground-nesting birds (n=12) were live-captured near the DeLong Mountain Regional Transportation System haul road in Cape Krusenstern National Monument in northwest Alaska in 2006 to assess metals exposure and sub-lethal biological effects. Similar numbers of animals were captured from a reference site in southern Cape Krusenstern National Monument for comparison. Histopathological examination of selected organs, blood analysis, and analysis for aluminum, barium, cadmium, lead, and zinc concentrations in liver and blood samples were performed. Voles and small birds captured from near the haul road had about 20 times greater blood and liver lead concentrations and about 3 times greater cadmium concentrations when compared to those from the reference site. Barium and zinc tissue concentrations of animals collected from different sites were not remarkably different, and aluminum concentrations were below the reporting limits in most samples. There was no clear evidence of serious sub-lethal biological effects such as lesions in internal organs or DNA damage in blood in any of the animals. Accordingly, blood and liver lead concentrations in animals captured near the haul road generally were less than tissue concentration thresholds associated with serious biological effects reported from other studies; however, subtle effects resulting from lead exposure, such as the suppression of the activity of certain enzymes, cannot be ruled out for those animals nearest the haul road. Notably, liver lead concentrations of voles and small birds at the reference location were considerably less than those previously reported for similar animals at reference sites in other parts of the United States, Canada, and Europe. Results from this reconnaissance-level study indicate that voles and small birds inhabiting this area are not suffering serious biological effects as a result of metals exposure; however, continued monitoring of lead and other metals is recommended because of uncertainties noted and because biological effects thresholds might be approached if exposure levels were to increase.

Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research

PubMed Central

Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

2018-01-01

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a “digital biopsy” for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver. PMID:29527259

Hot topics in liver transplantation: organ allocation--extended criteria donor--living donor liver transplantation.

PubMed

Müllhaupt, Beat; Dimitroulis, Dimitrios; Gerlach, J Tilman; Clavien, Pierre-Alain

2008-01-01

Liver transplantation has become the mainstay for the treatment of end-stage liver disease, hepatocellular cancer and some metabolic disorders. Its main drawback, though, is the disparity between the number of donors and the patients needing a liver graft. In this review we will discuss the recent changes regarding organ allocation, extended donor criteria, living donor liver transplantation and potential room for improvement. The gap between the number of donors and patients needing a liver graft forced the transplant community to introduce an objective model such as the modified model for end-stage liver disease (MELD) in order to obtain a transparent and fair organ allocation system. The use of extended criteria donor livers such as organs from older donors or steatotic grafts is one possibility to reduce the gap between patients on the waiting list and available donors. Finally, living donor liver transplantation has become a standard procedure in specialized centers as another possibility to reduce the donor shortage. Recent data clearly indicate that center experience is of major importance in achieving good results. Great progress has been made in recent years. However, further research is needed to improve results in the future.

Laparoscopic Splenectomy with Technical Standardization and Selection Criteria for Standard or Hand-Assisted Approach in 390 Patients with Liver Cirrhosis and Portal Hypertension.

PubMed

Kawanaka, Hirofumi; Akahoshi, Tomohiko; Kinjo, Nao; Harimoto, Norifumi; Itoh, Shinji; Tsutsumi, Norifumi; Matsumoto, Yoshihiro; Yoshizumi, Tomoharu; Shirabe, Ken; Maehara, Yoshihiko

2015-08-01

Laparoscopic splenectomy (LS) is still challenging in patients with liver cirrhosis and portal hypertension. This study was designed to establish safe and less invasive LS in patients with liver cirrhosis and portal hypertension. We analyzed 390 patients with liver cirrhosis and portal hypertension, who underwent LS between 1993 and 2013. Patients were divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008, n = 159); and late (2008 to 2013, n = 125). During the middle time period, standardized technique for LS and selection criteria for hand-assisted LS were adopted. Patients with spleen volume ≥ 1,000 mL by CT volumetry, large perisplenic collateral vessels, and/or Child-Pugh score ≥ 9, underwent hand-assisted LS. During the late time period, the selection criteria were refined and patients with spleen volume ≥ 600 mL underwent hand-assisted LS. Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in the middle time period, and 3.2% in the late time period, p = 0.004), median blood loss decreased (300g, 87g, and 98g, respectively, p < 0.001), and the success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively, p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p = 0.081), and technique-related complications decreased significantly (10.4%, 3.8%, and 2.4%, respectively, p = 0.014). Laparoscopic splenectomy is now a safe and less invasive approach, even in patients with liver cirrhosis and portal hypertension, because of its technical standardization with the refined selection criteria for pure or hand-assisted LS. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

CT liver volumetry using geodesic active contour segmentation with a level-set algorithm

NASA Astrophysics Data System (ADS)

Suzuki, Kenji; Epstein, Mark L.; Kohlbrenner, Ryan; Obajuluwa, Ademola; Xu, Jianwu; Hori, Masatoshi; Baron, Richard

2010-03-01

Automatic liver segmentation on CT images is challenging because the liver often abuts other organs of a similar density. Our purpose was to develop an accurate automated liver segmentation scheme for measuring liver volumes. We developed an automated volumetry scheme for the liver in CT based on a 5 step schema. First, an anisotropic smoothing filter was applied to portal-venous phase CT images to remove noise while preserving the liver structure, followed by an edge enhancer to enhance the liver boundary. By using the boundary-enhanced image as a speed function, a fastmarching algorithm generated an initial surface that roughly estimated the liver shape. A geodesic-active-contour segmentation algorithm coupled with level-set contour-evolution refined the initial surface so as to more precisely fit the liver boundary. The liver volume was calculated based on the refined liver surface. Hepatic CT scans of eighteen prospective liver donors were obtained under a liver transplant protocol with a multi-detector CT system. Automated liver volumes obtained were compared with those manually traced by a radiologist, used as "gold standard." The mean liver volume obtained with our scheme was 1,520 cc, whereas the mean manual volume was 1,486 cc, with the mean absolute difference of 104 cc (7.0%). CT liver volumetrics based on an automated scheme agreed excellently with "goldstandard" manual volumetrics (intra-class correlation coefficient was 0.95) with no statistically significant difference (p(F<=f)=0.32), and required substantially less completion time. Our automated scheme provides an efficient and accurate way of measuring liver volumes.

Resection of Large Metachronous Liver Metastasis with Gastric Origin: Case Report and Review of the Literature

PubMed Central

Runcanu, Alexandru; Paun, Sorin; Negoi, Ruxandra Irina; Beuran, Mircea

2016-01-01

Introduction: Increasing evidence suggests that surgical resection may be offered to a subgroup of patients with liver metastasis of gastric adenocarcinoma. The aim of this case report is to illustrate the surgical resection of a single liver metachronous recurrence twelve months after a radical total gastrectomy for cancer. Case report: A 63-year-old male patient with an Eastern Cooperative Oncology Group performance status of 1 was referred to our hospital for a single, large liver metastasis, twelve months after a radical total gastrectomy and DII lymphadenectomy for upper third gastric adenocarcinoma. As the adjuvant treatment, the patient received 12 cycles of FOLFOX chemotherapy. During the present admission, the abdominal computed tomography (CT) revealed a single liver metastasis located in the segments 5 and 6, of 105/85 mm in diameter. Surgical resection by an open approach of liver metastasis was decided. We performed a non-anatomical liver resection, without inflow control due to significant peritoneal adhesions in the liver hilum secondary to the previous lymphadenectomy. The patient was discharged after seven days, with an uneventful recovery. Six months after the second surgical procedure, the patient developed a local liver recurrence. The surgical resection of the liver recurrence was performed, with no postoperative morbidities, and the patient was discharged after eight days. Three months after the latest surgery, the patient is under adjuvant chemotherapy, with no imagistic signs of further recurrences. Conclusions:  Hepatic resection for liver metastasis of gastric origin may offer satisfactory oncological outcomes in a very selected subgroup of patients. PMID:27843732

Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.

PubMed

Woodhouse, C A; Patel, V C; Singanayagam, A; Shawcross, D L

2018-01-01

Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis. © 2017 John Wiley & Sons Ltd.

Synthesis of Alkyl-Glycerolipids Standards for Gas Chromatography Analysis: Application for Chimera and Shark Liver Oils

PubMed Central

Pinault, Michelle; Guimaraes, Cyrille; Couthon, Hélène; Thibonnet, Jérôme; Fontaine, Delphine; Chantôme, Aurélie; Chevalier, Stephan; Jaffrès, Paul-Alain; Vandier, Christophe

2018-01-01

Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20–24%), 16:0 (42–54%) and 18:1 (6–16%) and, to a lesser extent, (0.2–2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues. PMID:29570630

Vitamin A toxicity in wild-caught African green vervet monkeys (Chlorocebus aethiops) after 2 years in captivity.

PubMed

Mills, Jordan P; Tanumihardjo, Sherry A

2006-10-01

Primate lab diets typically contain high vitamin A concentrations when compared with human recommended intakes. In this study, we analyzed the vitamin A contents of liver and serum from 13 adult female African green vervet monkeys (Chlorocebus aethiops). These monkeys were wild-caught and held in captivity for 2 y, during which time they consumed a standard primate diet. Liver vitamin A concentration (mean +/- 1 standard deviation) was 14.6 +/- 2.3 micromol retinol/g liver; subtoxicity in humans is defined as at least 1 micromol/g liver. The serum retinol concentration (0.93 +/- 0.21 microM) was not elevated. Hypertrophy and hyperplasia of hepatic stellate cells were present which, in conjunction with elevated hepatic vitamin A concentrations, are evidence of toxicity. Although the ramifications of chronically toxic vitamin A status in experimental monkeys have not been defined, this state may influence nonhuman primate research outcomes and confound data interpretation. The validity of bone mineral research using nonhuman primates is of greatest concern, in light of the association between vitamin A toxicity and compromised bone health.

Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient.

PubMed

Hardie, Andrew D; Egbert, Robert E; Rissing, Michael S

2015-01-01

Diffusion-weighted magnetic resonance imaging (DW-MR) can be useful in the differentiation of hemangiomata from liver metastasis, but improved methods other than by mean apparent diffusion coefficient (mADC) are needed. A retrospective review identified 109 metastatic liver lesions and 86 hemangiomata in 128 patients who had undergone DW-MR. For each lesion, mADC and the standard deviation of the mean ADC (sdADC) were recorded and compared by receiver operating characteristic analysis. Mean mADC was higher in benign hemangiomata (1.52±0.12 mm(2)/s) than in liver metastases (1.33±0.18 mm(2)/s), but there was significant overlap in values. The mean sdADC was lower in hemangiomata (101±17 mm(2)/s) than metastases (245±25 mm(2)/s) and demonstrated no overlap in values, which was significantly different (P<.0001). Hemangiomata may be better able to be differentiated from liver metastases on the basis of sdADC than by mADC, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective effects of the herbal medicine goshajinkigan in a rat model of non-alcoholic fatty liver disease.

PubMed

Hirotani, Yoshihiko; Doi, Ayae; Takahashi, Tomoki; Umezawa, Hanako; Urashima, Yoko; Myotoku, Mitiaki

2012-12-01

This study was designed to investigate the effect of an herbal medicine-goshajinkigan (GJ)-on the regulation of total body weight, as well as liver and adipose tissue weights in rats fed a highfat diet (HFD) and drinking of 30% sucrose (HFDS) (HFD; the rats received 19.6% energy from carbohydrates, 18.2% from proteins, and 62.2% from lipids; total energy, 506 kcal/100 g). Control rats were fed a standard diet (the rats received 60.5% energy from carbohydrates, 26.2% from proteins, and 13.3% from lipids; total energy, 360 kcal/100 g). Over a period of 12 weeks, rats were allowed free access to either the standard diet or HFDS containing 0, 1, or 3% GJ. In comparison with the control group, the HFDS rats showed a significant decrease in overall body weight and adipose tissue weight, and an increase in liver weight at 12 weeks. GJ treatment significantly reversed the HFDS-induced decrease in body and adipose tissue weight and reduced the elevated liver weight dose-dependently. Similarly, GJ reduced the elevated serum aspartate aminotransferase levels observed in HFDS rats. These results suggest that GJ may have the potential to alleviate damage to the liver in subjects with long-term consumption of HFDS.

Genetics Home Reference: arginase deficiency

MedlinePlus

... occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, ... the urea cycle, which produces urea by removing nitrogen from arginine. In people with arginase deficiency , arginase ...

Genetics Home Reference: nephronophthisis

MedlinePlus

... which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

Infrahepatic vena cavocavostomy, a modification of the piggyback technique for liver transplantation.

PubMed

Khanmoradi, Kamran; Defaria, Werviston; Nishida, Seigo; Levi, David; Kato, Tomoaki; Moon, Jang; Selvaggi, Gennaro; Tzakis, Andreas

2009-05-01

We describe our experience with a modification of the piggyback (PB) technique for orthotopic liver transplantation in which the donor infrahepatic vena cava is used as the venous outflow tract. From May 1997 to January 2006, a total of 109 cases using this technique were performed in 101 patients. Collected data included recipient demographics and diagnosis, warm ischemia time, use of venovenous bypass or temporary portacaval shunt and complications related to the venous outflow and graft, and patient survival. Data were compared with the patients undergoing standard PB technique during the same period. The reasons for using the technique were grouped according to whether there was a problem with the recipient hepatic veins or a concern about the length or diameter of the donor suprahepatic vena cava. These included the presence of a transjugular intrahepatic portosystemic shunt (eight cases), retransplantation (22 cases), thin-walled, friable hepatic veins (32 cases), Budd-Chiari syndrome (two cases), domino liver procurement (six cases), reduced or split liver grafts (five cases), and graft inferior vena cava to recipient hepatic veins size discrepancy (34 cases). There was no graft loss. The warm ischemia time was 39.65 minutes compared with 37 minutes in the standard PB group. The long-term graft and patient survival rates were similar in the two groups. Infrahepatic vena cavocavostomy is a useful variation of the standard PB technique.

In vivo organ mass of Korean adults obtained from whole-body magnetic resonance data.

PubMed

Park, S; Lee, J K; Kim, J I; Lee, Y J; Lim, Y K; Kim, C S; Lee, C

2006-01-01

In vivo organ mass of the Korean adult, male and female were presented for the purpose of radiation protection. A total of 121 healthy volunteers (66 males and 55 females), whose body dimensions were close to that of average Korean adults, were recruited for this study. Whole-body magnetic resonance (MR) images were obtained, and contours of 15 organs (brain, eye, gall bladder, heart, kidney, liver, lung, pancreas, stomach, spleen, testes, thymus, thyroid, urinary bladder and uterus) and 9 bones (femur, tibia + fibula, humerus, radius + ulna, pelvis, cervical spine, thoracic and lumber spine, skull and clavicle) were segmented for organ volume rendering by anatomists using commercial software. Organ and bone masses were calculated by multiplying the Asian reference densities of the corresponding organs and bones by the measured volumes. The resulting organ and bone masses were compared with those of the International Commission of Radiological Protection (ICRP) and the Asian reference data. Significantly large standard deviation was shown in the moving organs of the respiratory and circulatory systems and in the alimentary and urogenital organs that are variable in volume in a single person. Gall bladder and pancreas showed unique Korean organ masses compared with those of ICRP and the Asian reference adults. Different from anatomical data based on autopsy, the in vivo volume and mass in this study can more exactly describe the organ volume of a living human subject for radiation protection. A larger sample size would be required for obtaining statistically more reliable results. It is also needed to establish the reference organ mass of younger age groups for which it is difficult to recruit volunteers and to immobilise the subjects for long-time MR scanning. At present, the data from this study will contribute to the establishment of a Korean reference database.

Hepatic steatosis and fibrosis: Non-invasive assessment

PubMed Central

Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D

2016-01-01

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096

Advances in the use of milk thistle (Silybum marianum).

PubMed

Post-White, Janice; Ladas, Elena J; Kelly, Kara M

2007-06-01

Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.

The significance of 99mTc-MAA SPECT/CT liver perfusion imaging in treatment planning for 90Y-microsphere selective internal radiation treatment.

PubMed

Ahmadzadehfar, Hojjat; Sabet, Amir; Biermann, Kim; Muckle, Marianne; Brockmann, Holger; Kuhl, Christiane; Wilhelm, Kai; Biersack, Hans-Jürgen; Ezziddin, Samer

2010-08-01

Selective internal radiation therapy (SIRT), a catheter-based liver-directed modality for treating primary and metastatic liver cancer, requires appropriate planning to maximize its therapeutic response and minimize its side effects. (99m)Tc-macroaggregated albumin (MAA) scanning should precede the therapy to detect any extrahepatic shunting to the lung or gastrointestinal tract. Our aim was to compare the ability of SPECT/CT with that of planar imaging and SPECT in the detection and localization of extrahepatic (99m)Tc-MAA accumulation and to evaluate the impact of SPECT/CT on SIRT treatment planning and its added value to angiography in this setting. Ninety diagnostic hepatic angiograms with (99m)Tc-MAA were obtained for 76 patients with different types of cancer. All images were reviewed retrospectively for extrahepatic MAA deposition in the following order: planar, non-attenuation-corrected SPECT, and SPECT/CT. Review of angiograms and follow-up of patients with abdominal shunting served as reference standards. Extrahepatic accumulation was detected by planar imaging, SPECT, and SPECT/CT in 12%, 17%, and 42% of examinations, respectively. The sensitivity for detecting extrahepatic shunting with planar imaging, SPECT, and SPECT/CT was 32%, 41%, and 100%, respectively; specificity was 98%, 98%, and 93%, respectively. The respective positive predictive values were 92%, 93%, and 89%, and the respective negative predictive values were 71%, 73%, and 100%. The therapy plan was changed according to the results of planar imaging, SPECT, and SPECT/CT in 7.8%, 8.9%, and 29% of patients, respectively. In pre-SIRT planning, (99m)Tc-MAA SPECT/CT is valuable for identifying extrahepatic visceral sites at risk for postradioembolization complications.

Feasibility of balanced steady-state free precession sequence at 1.5T for the evaluation of hepatic steatosis in obese children and adolescents.

PubMed

Zhang, Hong-Xi; Fu, Jun-Fen; Lai, Can; Tian, Feng-Yu; Su, Xiao-Li; Huang, Ke

2018-04-30

To determine the feasibility of balanced steady-state free precession (b-SSFP) imaging for measuring hepatic steatosis in obese children and adolescents, using proton magnetic resonance spectroscopy ( 1 H MRS) as reference standard. 182 obese Chinese paediatric patients underwent conventional T1-weighted dual echo MRI, 1 H MRS and b-SSFP imaging for non-invasive assessment of hepatic steatosis. There was a strong positive correlation between liver fat fraction (FF) on T1-weighted dual echo MRI and 1 H MRS-determined liver fat content (LFC) (r = 0.964, p < .001), and a strong negative correlation between the ratio of liver signal intensity (SI) to spleen SI (L/S) on b-SSFP and LFC (r = -0.896, p < .001). ROC curve analysis based on a diagnostic threshold of 1 H MRS-determined LFC >50 mg/g (>5 % by wet weight) showed areas under the curves for FF and L/S at 0.989 (0.976-1.000) and 0.926 (0.888-0.964), respectively. Optimal FF and L/S cut-off values identified patients with hepatic steatosis with 97.9 % and 86.5 % sensitivity and 93.4 % and 93.4 % specificity, respectively. Following further validation, b-SSFP at 1.5T has potential as a feasible technique for evaluation of hepatic steatosis in obese paediatric patients with limited breath-holding capacity. • L/S on b-SSFP images closely correlated with 1 H MRS-determined LFC. • b-SSFP has high diagnostic accuracy for hepatic steatosis in obese children. • 100% of obese paediatric subjects are imaged successfully using b-SSFP sequence. • b-SSFP has potential to evaluate hepatic steatosis in children with poor breath-hold.

Liver pathology of hepatitis C, beyond grading and staging of the disease

PubMed Central

Dhingra, Sadhna; Ward, Stephen C; Thung, Swan N

2016-01-01

Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other non-viral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection. PMID:26819505

Liver phospholipids fatty acids composition in response to different types of diets in rats of both sexes.

PubMed

Ranković, Slavica; Popović, Tamara; Martačić, Jasmina Debeljak; Petrović, Snježana; Tomić, Mirko; Ignjatović, Đurđica; Tovilović-Kovačević, Gordana; Glibetić, Maria

2017-05-19

Dietary intake influence changes in fatty acids (FA) profiles in liver which plays a central role in fatty acid metabolism, triacylglycerol synthesis and energy homeostasis. We investigated the effects of 4-weeks treatment with milk- and fish-based diet, on plasma biochemical parameters and FA composition of liver phospholipids (PL) in rats of both sexes. Adult, 4 months old, Wistar rats of both sexes, were fed with different types of diets: standard, milk-based and fish-based, during 4 weeks. Analytical characterization of different foods was done. Biochemical parameters in plasma were determined. Fatty acid composition was analyzed by gas-chromatography. Statistical significance of FA levels was tested with two-way analysis of variance (ANOVA) using the sex of animals and treatment (type of diet) as factors on logarithmic or trigonometric transformed data. Our results showed that both, milk- and fish-based diet, changed the composition and ratio of rat liver phospholipids FA, in gender-specific manner. Initially present sex differences appear to be dietary modulated. Although, applied diets changed the ratio of total saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), and effects were gender specific. Milk-based diet lowered SFA and elevated MUFA in males and increased PUFA in females vs. standard diet. The same diet decreased n-3, increased n-6 and n-6/n-3 ratio in males. Fish-based diet increased n-3, decreased n-6 and n-6/n-3 ratio vs. standard and milk-based diet in females. However, the ratio of individual FA in liver PL was also dietary-influenced, but with gender specific manner. While in females fish-based diet decreased AA (arachidonic acid) increased level of EPA (eicosapentaenoic acid), DPA (docosapentaenoic acid) and DHA (docosahexaenoic acid), the same diet elevated only DHA levels in males. Gender related variations in FA composition of rat liver PL were observed, and results have shown that those initial differences could be significantly modulated by the type of diet. Furthermore, the modulatory effects of milk- and fish-based diets on liver phospholipids FA profiles appeared to be sex-specific.

[The determination of the natural content of chemical elements in human biological objects (liver, kidney, stomach) by mass spectrometry with inductively coupled plasma].

PubMed

Luzanova, I S; Svetlolobov, D Iu; Zorin, Iu V

2014-01-01

The objective of the present work was to continue the studies of the sites of concentration of the chemical elements corresponding to normal homeostasis in human biological objects by mass spectrometry with inductively coupled plasma. The study yielded the data on the natural content of 27 elements in the cadaveric liver, kidney, and stomach. It is recommended to use these findings as the reference parameters corresponding to normal homeostasis.

Dichlorvos Exposure Results in Large Scale Disruption of Energy Metabolism in the Liver of the Zebra Fish, Danio Rerio

DTIC Science & Technology

2015-10-24

zebrafish reference genome sequence and its relationship to the human genome . Nature. 2013;496(7446):498–503. 21. Linney E, Upchurch L, Donerly S. Zebrafish...To obtain a broader understanding of the effects of dichlorvos on liver metabolism, we per- formed a genome -wide analysis of gene expression in the ...condition) for whole genome transcript ana- lysis, and fixed another set of fish for histological evaluation (n = 5/condition). We determined the target

Fourteen-Day Subacute Intravenous Toxicity Study of Hypertonic Saline/ Dextran 70 and its Constituents in Beagle Dogs

DTIC Science & Technology

1989-11-01

hepatic changes. The magnitude of the enzyme elevations, subsequent decreases in ALK and ALT levels, and -e absence of morphologic changes in the liver...of PT and A-PTT are not uncommon findings in severe, acute, hepatopathies in dogs (17). The increases in hepatic enzymes observed in HSD- and D70...clinical signs referable to liver disease, and the lack of .eaato lesions on histopathological examination, suggest tat the enzyme elevations may have

Liver elastography, comments on EFSUMB elastography guidelines 2013

PubMed Central

Cui, Xin-Wu; Friedrich-Rust, Mireen; Molo, Chiara De; Ignee, Andre; Schreiber-Dietrich, Dagmar; Dietrich, Christoph F

2013-01-01

Recently the European Federation of Societies for Ultrasound in Medicine and Biology Guidelines and Recommendations have been published assessing the clinical use of ultrasound elastography. The document is intended to form a reference and to guide clinical users in a practical way. They give practical advice for the use and interpretation. Liver disease forms the largest section, reflecting published experience to date including evidence from meta-analyses with shear wave and strain elastography. In this review comments and illustrations on the guidelines are given. PMID:24151351

Liver Rapid Reference Set Application: Gary Norman-INOVA (2012) — EDRN Public Portal

Cancer.gov

We have developed a new and novel assay for the detection of Golgi protein 73 (GP73), also known as Golgi membrane protein 1 (Golm1) or Golgi phosphoprotein 2 (Golph2), in serum/plasma. The clinical question is to determine the clinical utility of gp73 antigen detection by the new assay for early hepatocullular carcinoma (HCC) diagnosis, for risk-assessment of patients at high risk for progression of their liver disease, and for prognosis.

Assessment of liver size by ultrasonography.

PubMed

Patzak, Monika; Porzner, Marc; Oeztuerk, Suemeyra; Mason, Richard Andrew; Wilhelm, Manfred; Graeter, Tilmann; Kratzer, Wolfgang; Haenle, Mark Martin; Akinli, Atilla Serif

2014-09-01

To determine liver span sonographically in a randomly selected population sample and identify factors that affect liver size. A total of 1,789 subjects (963 females, 826 males; mean age 41.8 ± 12.8 years) underwent sonographic examination of the liver in the midclavicular line to determine liver span. Subjects underwent physical examination and blood tests and completed a standardized interview questionnaire. The average liver span in the midclavicular line for the overall collective was 15.0 ± 1.5 cm; the average for females was 14.9 ± 1.6 cm and 15.1 ± 1.5 cm for males. Liver span exceeded 16 cm in 24.3% of subjects. Results of the multivariate analysis showed that, of the factors potentially influencing liver span, gender, age, body mass index, body height, fatty liver (p < 0.0001), waist-to-hip ratio (p = 0.015), and metabolic syndrome (p = 0.032) are significant. By contrast, diabetes mellitus, alcohol consumption, tobacco consumption, physical activity, and laboratory findings showed no influence. Sonographic measurement of liver span in the midclavicular line is a simple method for routine clinical use. Gender, age, body mass index, waist-to-hip ratio, body height, hepatic steatosis, and metabolic syndrome are factors associated with liver span. © 2014 Wiley Periodicals, Inc.

Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice.

PubMed

Sebastiani, Giada; Pantopoulos, Kostas

2011-10-01

In healthy subjects, the rate of dietary iron absorption, as well as the amount and distribution of body iron are tightly controlled by hepcidin, the iron regulatory hormone. Disruption of systemic iron homeostasis leads to pathological conditions, ranging from anemias caused by iron deficiency or defective iron traffic, to iron overload (hemochromatosis). Other iron-related disorders are caused by misregulation of cellular iron metabolism, which results in local accumulation of the metal in mitochondria. Brain iron overload is observed in neurodegenerative disorders. Secondary hemochromatosis develops as a complication of another disease. For example, repeated blood transfusions, a standard treatment of various anemias characterized by ineffective erythropoiesis, promote transfusional siderosis, while chronic liver diseases are often associated with mild to moderate secondary iron overload. In this critical review, we discuss pathophysiological and clinical aspects of all types of iron metabolism disorders (265 references). This journal is © The Royal Society of Chemistry 2011

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canini, Laetitia; DebRoy, Swati; Mariño, Zoe

HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to ε max) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001).more » A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications.

PubMed

Grix, Tobias; Ruppelt, Alicia; Thomas, Alexander; Amler, Anna-Klara; Noichl, Benjamin P; Lauster, Roland; Kloke, Lutz

2018-03-22

Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering. Unfortunately, spheroids are limited in size due to diffusion barriers in their dense structures, limiting nutrient and oxygen supply. Recent developments in bioprinting techniques have enabled us to engineer complex 3D structures with perfusion-enabled channel systems to ensure nutritional supply within larger, densely-populated tissue models. In this study, we present a proof-of-concept for the feasibility of bioprinting a liver organoid by combining HepaRG and human stellate cells in a stereolithographic printing approach, and show basic characterization under static cultivation conditions. Using standard tissue engineering analytics, such as immunohistology and qPCR, we found higher albumin and cytochrome P 450 3A4 (CYP3A4) expression in bioprinted liver tissues compared to monolayer controls over a two-week cultivation period. In addition, the expression of tight junctions, liver-specific bile transporter multidrug resistance-associated protein 2 (MRP2), and overall metabolism (glucose, lactate, lactate dehydrogenase (LDH)) were found to be stable. Furthermore, we provide evidence for the perfusability of the organoids' intrinsic channel system. These results motivate new approaches and further development in liver tissue engineering for advanced organ-on-a-chip applications and pharmaceutical developments.

Genetics Home Reference: pyruvate carboxylase deficiency

MedlinePlus

... infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They ... carboxylase allows compounds such as lactic acid and ammonia to build up and damage organs and tissues. ...

Genetics Home Reference: congenital hepatic fibrosis

MedlinePlus

... Home Health Conditions Congenital hepatic fibrosis Congenital hepatic fibrosis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Congenital hepatic fibrosis is a disease of the liver that is ...

Stools - floating

MedlinePlus

... diagnosis. Alternative Names Floating stools Images Lower digestive anatomy References Schiller LR, Sellin JH. Diarrhea. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016: ...

Genetics Home Reference: carbamoyl phosphate synthetase I deficiency

MedlinePlus

... synthetase I. This enzyme participates in the urea cycle, which is a sequence of biochemical reactions that occurs in liver cells. The urea cycle processes excess nitrogen, generated when protein is broken ...

Genetics Home Reference: primary sclerosing cholangitis

MedlinePlus

... with primary sclerosing cholangitis (PSC) in a southern European population. Dig Liver Dis. 2003 Aug;35(8): ... haplotypes in primary sclerosing cholangitis patients from five European populations. Tissue Antigens. 1999 May;53(5):459- ...

Genetics Home Reference: tyrosinemia

MedlinePlus

... in the multistep process that breaks down the amino acid tyrosine, a building block of most proteins. If ... Resources MedlinePlus (4 links) Encyclopedia: Aminoaciduria Health Topic: Amino Acid Metabolism Disorders Health Topic: Liver Diseases Health Topic: ...

Prevalence and outcome of non-alcoholic fatty liver disease in adolescents and young adults undergoing weight loss surgery.

PubMed

Corey, K E; Stanley, T L; Misdraji, J; Scirica, C; Pratt, J; Hoppin, A; Misra, M

2014-10-01

We evaluated the prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in 27 adolescents referred for weight loss surgery (WLS). On biopsy, 18 patients (66.7%) had NAFLD, and of those, 10 (37.0%) had NASH and 11 (40.7%) had fibrosis. Insulin, HbA1C and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in patients with NASH than those without NASH. Following WLS, 40% of patients with NASH had persistently elevated aminotransferase levels despite weight loss. We found that NASH is underdiagnosed in adolescents referred for WLS, and that hyperinsulinaemia, HOMA-IR and HbA1c can aid in identifying high-risk patients. © 2014 The Authors. Pediatric Obesity © 2014 International Association for the Study of Obesity.

Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

PubMed Central

Li, Jian-yuan; Cao, Hong-yan; Cheng, Gen-hong; Sun, Ming-yu

2014-01-01

Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions. PMID:24963489

Status of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return" in advanced liver cirrhosis.

PubMed

Terai, Shuji; Tsuchiya, Atsunori

2017-02-01

The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.

Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors.

PubMed

Mariabeatrice, Principi; Andrea, Iannone; Giuseppe, Losurdo; Michela, Mangia; Endrit, Shahini; Francesca, Albano; Rizzi, Salvatore Fabio; La Fortezza, Rosa Federica; Rosa, Lovero; Antonella, Contaldo; Michele, Barone; Gioacchino, Leandro; Enzo, Ierardi; Alfredo, Di Leo

2018-04-23

Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

Urine stability studies for novel biomarkers of acute kidney injury.

PubMed

Parikh, Chirag R; Butrymowicz, Isabel; Yu, Angela; Chinchilli, Vernon M; Park, Meyeon; Hsu, Chi-Yuan; Reeves, W Brian; Devarajan, Prasad; Kimmel, Paul L; Siew, Edward D; Liu, Kathleen D

2014-04-01

The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers. Cross-sectional prospective. Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36). We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C. Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C. We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs). Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96). No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors. All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25°C before long-term storage or analysis. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voroney, Jon-Paul; Brock, Kristy K.; Eccles, Cynthia

Purpose: The aim of this study was to compare magnetic resonance imaging (MRI) with computed tomography (CT) for liver cancer tumor definition for high-precision radiotherapy planning. Methods and Materials: Diagnostic quality MRI scans and triphasic CT scans, with the liver immobilized in exhale, were obtained at the time of radiation planning for 26 patients with unresectable liver metastases (n = 8), hepatocellular carcinoma (n = 10), and cholangiocarcinoma (n = 8). On the CT and MRI series best demonstrating the tumor, the liver and gross tumor volumes (GTVs) were contoured, and intrahepatic anatomic reference points were identified. Deformable registration wasmore » used to register the liver from the CT with that from the MRI. Results: A difference in the number of tumor foci was seen on CT vs. MRI in 5 patients with hepatocellular carcinoma: MRI showed more foci in 3 patients, CT in 2. After deformable registration of the livers, the population median of the average distance between the CT tumor surface and MRI tumor surface was 3.7 mm (2.2-21.3 mm). The median percentage of tumor surface area that differed by {>=}5 mm was 26% (1-86%). Median percentage concordance volumes were 81% (77-86%) in metastases, 77% (60-88%) in hepatocellular carcinoma and 64% (25-85%) in cholangiocarcinoma. Conclusion: Differences between MRI-defined liver cancer GTVs and CT-defined GTVs can be substantial and are more common in primary liver cancer.« less

Mixed-function oxygenases, oxidative stress, and chromosomal damage measured in lesser scaup wintering on the Indiana Harbor Canal

USGS Publications Warehouse

Custer, T.W.; Custer, Christine M.; Hines, R.K.; Sparks, D.W.; Melancon, M.J.; Hoffman, D.J.; Bickham, J.W.; Wickliffe, J.K.

2000-01-01

During the winter of 1993-1994, male lesser scaup (Aythya affinis) were collected on the heavily polluted Indiana Harbor Canal, East Chicago, Indiana, and examined for several bioindicators of chemical exposure. Livers were analyzed for activities of three cytochrome P450-associated monooxygenases and four measures of oxidative stress. Blood and spleen were analyzed by flow cytometry for chromosomal damage. In a concurrent study, scaup tissues were analyzed for organic and inorganic contaminants. Ethoxyresorufin-O-dealkylase (EROD) activity in livers of scaup collected in January 1994 was significantly higher than in livers of scaup collected in March 1994 or in livers of reference birds. Three hepatic monooxygenase activities were each significantly correlated with polycyclic aromatic hydrocarbon (PAH) concentrations in scaup carcasses. Thiobarbituric acid (TBA) activity in scaup livers was positively correlated with iron, boron, and lead concentrations in livers and polychlorinated biphenyl concentrations in carcasses. TBA activity was negatively correlated with protein-bound thiol activity and mercury concentrations in livers. The coefficient of variation of DNA content in scaup blood cells was correlated with PAH concentrations in scaup carcasses. This is the first field study with birds to demonstrate a correlation between liver monooxygenase activity and carcass PAH concentrations and to show a direct correlation between PAH concentrations in tissues and somatic chromosomal damage in blood.

Mixed-function oxygenases, oxidative stress, and chromosomal damage measured in lesser scaup wintering on the Indiana Harbor Canal

USGS Publications Warehouse

Custer, T.W.; Custer, Christine M.; Hines, R.K.; Sparks, D.W.; Melancon, M.J.; Hoffman, D.J.; Bickham, J.W.; Wickliffe, J.K.

2000-01-01

During the winter of 1993-1994, male lesser scaup (Aythya alfinis) were collected on the heavily polluted Indiana Harbor Canal, East Chicago, Indiana, and examined for several bioindicators of chemical exposure. Livers were analyzed for activities of three cytochrome P450-associated monooxygenases and four measures of oxidative stress. Blood and spleen were analyzed by flow cytometry for chromosomal damage. In a concurrent study, scaup tissues were analyzed for organic and inorganic contaminants. Ethoxyresomfm-O-dealkylase (EROD) activity in livers of scaup collected in January 1994 was significantly higher than in livers of scaup collected in March 1994 or in livers of reference birds. Three hepatic monooxygenase activities were each significantly correlated with polycyclic aromatic hydrocarbon (PAH) concentrations in scaup carcasses. Thiobarbituric acid (TBA) activity in scaup livers was positively correlated with iron, boron, and lead concentrations in livers and polychlorinated biphenyl concentrations in carcasses. TBA activity was negatively correlated with protein-bound thiol activity and mercury concentrations in livers. The coefficient of variation of DNA content in scaup blood cells was correlated with PAH concentrations in scaup carcasses. This is the first field study with birds to demonstrate a correlation between liver monooxygenase activity and carcass PAH concentrations and to show a direct correlation between PAH concentrations in tissues and somatic chromosomal damage in blood.

[Conversion Therapy Using Etoposide and Cisplatin Chemotherapy for Liver Metastases from Advanced Gastric Mixed Adenoneuroendocrine Carcinoma - A Case Report].

PubMed

Inaba, Yoko; Fujita, Maiko; Ninomiya, Riki; Hashimoto, Daijo

2017-11-01

Gastric mixed adenoneuroendocrine carcinoma(MANEC)with multiple liver metastases is a rare condition with most data being derived from case reports. We present a case with liver metastases from gastric MANEC that respond remarkably to chemotherapy. Sixty-one-year-old male with severe anemia referred to surgical consultation due to advanced gastric cancer with multiple liver metastases. To relieve uncontrollable tumor bleeding, simple distal gastrectomy for symptom palliation was performed. Based on the tentative diagnosis with gastric poorly differentiated adenocarcinoma, a course of TS-1 and oxaliplatin therapy was administrated. Thereafter final diagnosis with neuroendocrine carcinoma with tubular adenocarcinoma was made, and the chemotherapy was switched to etoposide and cisplatin. Follow up abdominal CT scan after the third course of the therapy showed remarkable tumor shrinkages(PR). In anticipation of the chemotherapy effects in the adjuvant setting, we performed liver metastasectomy for curative intent. Two of 6 resected liver specimens showed no viable cancer cells at all (pCR). However, immediately after the surgery, multiple liver metastases developed, and the recurrent masses had kept growing up rapidly. The third line carboplatin and etoposide chemotherapy was given once but was withdrawn because of bone marrow suppression. At the present, the patient is alive with recurrent diseases for 18 months after initial diagnosis.

Retrospective Identification of Herpes Simplex 2 Virus-Associated Acute Liver Failure in an Immunocompetent Patient Detected Using Whole Transcriptome Shotgun Sequencing.

PubMed

Ono, Atsushi; Hayes, C Nelson; Akamatsu, Sakura; Imamura, Michio; Aikata, Hiroshi; Chayama, Kazuaki

2017-01-01

Acute liver failure (ALF) is a severe condition in which liver function rapidly deteriorates in individuals without prior history of liver disease. While most cases result from acetaminophen overdose or viral hepatitis, in up to a third of patients, no clear cause can be identified. Liver transplantation has greatly reduced mortality among these patients, but 40% of patients recover without liver transplantation. Therefore, there is an urgent need for rapid determination of the etiology of acute liver failure. In this case report, we present a case of herpes simplex 2 virus- (HSV-) associated ALF in an immunocompetent patient. The patient recovered without LT, but the presence of HSV was not suspected at the time, precluding more effective treatment with acyclovir. To determine the etiology, stored blood samples were analyzed using whole transcriptome shotgun sequencing followed by mapping to a panel of viral reference sequences. The presence of HSV-DNA in blood samples at the time of admission was confirmed using real-time polymerase chain reaction, and, at the time of discharge, HSV-DNA levels had decreased by a factor of 10 6 . Conclusions. In ALF cases of undetermined etiology, uncommon causes should be considered, especially those for which an effective treatment is available.

A fatal case of hemoperitoneum after ultrasound-guided liver biopsy in a patient with intravascular large B-cell lymphoma.

PubMed

Aoki, Yasuhiro; Takamiya, Masataka; Satoh, Takashi; Fujita, Sachiko; Kato, Hideaki; Maeno, Yoshitaka

2011-07-01

An autopsy case of fatal complication of percutaneous liver biopsy targeting a rare type of large B-cell lymphoma is presented. A 79 year-old man was referred to the hematology unit of a hospital because of anemia with thrombocytopenia and hepatosplenomegaly. Results of inguinal lymph node biopsy were inconclusive. To investigate a mass lesion in the liver visualized by ultrasonography, image-guided liver biopsy was performed following platelet infusion. The patient became unresponsive 6h post procedure because of hypotension due to intraperitoneal hemorrhage of undetermined origin. Autopsy revealed hemoperitoneum but failed to identify any macroscopic intra- or extrahepatic vascular injuries. Histopathological investigation disclosed infiltration of atypical lymphocytes into the systemic organs including the lymph nodes, spleen, liver, and lungs. Prominent hemophagocytosis was also noted. The lymphoma cells were exclusively accumulated within vascular and sinusoidal structures, and diagnosed with immunohistochemistry as Asian variant of intravascular large B-cell lymphoma. Massive blood extravasation was presumed to originate directly from the markedly dilated liver sinusoids filled with erythrocytes, macrophages and tumor cells, under the condition of impaired hemostasis. Although the biopsy was thought to have been correctly performed, this case would be instructive for evaluation of the indications and risks associated with liver biopsy. 2011 Elsevier Ireland Ltd. All rights reserved.

Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

2011-01-01

Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

Combination of tauroursodeoxycholic acid and N-acetylcysteine exceeds standard treatment for acetaminophen intoxication.

PubMed

Paridaens, Annelies; Raevens, Sarah; Colle, Isabelle; Bogaerts, Eliene; Vandewynckel, Yves-Paul; Verhelst, Xavier; Hoorens, Anne; van Grunsven, Leo A; Van Vlierberghe, Hans; Geerts, Anja; Devisscher, Lindsey

2017-05-01

Acetaminophen overdose in mice is characterized by hepatocyte endoplasmic reticulum stress, which activates the unfolded protein response, and centrilobular hepatocyte death. We aimed at investigating the therapeutic potential of tauroursodeoxycholic acid, a hydrophilic bile acid known to have anti-apoptotic and endoplasmic reticulum stress-reducing capacities, in experimental acute liver injury induced by acetaminophen overdose. Mice were injected with 300 mg/kg acetaminophen, 2 hours prior to receiving tauroursodeoxycholic acid, N-acetylcysteine or a combination therapy, and were euthanized 24 hours later. Liver damage was assessed by serum transaminases, liver histology, terminal deoxynucleotidyl transferase dUTP nick end labelling staining, expression profiling of inflammatory, oxidative stress, unfolded protein response, apoptotic and pyroptotic markers. Acetaminophen overdose resulted in a significant increase in serum transaminases, hepatocyte cell death, unfolded protein response activation, oxidative stress, NLRP3 inflammasome activation, caspase 1 and pro-inflammatory cytokine expressions. Standard of care, N-acetylcysteine and, to a lesser extent, tauroursodeoxycholic treatment were associated with significantly lower transaminase levels, hepatocyte death, unfolded protein response activation, oxidative stress markers, caspase 1 expression and NLRP3 levels. Importantly, the combination of N-acetylcysteine and tauroursodeoxycholic acid improved serum transaminase levels, reduced histopathological liver damage, UPR-activated CHOP, oxidative stress, caspase 1 expression, NLRP3 levels, IL-1β levels and the expression of pro-inflammatory cytokines and this to a greater extend than N-acetylcysteine alone. These findings indicate that a combination strategy of N-acetylcysteine and tauroursodeoxycholic acid surpasses the standard of care in acetaminophen-induced liver injury in mice and might represent an attractive therapeutic opportunity for acetaminophen-intoxicated patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater in a mammal than in a reptile.

PubMed Central

Brand, M D; Couture, P; Else, P L; Withers, K W; Hulbert, A J

1991-01-01

Standard metabolic rate is 7-fold greater in the rat (a typical mammal) than in the bearded dragon, Amphibolurus vitticeps (a reptile with the same body mass and temperature). Rat hepatocytes respire 4-fold faster than do hepatocytes from the lizard. The inner membrane of isolated rat liver mitochondrial has a proton permeability that is 4-5-fold greater than the proton permeability of the lizard liver mitochondrial membrane per mg of mitochondrial protein. The greater permeability of rat mitochondria is not caused by differences in the surface area of the mitochondrial inner membrane, but differences in the fatty acid composition of the mitochondrial phospholipids may be involved in the permeability differences. Greater proton permeability of the mitochondrial inner membrane may contribute to the greater standard metabolic rate of mammals. PMID:1850242

Bioaccumulation, oxidative stress and genotoxicity in fish (Channa punctatus) exposed to a thermal power plant effluent.

PubMed

Javed, Mehjbeen; Ahmad, Irshad; Usmani, Nazura; Ahmad, Masood

2016-05-01

Metal bioaccumulation and induction of biomarkers such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH) and DNA damage are potential indicators of stress in Channa punctatus exposed to effluents. In canal water, receiving thermal power plant discharges, Fe and Ni concentrations exceeded the recommended guidelines set by the United Nations Environment Programme Global Environment Monitoring System (UNEPGEMS). Fe was highly bioavailable and accumulated in all organs (liver, kidney, muscle and integument). The highest metal pollution index (MPI) value of 41.2 was observed in kidney and the lowest 13.5 in muscle tissue. LPO, SOD, CAT and GST levels were significantly higher in liver and kidney, whereas GSH levels declined significantly compared to fish from the reference site. Concomitant damage to DNA was observed with significantly higher mean tail length in the exposed fish gill cells (26.5µm) and in liver (20.8µm) compared to reference fish. Therefore, it can be concluded that the thermal power plant effluent had the potential to cause oxidative stress and DNA damage in C. punctatus. Copyright © 2016 Elsevier Inc. All rights reserved.

Using liver enzymes as screening tests to predict mortality risk.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2008-01-01

Determine the relationship between liver function test results (GGT, alkaline phosphatase, AST, and ALT) and all-cause mortality in life insurance applicants. By use of the Social Security Master Death File, mortality was examined in 1,905,664 insurance applicants for whom blood samples were submitted to the Clinical Reference Laboratory. There were 50,174 deaths observed in this study population. Results were stratified by 3 age/sex groups: females, age <60; males, age <60; and all, age 60+. Liver function test values were grouped using percentiles of their distribution in these 3 age/sex groups, as well as ranges of actual values. Using the risk of the middle 50% of the population by distribution as a reference, relative mortality observed for GGT and alkaline phosphatase was linear with a steep slope from very low to relatively high values. Relative mortality was increased at lower values for both AST and ALT. ALT did not predict mortality for values above the middle 50% of its distribution. GGT and alkaline phosphatase are significant predictors of mortality risk for all values. ALT is still useful for triggering further testing for hepatitis, but AST should be used instead to assess mortality risk linked with transaminases.

Biliary tract variations of the left liver with special reference to the left medial sectional bile duct in 500 patients.

PubMed

Furusawa, Norihiko; Kobayashi, Akira; Yokoyama, Takahide; Shimizu, Akira; Motoyama, Hiroaki; Kanai, Keita; Arakura, Norikazu; Yamada, Akira; Kitou, Yoshihiro; Miyagawa, Shin-Ichi

2015-08-01

Among the intrahepatic bile ducts, the biliary system of the left medial sectional bile duct (B4) is known to have relatively complex patterns. The records of 500 patients who had been diagnosed as having hepato-pancreatico-biliary disease were retrospectively studied for anatomical biliary variations of the left liver with special reference to the drainage system of B4 using magnetic resonance images. The left hepatic duct was present in 494 patients (98.8%), whereas it was lacking in 6 patients (1.2%), and these patients exhibited the following B4 confluence patterns: B4 drained into the common hepatic duct in 2 patients (.4%), the right anterior sectional bile duct in 3 patients (.6%), and the right posterior sectional bile duct in 1 patient (.2%). The left hepatic duct was absent more frequently in patients with portal venous variations than in patients with a common branching pattern (8.2% vs .4%, P = .0011). The presently reported data are useful for obtaining a better understanding of the surgical anatomy of the biliary system of the left liver. Copyright © 2015 Elsevier Inc. All rights reserved.

High-frequency ultrasound for monitoring changes in liver tissue during preservation

NASA Astrophysics Data System (ADS)

Vlad, Roxana M.; Czarnota, Gregory J.; Giles, Anoja; Sherar, Michael D.; Hunt, John W.; Kolios, Michael C.

2005-01-01

Currently the only method to assess liver preservation injury is based on liver appearance and donor medical history. Previous work has shown that high-frequency ultrasound could detect ischemic cell death due to changes in cell morphology. In this study, we use high-frequency ultrasound integrated backscatter to assess liver damage in experimental models of liver ischemia. Ultimately, our goal is to predict organ suitability for transplantation using high-frequency imaging and spectral analysis techniques. To examine the effects of liver ischemia at different temperatures, livers from Wistar rats were surgically excised, immersed in phosphate buffer saline and stored at 4 and 20 °C for 24 h. To mimic organ preservation, livers were excised, flushed with University of Wisconsin (UW) solution and stored at 4 °C for 24 h. Preservation injury was simulated by either not flushing livers with UW solution or, before scanning, allowing livers to reach room temperature. Ultrasound images and corresponding radiofrequency data were collected over the ischemic period. No significant increase in integrated backscatter (~2.5 dBr) was measured for the livers prepared using standard preservation conditions. For all other ischemia models, the integrated backscatter increased by 4-9 dBr demonstrating kinetics dependent on storage conditions. The results provide a possible framework for using high-frequency imaging to non-invasively assess liver preservation injury.

Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers.

PubMed

Boesch, C; Ith, M; Jung, B; Bruegger, K; Erban, S; Diamantis, I; Kreis, R; Bär, A

2001-04-01

Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid. Copyright 2001 Academic Press.

Eddy-Current Reference Standard

NASA Technical Reports Server (NTRS)

Ambrose, H. H., Jr.

1985-01-01

Magnetic properties of metallic reference standards duplicated and stabilized for eddy-current coil measurements over long times. Concept uses precisely machined notched samples of known annealed materials as reference standards.

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

PubMed Central

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.

2016-01-01

Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present. PMID:27777888

[Liver enzyme abnormalities among oil refinery workers].

PubMed

Carvalho, Fernando Martins; Silvany Neto, Annibal Muniz; Mendes, João Luiz Barberino; Cotrim, Helma Pinchemel; Nascimento, Ana Lísia Cunha; Lima Júnior, Alberto Soares; Cunha, Tatiana Oliveira Bernardo da

2006-02-01

Occupational exposure typical of an oil refinery may alter liver function among the workers. Thus, the objective of the study was to identify risk factors for liver enzyme abnormalities among oil refinery workers. The workers at an oil refinery in Northeastern Brazil underwent routine annual medical examination from 1982 to 1998. This case-control study investigated all the 150 cases of individuals with simultaneous gamma-glutamyltransferase and alanine aminotransferase abnormalities of at least 10% above reference levels. As controls, 150 workers without any liver enzyme or bilirubin abnormalities since starting to work there were selected. Odds ratios and the respective 95% confidence intervals were calculated from logistic regression models. In all the production sectors, the risk of liver enzyme abnormalities was significantly higher than in the administrative sector (OR=5.7; 95% CI: 1.7-18.4), even when the effects of alcohol, obesity and medical history of hepatitis were controlled for. During the period from 1992 to 1994, 88 out of the 89 cases occurred among workers from the various production sectors. Occupational exposure plays an important role in causing liver enzyme abnormalities among oil refinery workers. This is in addition to the specifically biological and/or behavioral risk factors such as obesity and alcohol consumption.

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

Pediatric living donor liver transplantation for congenital hepatic fibrosis using a mother's graft with von Meyenburg complex: A case report.

PubMed

Yamada, Naoya; Sanada, Yukihiro; Katano, Takumi; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Miki, Atsushi; Sasanuma, Hideki; Urahashi, Taizen; Sakuma, Yasunaru; Mizuta, Koichi

2016-11-28

This is the first report of living donor liver transplantation (LDLT) for congenital hepatic fibrosis (CHF) using a mother's graft with von Meyenburg complex. A 6-year-old girl with CHF, who suffered from recurrent gastrointestinal bleeding, was referred to our hospital for liver transplantation. Her 38-year-old mother was investigated as a living donor and multiple biliary hamartoma were seen on her computed tomography and magnetic resonance imaging scan. The mother's liver function tests were normal and she did not have any organ abnormality, including polycystic kidney disease. LDLT using the left lateral segment (LLS) graft from the donor was performed. The donor LLS graft weighed 250 g; the graft recipient weight ratio was 1.19%. The operation and post-operative course of the donor were uneventful and she was discharged on post-operative day (POD) 8. The graft liver function was good, and the recipient was discharged on POD 31. LDLT using a graft with von Meyenburg complex is safe and useful. Long-term follow-up is needed with respect to graft liver function and screening malignant tumors.

The value of preoperative computed tomography combined with ultrasound in the investigation of small indeterminate liver lesions in patients with colorectal cancer.

PubMed

Abraham-Nordling, Mirna; Öistämö, Emma; Josephson, Thomas; Hjern, Fredrik; Blomqvist, Lennart

2017-11-01

Background Computed tomography (CT) is used routinely for the preoperative detection of colorectal cancer (CRC) metastases. When small indeterminate focal liver lesions are detected that are too small to characterize (TSTC) on CT, additional imaging is usually needed, resulting in a potential delay in obtaining a complete diagnostic work-up. Purpose To determine the diagnostic accuracy of ultrasound (US) of the liver performed in direct conjunction to CT in the preoperative investigation among patients with newly diagnosed CRC when indeterminate liver lesions were found on CT. Material and Methods Preoperative investigations with CT and consecutive US where CT had shown at least one focal liver lesion in 74 patients diagnosed with CRC between June 2009 and February 2012 were retrospectively reviewed. Either histopathological findings or a combination of imaging and clinical follow-up one to three years after surgery was used as the reference. Results Liver metastases were diagnosed with CT/US in 13 out of 74 patients (17.6%). In one patient, a liver cyst was preoperatively regarded as liver metastasis by a combined CT/US. The sensitivity and specificity for the CT with consecutive US procedure was 100% (13/13) and 98.4% (60/61). Conclusion US performed in conjunction with CT in patients with indeterminate focal liver lesions on CT is an accurate work-up for detection of liver metastases in patients with newly diagnosed CRC. Although our results are promising, they cannot be considered safely generalizable to all hospitals.

Rabies vaccine standards: comparison of the 5th and 6th WHO international reference standards to the USDA veterinary reference standard.

PubMed

Hermann, J; Fry, A; Reising, M; Patterson, P; Siev, D; Gatewood, D

2012-11-06

Ensuring rabies vaccines are potent and effective is paramount in preventing transmission of this deadly disease and safeguarding public health. Efficacy of human and veterinary vaccines is ensured by evaluating relative potency estimates of the vaccine compared to a rabies reference standard using the National Institutes of Health (NIH) test. Reference vaccines are based on the International Standard for Rabies Vaccine provided by the World Health Organization (WHO). A comparison study was conducted to determine the relative potency of the 5th WHO, 6th WHO, and United States Department of Agriculture's (USDA) 08-14 reference standards using the NIH test. Results from the study demonstrate that the 6th WHO reference standard is approximately twice as potent as the 5th WHO reference when reconstituted to contain 1 IU per ml. Based on these results, the Center for Veterinary Biologics (CVB) doubled the reconstitution volume of USDA veterinary reference 08-14 from 13 ml to 26 ml, for an initial use dilution of 0.7 IU per ml for use by veterinary biologics manufacturers in the NIH test. This study emphasizes the importance of reference standard calibration for use in the National Institutes of Health test. Published by Elsevier Ltd.

Albumin Dialysis for Liver Failure: A Systematic Review.

PubMed

Tsipotis, Evangelos; Shuja, Asim; Jaber, Bertrand L

2015-09-01

Albumin dialysis is the best-studied extracorporeal nonbiologic liver support system as a bridge or destination therapy for patients with liver failure awaiting liver transplantation or recovery of liver function. We performed a systematic review to examine the efficacy and safety of 3 albumin dialysis systems (molecular adsorbent recirculating system [MARS], fractionated plasma separation, adsorption and hemodialysis [Prometheus system], and single-pass albumin dialysis) in randomized trials for supportive treatment of liver failure. PubMed, Ovid, EMBASE, Cochrane's Library, and ClinicalTrials.gov were searched. Two authors independently screened citations and extracted data on patient characteristics, quality of reports, efficacy, and safety end points. Ten trials (7 of MARS and 3 of Prometheus) were identified (620 patients). By meta-analysis, albumin dialysis achieved a net decrease in serum total bilirubin level relative to standard medical therapy of 8.0 mg/dL (95% confidence interval [CI], -10.6 to -5.4) but not in serum ammonia or bile acids. Albumin dialysis achieved an improvement in hepatic encephalopathy relative to standard medical therapy with a risk ratio of 1.55 (95% CI, 1.16-2.08) but had no effect survival with a risk ratio of 0.95 (95% CI, 0.84-1.07). Because of inconsistency in the reporting of adverse events, the safety analysis was limited but did not demonstrate major safety concerns. Use of albumin dialysis as supportive treatment for liver failure is successful at removing albumin-bound molecules, such as bilirubin and at improving hepatic encephalopathy. Additional experience is required to guide its optimal use and address safety concerns. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Liver attenuation, pericardial adipose tissue, obesity, and insulin resistance: the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

McAuley, Paul A; Hsu, Fang-Chi; Loman, Kurt K; Carr, J Jeffrey; Budoff, Matthew J; Szklo, Moyses; Sharrett, A Richey; Ding, Jingzhong

2011-09-01

Insulin resistance is linked to general and abdominal obesity, but its relation to hepatic lipid content and pericardial adipose tissue is less clear. The purpose of this study was to examine cross-sectional associations of liver attenuation, pericardial adipose tissue, BMI, and waist circumference with insulin resistance. We measured liver attenuation and pericardial adipose tissue using the existing cardiac computed tomography scans in 5,291 individuals free of clinical cardiovascular disease and diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) during the study's baseline visit (2000-2002). Low liver attenuation was defined as the lowest quartile and high pericardial adipose tissue as the upper quartile of volume (cm(3)). We used standard clinical definitions for obesity and abdominal obesity. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA(IR)) index. In multivariate linear regression with all adiposity measures in the model simultaneously, all adiposity measures were significantly (P < 0.0001) associated with insulin resistance: regression coefficients (±s.e.) were 0.31 (±0.02) for low liver attenuation, 0.27 (±0.02) for high pericardial adipose tissue, 0.27 (±0.02) for obesity, and 0.32 (±0.02) for abdominal obesity. We found significant differences (P = 0.003) between standardized liver attenuation and insulin resistance by ethnicity: regression coefficients per 1 s.d. increment were 0.10 ± 0.01 for whites, 0.11 ± 0.02 for Chinese, 0.08 ± 0.2 for blacks, and 0.14 ± 0.01 for Hispanics. Liver attenuation and pericardial adipose tissue were associated with insulin resistance, independent of BMI and waist circumference.

Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post-hepatectomy liver failure

PubMed Central

Kim, Hee Joon; Kim, Choong Young; Park, Eun Kyu; Hur, Young Hoe; Koh, Yang Seok; Kim, Hyun Jong; Cho, Chol Kyoon

2015-01-01

Objectives The actual future liver remnant (aFLR) is calculated as the ratio of remnant liver volume (RLV) to total functional liver volume (TFLV). The standardized future liver remnant (sFLR) is calculated as the ratio of RLV to standard liver volume (SLV). The aims of this study were to compare the aFLR with the sFLR and to determine criteria for safe hepatectomy using computed tomography volumetry and indocyanine green retention rate at 15 min (ICG R15). Methods Medical records and volumetric measurements were obtained retrospectively for 81 patients who underwent right hemi-hepatectomy for malignant hepatic tumours from January 2010 to November 2013. The sFLR was compared with the aFLR, and a ratio of sFLR to ICG R15 as a predictor of postoperative hepatic function was established. Results In patients without cirrhosis, the sFLR showed a stronger correlation with the total serum bilirubin level than the aFLR (R2 = 0.499 versus R2 = 0.239). Post-hepatectomy liver failure developed only in the group with an sFLR of <25%, regardless of ICG R15. In patients with cirrhosis, the aFLR and sFLR had no correlation with postoperative total serum bilirubin. An sFLR : ICG R15 ratio of >1.9 showed 66.7% sensitivity and 100% specificity. Conclusions Regardless of ICG R15, an sFLR of ≥25% in patients without cirrhosis, and an sFLR of ≥25% with an sFLR : ICG R15 ratio of >1.9 in patients with cirrhosis indicate acceptable levels of safety in major hepatectomy. PMID:24964188

A Formula to Calculate Standard Liver Volume Using Thoracoabdominal Circumference.

PubMed

Shaw, Brian I; Burdine, Lyle J; Braun, Hillary J; Ascher, Nancy L; Roberts, John P

2017-12-01

With the use of split liver grafts as well as living donor liver transplantation (LDLT) it is imperative to know the minimum graft volume to avoid complications. Most current formulas to predict standard liver volume (SLV) rely on weight-based measures that are likely inaccurate in the setting of cirrhosis. Therefore, we sought to create a formula for estimating SLV without weight-based covariates. LDLT donors underwent computed tomography scan volumetric evaluation of their livers. An optimal formula for calculating SLV using the anthropomorphic measure thoracoabdominal circumference (TAC) was determined using leave-one-out cross-validation. The ability of this formula to correctly predict liver volume was checked against other existing formulas by analysis of variance. The ability of the formula to predict small grafts in LDLT was evaluated by exact logistic regression. The optimal formula using TAC was determined to be SLV = (TAC × 3.5816) - (Age × 3.9844) - (Sex × 109.7386) - 934.5949. When compared to historic formulas, the current formula was the only one which was not significantly different than computed tomography determined liver volumes when compared by analysis of variance with Dunnett posttest. When evaluating the ability of the formula to predict small for size syndrome, many (10/16) of the formulas tested had significant results by exact logistic regression, with our formula predicting small for size syndrome with an odds ratio of 7.94 (95% confidence interval, 1.23-91.36; P = 0.025). We report a formula for calculating SLV that does not rely on weight-based variables that has good ability to predict SLV and identify patients with potentially small grafts.

[Brain oedema and acute liver failure].

PubMed

Spahr, L

2003-04-01

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Direct calibration of a reference standard against the air kerma strength primary standard, at 192Ir HDR energy.

PubMed

Rajan, K N Govinda; Selvam, T Palani; Bhatt, B C; Vijayam, M; Patki, V S; Vinatha; Pendse, A M; Kannan, V

2002-04-07

The primary standard of low air kerma rate sources or beams, maintained at the Radiological Standards Laboratory (RSL) of the Bhabha Atomic Research Centre (BARC), is a 60 cm3 spherical graphite ionization chamber. A 192Ir HDR source was standardized at the hospital site in units of air kerma strength (AKS) using this primary standard. A 400 cm3 bakelite chamber, functioning as a reference standard at the RSL for a long period, at low air kerma rates (compared to external beam dose rates), was calibrated against the primary standard. It was seen that the primary standard and the reference standard, both being of low Z, showed roughly the same scatter response and yielded the same calibration factor for the 400 cm3 reference chamber, with or without room scatter. However, any likelihood of change in the reference chamber calibration factor would necessitate the re-transport of the primary standard to the hospital site for re-calibration. Frequent transport of the primary standard can affect the long-term stability of the primary standard, due to its movement or other extraneous causes. The calibration of the reference standard against the primary standard at the RSL, for an industrial type 192Ir source maintained at the laboratory, showed excellent agreement with the hospital calibration, making it possible to check the reference chamber calibration at RSL itself. Further calibration procedures have been developed to offer traceable calibration of the hospital well ionization chambers.

Development and Evaluation of Reference Standards for Image-based Telemedicine Diagnosis and Clinical Research Studies in Ophthalmology

PubMed Central

Ryan, Michael C.; Ostmo, Susan; Jonas, Karyn; Berrocal, Audina; Drenser, Kimberly; Horowitz, Jason; Lee, Thomas C.; Simmons, Charles; Martinez-Castellanos, Maria-Ana; Chan, R.V. Paul; Chiang, Michael F.

2014-01-01

Information systems managing image-based data for telemedicine or clinical research applications require a reference standard representing the correct diagnosis. Accurate reference standards are difficult to establish because of imperfect agreement among physicians, and discrepancies between clinical vs. image-based diagnosis. This study is designed to describe the development and evaluation of reference standards for image-based diagnosis, which combine diagnostic impressions of multiple image readers with the actual clinical diagnoses. We show that agreement between image reading and clinical examinations was imperfect (689 [32%] discrepancies in 2148 image readings), as was inter-reader agreement (kappa 0.490-0.652). This was improved by establishing an image-based reference standard defined as the majority diagnosis given by three readers (13% discrepancies with image readers). It was further improved by establishing an overall reference standard that incorporated the clinical diagnosis (10% discrepancies with image readers). These principles of establishing reference standards may be applied to improve robustness of real-world systems supporting image-based diagnosis. PMID:25954463

Selection of reference standard during method development using the analytical hierarchy process.

PubMed

Sun, Wan-yang; Tong, Ling; Li, Dong-xiang; Huang, Jing-yi; Zhou, Shui-ping; Sun, Henry; Bi, Kai-shun

2015-03-25

Reference standard is critical for ensuring reliable and accurate method performance. One important issue is how to select the ideal one from the alternatives. Unlike the optimization of parameters, the criteria of the reference standard are always immeasurable. The aim of this paper is to recommend a quantitative approach for the selection of reference standard during method development based on the analytical hierarchy process (AHP) as a decision-making tool. Six alternative single reference standards were assessed in quantitative analysis of six phenolic acids from Salvia Miltiorrhiza and its preparations by using ultra-performance liquid chromatography. The AHP model simultaneously considered six criteria related to reference standard characteristics and method performance, containing feasibility to obtain, abundance in samples, chemical stability, accuracy, precision and robustness. The priority of each alternative was calculated using standard AHP analysis method. The results showed that protocatechuic aldehyde is the ideal reference standard, and rosmarinic acid is about 79.8% ability as the second choice. The determination results successfully verified the evaluation ability of this model. The AHP allowed us comprehensive considering the benefits and risks of the alternatives. It was an effective and practical tool for optimization of reference standards during method development. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetics Home Reference: Crigler-Najjar syndrome

MedlinePlus

... from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form ... the body. The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers ...

UPLC/MS MS data of testosterone metabolites in human and zebrafish liver microsomes and whole zebrafish larval microsomes.

PubMed

Saad, Moayad; Bijttebier, Sebastiaan; Matheeussen, An; Verbueken, Evy; Pype, Casper; Casteleyn, Christophe; Van Ginneken, Chris; Maes, Louis; Cos, Paul; Van Cruchten, Steven

2018-02-01

This article represents data regarding a study published in Toxicology in vitro entitled " in vitro CYP-mediated drug metabolism in the zebrafish (embryo) using human reference compounds" (Saad et al., 2017) [1]. Data were acquired with ultra-performance liquid chromatography - accurate mass mass spectrometry (UPLC-amMS). A full spectrum scan was conducted for the testosterone (TST) metabolites from the microsomal stability assay in zebrafish and humans. The microsomal proteins were extracted from adult zebrafish male (MLM) and female (FLM) livers, whole body homogenates of 96 h post fertilization larvae (EM) and a pool of human liver microsomes from 50 donors (HLM). Data are expressed as the abundance from the extracted ion chromatogram of the metabolites.

Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network.

PubMed

Navarro, Victor J; Barnhart, Huiman; Bonkovsky, Herbert L; Davern, Timothy; Fontana, Robert J; Grant, Lafaine; Reddy, K Rajender; Seeff, Leonard B; Serrano, Jose; Sherker, Averell H; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

2014-10-01

The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity caused by conventional medications as well as herbals and dietary supplements (HDS). To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight U.S. referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury caused by HDS. Hepatotoxicity caused by HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments, including death and liver transplantation (LT), were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury caused by bodybuilding HDS, 85 by nonbodybuilding HDS, and 709 by medications. Liver injury caused by HDS increased from 7% to 20% (P < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median, 91 days) in young men, but did not result in any fatalities or LT. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women, and, more frequently, led to death or transplantation, compared to injury from medications (13% vs. 3%; P < 0.05). The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from nonbodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes (death and transplantation). (Hepatology 2014;60:1399-1408). © 2014 by the American Association for the Study of Liver Diseases.

Liver injury from Herbals and Dietary Supplements in the US Drug Induced Liver Injury Network

PubMed Central

Navarro, Victor J.; Barnhart, Huiman; Bonkovsky, Herbert L.; Davern, Timothy; Fontana, Robert J.; Grant, Lafaine; Reddy, K. Rajender; Seeff, Leonard B.; Serrano, Jose; Sherker, Averell H.; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

2014-01-01

Background The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity due to conventional medications as well as herbals and dietary supplements (HDS). Rationale To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight US referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury due to HDS. Hepatotoxicity due to HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments including death and liver transplantation were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury due to bodybuilding HDS, 85 due to non-bodybuilding HDS, and 709 due to medications. Main Results Liver injury due to HDS increased from 7% to 20% (p < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median 91 days) in young men but did not result in any fatalities or liver transplantation. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women and more frequently led to death or transplantation compared to injury from medications (13% vs. 3%, p < 0.05). Conclusions The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from non-bodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes; death and transplantation. PMID:25043597

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors.

PubMed

Bonnesen, Trine Gade; Winther, Jeanette F; Andersen, Klaus K; Asdahl, Peter H; de Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Sällfors Holmqvist, Anna; Madanat-Harjuoja, Laura-Maria; Tryggvadottir, Laufey; Wesenberg, Finn; Heilmann, Carsten; Olsen, Jørgen H; Hasle, Henrik

2018-02-15

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications. © 2017 UICC.

Relationship between Non-Alcoholic Fatty Liver Disease and Breast Cancer.

PubMed

Nseir, William; Abu-Rahmeh, Zuhair; Tsipis, Alex; Mograbi, Julnar; Mahamid, Mahmud

2017-04-01

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis. Breast cancer is now the most common cancer in women and is the leading cause of death from cancer among women. To assess the relationship between NAFLD and newly diagnosed cases of breast cancer. The results of mammography screening examinations in women referred to the Breast Center, Holy Family Hospital, Nazareth during a 4 year period were collected. We identified cases of women who were newly diagnosed with breast cancer and who underwent abdominal computed tomography (CT) within 1 month of the diagnosis. The control group comprised 73 women with normal mammography and breast ultrasonography who underwent abdominal CT within 3 months from the date of the breast cancer screening during the same study period. The control cases were matched by age and body mass index (BMI). We compared the cases with the controls in terms of the presence of diffuse hepatic fatty liver and other known risk factors for breast cancer. Of the 133 women who were screened, 73 with new diagnosis of breast cancer were eligible for the study. NAFLD was found in 33 of the women with breast cancer and in 12 in the control group (45.2% vs.16.4%, respectively, P = 0.002). Multivariate analysis showed NAFLD (odds ratio 2.82, 95% confidence interval 1.2-5.5, P = 0.016) to be associated with breast cancer. NAFLD is associated with breast cancer.

Diagnosis of different liver fibrosis characteristics by blood tests in non-alcoholic fatty liver disease.

PubMed

Calès, Paul; Boursier, Jérôme; Chaigneau, Julien; Lainé, Fabrice; Sandrini, Jeremy; Michalak, Sophie; Hubert, Isabelle; Dib, Nina; Oberti, Frédéric; Bertrais, Sandrine; Hunault, Gilles; Cavaro-Ménard, Christine; Gallois, Yves; Deugnier, Yves; Rousselet, Marie C

2010-10-01

Our aim was to develop an accurate, non-invasive, blood-test-based method for identifying the main characteristics of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Fibrosis was staged according to NASH-CRN and Metavir systems in 226 patients with NAFLD. A fully automated algorithm measured the fractal dimension (FD) and the area of fibrosis (AOF). Independent predictors of diagnostic targets were determined using bootstrap methods. (i) Development. Significant fibrosis defined by NASH-CRN F ≥2 was diagnosed by weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothrombin index [area under the receiver operating characteristic (AUROC)=0.867]; significant fibrosis defined by Metavir F ≥2 was diagnosed by weight, age, glycaemia, AST, ALT, ferritin and platelets (FibroMeter AUROC=0.941, P<0.005). AOF was estimated by the combination of hyaluronic acid, glycaemia, AST, ALT, platelets and prothrombin index ((a) R(2) =0.530), while FD was estimated by hyaluronic acid, glycaemia, AST/ALT, weight and platelets ((a) R(2) =0.529). (ii) Evaluation. Although NASH-CRN was a better system for fibrosis staging, Metavir staging was a better reference for blood test. Thus, the patient rate with predictive values ≥90% by tests was 97.3% with Metavir reference vs. 66.5% with NASH-CRN reference (P<10(-3)). FibroMeter showed a significantly higher AUROC than the NAFLD fibrosis score for significant fibrosis, but not for severe fibrosis or cirrhosis, with both staging systems. Relationships between fibrosis lesions were well reflected by blood tests, e.g., the correlation between histological area and FD of fibrosis (r(s) =0.971, P<10(-3)) was well reflected by the relationship between respective blood tests (r(s) =0.852, P<10(-3)). Different characteristics of fibrosis in NAFLD can be diagnosed and quantified by blood tests with excellent accuracy. © 2010 John Wiley & Sons A/S.

Phantom Study Investigating the Accuracy of Manual and Automatic Image Fusion with the GE Logiq E9: Implications for use in Percutaneous Liver Interventions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burgmans, Mark Christiaan, E-mail: m.c.burgmans@lumc.nl; Harder, J. Michiel den, E-mail: chiel.den.harder@gmail.com; Meershoek, Philippa, E-mail: P.Meershoek@lumc.nl

PurposeTo determine the accuracy of automatic and manual co-registration methods for image fusion of three-dimensional computed tomography (CT) with real-time ultrasonography (US) for image-guided liver interventions.Materials and MethodsCT images of a skills phantom with liver lesions were acquired and co-registered to US using GE Logiq E9 navigation software. Manual co-registration was compared to automatic and semiautomatic co-registration using an active tracker. Also, manual point registration was compared to plane registration with and without an additional translation point. Finally, comparison was made between manual and automatic selection of reference points. In each experiment, accuracy of the co-registration method was determined bymore » measurement of the residual displacement in phantom lesions by two independent observers.ResultsMean displacements for a superficial and deep liver lesion were comparable after manual and semiautomatic co-registration: 2.4 and 2.0 mm versus 2.0 and 2.5 mm, respectively. Both methods were significantly better than automatic co-registration: 5.9 and 5.2 mm residual displacement (p < 0.001; p < 0.01). The accuracy of manual point registration was higher than that of plane registration, the latter being heavily dependent on accurate matching of axial CT and US images by the operator. Automatic reference point selection resulted in significantly lower registration accuracy compared to manual point selection despite lower root-mean-square deviation (RMSD) values.ConclusionThe accuracy of manual and semiautomatic co-registration is better than that of automatic co-registration. For manual co-registration using a plane, choosing the correct plane orientation is an essential first step in the registration process. Automatic reference point selection based on RMSD values is error-prone.« less

SU-D-BRF-04: Digital Tomosynthesis for Improved Daily Setup in Treatment of Liver Lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, H; Jones, B; Miften, M

Purpose: Daily localization of liver lesions with cone-beam CT (CBCT) is difficult due to poor image quality caused by scatter, respiratory motion, and the lack of radiographic contrast between the liver parenchyma and the lesion(s). Digital tomosynthesis (DTS) is investigated as a modality to improve liver visualization and lesion/parenchyma contrast for daily setup. Methods: An in-house tool was developed to generate DTS images using a point-by-point filtered back-projection method from on-board CBCT projection data. DTS image planes are generated in a user defined orientation to visualize the anatomy at various depths. Reference DTS images are obtained from forward projection ofmore » the planning CT dataset at each projection angle. The CBCT DTS image set can then be registered to the reference DTS image set as a means for localization. Contour data from the planning CT's associate RT Structure file and forward projected similarly to the planning CT data. DTS images are created for each contoured structure, which can then be overlaid onto the DTS images for organ volume visualization. Results: High resolution DTS images generated from CBCT projections show fine anatomical detail, including small blood vessels, within the patient. However, the reference DTS images generated from forward projection of the planning CT lacks this level of detail due to the low resolution of the CT voxels as compared to the pixel size in the projection images; typically 1mm-by-1mm-by-3mm (lat, vrt, lng) for the planning CT vs. 0.4mm-by-0.4mm for CBCT projections. Overlaying of the contours onto the DTS image allows for visualization of structures of interest. Conclusion: The ability to generate DTS images over a limited range of projection angles allows for reduction in the amount of respiratory motion within each acquisition. DTS may provide improved visualization of structures and lesions as compared to CBCT for highly mobile tumors.« less

Causes of altered liver function tests - the role of alpha-1 antitrypsin.

PubMed

Stollenwerk, J; Schepke, M; Biecker, E

2016-09-01

Altered liver function tests are a common finding in clinical practice. Our retrospective study aimed to identify the diagnoses in a non-selected cohort of patients with altered liver tests and to investigate whether alpha-1 antitrypsin genotyping should be part of the diagnostic workup. 501 patients who were admitted to our outpatient clinic for further evaluation of altered liver function tests were included in the study. The patients underwent a standardized diagnostic program with history taking, physical examination, laboratory tests and ultrasonography. Liver biopsy was performed if appropriate. More than 50 % of the patients had nonalcoholic fatty liver disease. Alcoholic and drug-induced liver injury were found in 8.6 % and 7 % of patients, respectively. Chronic hepatitis B and C, autoimmune liver disease and inherited causes of liver disease made up for approximately 16 % of the diagnoses. The remaining patients were diagnosed with kryptogenic liver disease or had miscellaneous diagnoses. In 3.7 % of the genotyped patients, the alpha-1 antitrypsin genotype PiMZ was found. Nonalcoholic fatty liver disease is nowadays the most frequent cause of altered liver tests. Alcoholic liver disease might be underrepresented in our study since these patients less often seek medical attention or the diagnosis is already made by the primary care physician. Drug-induced liver injury was found in more patients than expected and might therefore be underdiagnosed in practice. The alpha-1 antitrypsin genotype PiMZ was found in absence of other possible causes of liver disease, indicating that the PiMZ genotype is itself a risk factor for liver disease. Genotyping for alpha-1 antitrypsin should therefore be done when other causes for altered liver function tests have been ruled out. © Georg Thieme Verlag KG Stuttgart · New York.

[Contents of calcium, phosphorus and aluminum in central nervous system, liver and kidney of rabbits with experimental atherosclerosis--scavenger effects of vinpocetine on the deposition of elements].

PubMed

Yasui, M; Yano, I; Ota, K; Oshima, A

1990-04-01

The aims in this study were designed to clarify the contents of calcium (Ca), phosphorus (P) and aluminum (Al) in central nervous system (CNS), liver and kidney of rabbits with atherosclerosis experimentally induced by cholesterol-rich diet, and investigate scavenger effect of 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine) on the deposition of these elements in CNS and soft tissues of experimental atherosclerosis. Sixteen male rabbits were divided into 4 groups. Each group was fed with standard diet (Group A), standard diet containing 1.5% cholesterol (Group B), standard diet containing 1.5% cholesterol plus oral administration of 3 mg/kg/day vinpocetine (Group C), and standard diet containing 1.5% cholesterol plus administration of 10 mg/kg/day vinpocetine (Group D). After 3 months' feeding, experimental atherosclerosis was produced with a modified method of Kritchevsky et al in rabbits of Groups B, C and D. Blood was collected by cardiocentesis under the anesthesia of ether and then rabbits sacrificed to remove CNS and other tissues. The blood was stood for 1 hour at room temperature and separated by centrifugation at 3000 rpm for 10 min to determine serum total cholesterol, phospholipids, HDL-cholesterol, peroxide lipid, NEFA and calcium levels. Ca, P and Al contents in the frontal lobe, pons, cerebellum, spinal cord, liver and kidney were determined by neutron activation analysis. Ca contents of CNS, liver and kidney in Group B significantly increased than those of Group A (p less than 0.01), and significantly decreased in Groups C and D compared with those of Group B (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Application of high-performance liquid chromatography to the determination of glyoxylate synthesis in chick embryo liver.

PubMed

Qureshi, A A; Elson, C E; Lebeck, L A

1982-11-19

The isolation and identification of three major alpha-keto end products (glyoxylate, pyruvate, alpha-ketoglutarate) of the isocitrate lyase reaction in 18-day chick embryo liver have been described. This was accomplished by the separation of these alpha-keto acids as their 2,4-dinitrophenylhydrazones (DNPHs) by high-performance liquid chromatography (HPLC). The DNPHs of alpha-keto acids were eluted with an isocratic solvent system of methanol-water-acetic acid (60:38.5:1.5) containing 5 mM tetrabutylammonium phosphate from a reversed-phase ultrasphere C18 (IP) and from a radial compression C18 column. The separation can be completed on the radial compression column within 15-20 min as compared to 30-40 min with a conventional reversed-phase column. Retention times and peak areas were integrated for both the assay samples and reference compounds. A relative measure of alpha-keto acid in the peak was calculated by comparison with the standard. The identification of each peak was done on the basis of retention time matching, co-chromatography with authentic compounds, and stopped flow UV-VIS scanning between 240 and 440 nm. Glyoxylate represented 5% of the total product of the isocitrate lyase reaction. Day 18 parallels the peak period of embryonic hepatic glycogenesis which occurs at a time when the original egg glucose reserve has been depleted.

15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...

15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...

15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...

15 CFR 200.105 - Standard reference data.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., PROCEDURES, AND FEES § 200.105 Standard reference data. Data on the physical and chemical properties of the... application in research, development, engineering design, and commerce. The Office of Standard Reference Data... Physical and Chemical Reference Data, published jointly with the American Chemical Society and the American...

Development and validation of a UPLC-MS/MS method for the simultaneous determination of paritaprevir and ritonavir in rat liver.

PubMed

Ocque, Andrew J; Hagler, Colleen E; Difrancesco, Robin; Woolwine-Cunningham, Yvonne; Bednasz, Cindy J; Morse, Gene D; Talal, Andrew H

2016-07-01

Determination of paritaprevir and ritonavir in rat liver tissue samples. We successfully validated a UPLC-MS/MS method to measure paritaprevir and ritonavir in rat liver using deuterated internal standards (d8-paritapervir and d6-ritonavir). The method is linear from 20 to 20,000 and 5 to 10,000 pg on column for paritaprevir and ritonavir, respectively, and is normalized per milligram tissue. Interday and intraday variability ranged from 0.591 to 5.33% and accuracy ranged from -6.68 to 10.1% for quality control samples. The method was then applied to the measurement of paritaprevir and ritonavir in rat liver tissue samples from a pilot study. The validated method is suitable for measurement of paritaprevir and ritonavir within rat liver tissue samples for PK studies.

Alternative Cell Sources to Adult Hepatocytes for Hepatic Cell Therapy.

PubMed

Pareja, Eugenia; Gómez-Lechón, María José; Tolosa, Laia

2017-01-01

Adult hepatocyte transplantation is limited by scarce availability of suitable donor liver tissue for hepatocyte isolation. New cell-based therapies are being developed to supplement whole-organ liver transplantation, to reduce the waiting-list mortality rate, and to obtain more sustained and significant metabolic correction. Fetal livers and unsuitable neonatal livers for organ transplantation have been proposed as potential useful sources of hepatic cells for cell therapy. However, the major challenge is to use alternative cell sources for transplantation that can be derived from reproducible methods. Different types of stem cells with hepatic differentiation potential are eligible for generating large numbers of functional hepatocytes for liver cell therapy to treat degenerative disorders, inborn hepatic metabolic diseases, and organ failure. Clinical trials are designed to fully establish the safety profile of such therapies and to define target patient groups and standardized protocols.

Liver Rapid Reference Set Application: Hiro Yamada - Wako (2011) — EDRN Public Portal

Cancer.gov

Measure clinical effectiveness of AFP-L3 and DCP for early detection of HCC in patient samples collected prospectively during surveillance. However since such samples are not readily available in the USA the reference set samples are well characterized and studied, gaining access to these samples will allow Wako to quickly measure clinical effectiveness of AFP-L3 and DCP in detecting early HCC.

In vitro metabolism of [14C]-benalaxyl in hepatocytes of rats, dogs and humans.

PubMed

Nallani, Gopinath C; ElNaggar, Shaaban F; Shen, Li; Chandrasekaran, Appavu

2017-03-01

The in vitro comparative animal metabolism study is now a data requirement under EU Directive 1107/2009 for registration of plant protection products. This type of study helps determine the extent of metabolism of a chemical in each surrogate species and whether any unique human metabolite(s) are formed. In the present study, metabolism of racemic [ 14 C]-benalaxyl, a fungicide was investigated in cryopreserved rat, dog and human hepatocytes. The metabolites generated were identified/characterized by LC/MS/MS with radiometric detection and comparison with reference standards. [ 14 C]-glucuronide conjugates of benalaxyl metabolites in rat, dog and human hepatocytes were confirmed via additional experiments in which known reference standards were incubated with dog liver microsomes in the presence of UDPGA. After 4 h of incubation, benalaxyl was extensively metabolized in all the species with the following trend: dog (100%) > human (86%) > rat (75%). In all species, the major metabolic pathways consisted of hydroxylation of the methyl group in the xylene moiety to 2-hydroxymethyl-benalaxyl, further oxidation to its carboxylic acid analogue (benalaxyl-2-benzoic acid), and hydrolysis of the methyl ester to yield benalaxyl acid or 2-hydroxymethyl benalaxyl acid. In addition, glucuronidation of phase I metabolites occurred in all species, to a higher extent in dog hepatocytes in which 2-hydroxymethyl-benalaxyl-glucuronide conjugate constituted the most significant metabolite. No major unique metabolite was observed in human hepatocytes. Also, benalaxyl did not undergo stereo-selective metabolism in rat or human hepatocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Insights on augmenter of liver regeneration cloning and function

PubMed Central

Gatzidou, Elisavet; Kouraklis, Gregory; Theocharis, Stamatios

2006-01-01

Hepatic stimulator substance (HSS) has been referred to as a liver-specific but species non-specific growth factor. Gradient purification and sequence analysis of HSS protein indicated that it contained the augmenter of liver regeneration (ALR), also known as hepatopoietin (HPO). ALR, acting as a hepatotrophic growth factor, specifically stimulated proliferation of cultured hepatocytes as well as hepatoma cells in vitro, promoted liver regeneration and recovery of damaged hepatocytes and rescued acute hepatic failure in vivo. ALR belongs to the new Erv1/Alr protein family, members of which are found in lower and higher eukaryotes from yeast to man and even in some double-stranded DNA viruses. The present review article focuses on the molecular biology of ALR, examining the ALR gene and its expression from yeast to man and the biological function of ALR protein. ALR protein seems to be non-liver-specific as was previously believed, increasing the necessity to extend research on mammalian ALR protein in different tissues, organs and developmental stages in conditions of normal and abnormal cellular growth. PMID:16937489

The protective effect of Nigella sativa against liver injury: a review.

PubMed

Mollazadeh, Hamid; Hosseinzadeh, Hossein

2014-12-01

Nigella sativa (Family Ranunculaceae) is a widely used medicinal plant throughout the world. N. sativa is referred in the Middle East as a part of an overall holistic approach to health. Pharmacological properties of N. sativa including immune stimulant, hypotensive, anti-inflammatory, anti-cancer, antioxidant, hypoglycemic, spasmolytic and bronchodilator have been shown. Reactive oxygen species (ROS) and oxidative stress are known as the major causes of many diseases such as liver injury and many substances and drugs can induce oxidative damage by generation of ROS in the body. Many pharmacological properties of N. sativa are known to be attributed to the presence of thymoquinone and its antioxidant effects. Thymoquinone protects liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and glutathione level, radical scavengering, increasing the activity of quinone reductase, catalase, superoxide dismutase and glutathione transferase, inhibition of NF-κB activity and inhibition of both cyclooxygenase and lipoxygenase. Therefore, this review aimed to highlight the roles of ROS in liver diseases and the mechanisms of N. sativa in prevention of liver injury.

Polyphenolic content and antioxidant properties of Moringa oleifera leaf extracts and enzymatic activity of liver from goats supplemented with Moringa oleifera leaves/sunflower seed cake.

PubMed

Moyo, B; Oyedemi, S; Masika, P J; Muchenje, V

2012-08-01

The study investigated antioxidant potency of Moringa oleifera leaves in different in vitro systems using standard phytochemical methods. The antioxidative effect on the activities of superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO) and reduced glutathione (GSH) were investigated in goats supplemented with M. oleifera (MOL) or sunflower seed cake (SC). The acetone extract had higher concentrations of total flavonoids (295.01 ± 1.89 QE/g) followed by flavonols (132.74 ± 0.83 QE/g), phenolics (120.33 ± 0.76 TE/g) and then proanthocyanidins (32.59 ± 0.50 CE/g) than the aqueous extract. The reducing power of both solvent extracts showed strong antioxidant activity in a concentration dependent manner. The acetone extract depicted higher percentage inhibition against DPPH, ABTS and nitric oxide radicals which were comparable with reference standard antioxidants (vitamin C and BHT). MOL increased the antioxidant activity of GSH (186%), SOD (97.8%) and catalase (0.177%). Lipid peroxidation was significantly reduced by MOL. The present study suggests that M. oleifera could be a potential source of compounds with strong antioxidant potential. Copyright © 2012 Elsevier Ltd. All rights reserved.

Liver transplantation in Asia: past, present and future.

PubMed

Ng, Kelvin K; Lo, Chung Mau

2009-04-01

With the technical advances and improvements in perioperative management and immunosuppressants, liver transplantation is the standard treatment for patients with end-stage liver diseases. In Asia, a shortage of deceased donor liver grafts is the universal problem to be faced with in all transplant centres. Many surgical innovations are then driven to counteract this problem. This review focuses on 3 issues that denote the development of liver transplantation in Asian countries. These include living donor liver transplantation (LDLT), split liver transplantation (SLT) and liver transplantation for hepatocellular carcinoma (HCC). Minimal graft weight, types of liver graft to donate and the inclusion of the middle hepatic vein with the graft are the main issues to be established in LDLT. The rapid growth and wide dissemination of LDLT has certainly alleviated the supply-and-demand problem of liver grafts in Asia. SLT is another attractive approach. Technical expertise, donor selection and graft allocation are the main determinants for its success. Liver transplantation plays a key role in the management of HCC in Asia. LDLT would be the main strategy in this aspect. The issue of extending the selection criteria for HCC patients for LDLT is still controversial. On the whole, future developments to increase the donor pool for the expanding recipient need in Asia would involve transplantation from non-heart beating donor and ABO incompatible transplantation.