Dietary cholesterol, female gender and n-3 fatty acid deficiency are more important factors in the development of non-alcoholic fatty liver disease than the saturation index of the fat

<p>Abstract</p> <p>Background</p> <p>The central feature of NAFLD is a disturbed fatty-acid metabolism with hepatic lipid accumulation. However, the factors that determine the severity of NAFLD, including the role of nutrition, gender, and plasma lipid levels, remain to be determined.</p> <p>Methods</p> <p>High-fat diets (42 en% fat), containing 0.2% cholesterol, were fed to male and female wild-type and hyperlipidemic <it>APOE2ki </it>C57BL/6J mice for three weeks. The fats were, in order of decreasing saturation, fractionated palm fat (fPF; ~95%), cocoa butter (CB; ~60%), olive oil (OO; ~15%), sunflower oil (SO; ~12%), and high-oleic-acid sunflower oil (hoSO; ~7%). Plasma and liver triglycerides (concentration and composition), liver inflammation (<it>Ccl2</it>, <it>Cd68</it>, <it>Tnf-α </it>mRNA), and infiltration of macrophages (Cd68, Cd11b immunohistochemistry) and neutrophils (Mpo) were quantified.</p> <p>Results</p> <p>Addition of cholesterol to a low-fat diet decreased plasma HDL and increased (V)LDL levels in APOE2ki mice. Plasma cholesterol levels in female, but not male APOE2ki mice correlated significantly with inflammation. Kupffer cells of inflamed livers were swollen. Wild-type mice refused the highly saturated fPF diet. The high-fat CB, OO, and SO diets induced hyperglycemia and a 2-fold increase in hepatic fat content in male, but not female wild-type mice (in females, hepatic fat content was similar to that in males fed a high-fat diet). All high-fat diets induced macrovesicular setatosis. APOE2ki mice were protected against high-fat diet-induced steatosis and hyperglycemia, except when fed a hoSO diet. This diet caused a 5-fold increase in liver triglyceride and mead-acid content, and an increased expression of lipogenic genes, suggesting a deficiency in poly-unsaturated fatty acids. Irrespective of the composition of the high-fat diet, oleic acid was the main triglyceride component of liver fat in wild-type and APOE2ki mouse livers. Liver inflammation was dependent on genotype (APOE2ki > wild type), gender (female > male), and cholesterol content (high > low) of the diet, but not on dietary fat composition.</p> <p>Conclusions</p> <p>Dietary cholesterol plays a determining, independent role in inflammation, especially in female mice. The fatty-acid saturation of the diet hardly affected hepatic steatosis or inflammation.</p

Exercise-Induced splanchnic hypoperfusion results in gut dysfunction in healthy men

Background Splanchnic hypoperfusion is common in various pathophysiological conditions and often considered to lead to gut dysfunction. While it is known that physiological situations such as physical exercise also result in splanchnic hypoperfusion, the consequences of flow redistribution at the expense of abdominal organs remained to be determined. This study focuses on the effects of splanchnic hypoperfusion on the gut, and the relationship between hypoperfusion, intestinal injury and permeability during physical exercise in healthy men. Methods and Findings Healthy men cycled for 60 minutes at 70% of maximum workload capacity. Splanchnic hypoperfusion was assessed using gastric tonometry. Blood, sampled every 10 minutes, was analyzed for enterocyte damage parameters (intestinal fatty acid binding protein (I-FABP) and ileal bile acid binding protein (I-BABP)). Changes in intestinal permeability were assessed using sugar probes. Furthermore, liver and renal parameters were assessed. Splanchnic perfusion rapidly decreased during exercise, reflected by increased gapg-apCO2 from −0.85±0.15 to 0.85±0.42 kPa (p < 0.001). Hypoperfusion increased plasma I-FABP (615±118 vs. 309±46 pg/ml, p < 0.001) and I-BABP (14.30±2.20 vs. 5.06±1.27 ng/ml, p < 0.001), and hypoperfusion correlated significantly with this small intestinal damage (rS = 0.59; p < 0.001). Last of all, plasma analysis revealed an increase in small intestinal permeability after exercise (p < 0.001), which correlated with intestinal injury (rS = 0.50; p < 0.001). Liver parameters, but not renal parameters were elevated. Conclusions Exercise-induced splanchnic hypoperfusion results in quantifiable small intestinal injury. Importantly, the extent of intestinal injury correlates with transiently increased small intestinal permeability, indicating gut barrier dysfunction in healthy individuals. These physiological observations increase our knowledge of splanchnic hypoperfusion sequelae, and may help to understand and prevent these phenomena in patients

Nodular Regenerative Hyperplasia Secondary to Neoadjuvant Chemotherapy for Colorectal Liver Metastases

Liver resection is the only curative treatment for patients with colorectal liver metastases (CLMs). Neoadjuvant chemotherapy can improve resectability but has a potential harmful effect on the nontumorous liver. Patients with chemotherapy-induced hepatic injury undergoing liver surgery have higher risks of post-resectional morbidity. We present two cases of patients without pre-existent liver disease treated with oxaliplatin-based chemotherapy followed by surgical resection of their CLMs. Their intra-operative liver specimen showed morphologic abnormalities characteristic of nodular regenerative hyperplasia (NRH). NRH led to portal hypertension in both patients that resulted in deleterious post-resectional complications and death of one patient. Interestingly, the other patient underwent two repeat nonanatomic liver resections because of recurrent CLMs. The intra-operative liver specimen still showed signs of NRH and sinusoidal congestion, but the post-resectional courses were uneventful. Nevertheless, caution is recommended in patients with suspected NRH. Careful volumetric analysis should guide the operative strategy. When future remnant liver volume is regarded insufficient, portal vein embolization or restrictive surgery should be considered

Myosteatosis predicts survival after surgery for periampullary cancer::a novel method using MRI

Background: Myosteatosis, characterized by inter-and intramyocellular fat deposition, is strongly related to poor overall survival after surgery for periampullary cancer. It is commonly assessed by calculating the muscle radiation attenuation on computed tomography (CT) scans. However, since magnetic resonance imaging (MRI) is replacing CT in routine diagnostic work-up, developing methods based on MRI is important. We developed a new method using MRI-muscle signal intensity to assess myosteatosis and compared it with CT-muscle radiation attenuation.Methods: Patients were selected from a prospective cohort of 236 surgical patients with periampullary cancer. The MRI-muscle signal intensity and CT-muscle radiation attenuation were assessed at the level of the third lumbar vertebra and related to survival.Results: Forty-seven patients were included in the study. Inter-observer variability for MRI assessment was low (R-2 = 0.94). MRI-muscle signal intensity was associated with short survival: median survival 9.8 (95%-CI: 1.5-18.1) vs. 18.2 (95%-CI: 10.7-25.8) months for high vs. low intensity, respectively (p = 0.038). Similar results were found for CT-muscle radiation attenuation (low vs. high radiation attenuation: 10.8 (95%-CI: 8.5-13.1) vs. 15.9 (95%-CI: 10.2-21.7) months, respectively; p = 0.046). MRI-signal intensity correlated negatively with CT-radiation attenuation (r=-0.614, p &lt;0.001).Conclusions: Myosteatosis may be adequately assessed using either MRI-muscle signal intensity or CT-muscle radiation attenuation.</p

Paneth Cell Alterations During Ischemia-reperfusion, Follow-up, and Graft Rejection After Intestinal Transplantation

BACKGROUND Ischemia-reperfusion (IR) injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PC) are crucial for epithelial immune defense and highly vulnerable to IR injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection. Moreover, we investigated whether PC loss was associated with impaired graft homeostasis. METHODS Endoscopic biopsies, collected according to center-protocol and at rejection episodes, were retrospectively included (n=28 ITx, n=119 biopsies) Biopsies were immunohistochemically co-stained for PC (lysozyme) and apoptosis, and PC/crypt and lysozyme intensity were scored. RESULTS We observed a decrease in PC/crypt and lysozyme intensity in the first week after ITx (W1) compared to T0. There was a tendency towards a larger decline in PC/crypt (p=0.08) and lysozyme intensity (p=0.08) in W1 in patients who later developed rejection compared to patients without rejection. Follow-up biopsies showed that the PC number recovered, whereas lysozyme intensity remained reduced. This persisting innate immune defect may contribute to the well-known vulnerability of the intestine to infection. There was no clear evidence that PC were affected throughout rejection. CONCLUSION This study revealed a transient fall in PC numbers in the early post-ITx period, but a permanent reduction in lysozyme intensity following ITx. Further research is needed to determine the potential clinical impact of PC impairment after ITx

Prospective Volumetric Assessment of the Liver on a Personal Computer by Nonradiologists Prior to Partial Hepatectomy

Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background A small remnant liver volume is an important risk factor for posthepatectomy liver failure. ImageJ and OsiriX Ò are both free, open-source image processing software packages. The aim of the present study was to compare ImageJ and OsiriX Ò in performing prospective computed tomography (CT) volumetric analysis of the liver on a personal computer (PC) in patients undergoing major liver resection. Methods Patients scheduled for a right hemihepatectomy were eligible for inclusion. Two surgeons and one surgical trainee measured volumes of total liver, tumor, and future resection specimen prospectively with ImageJ and OsiriX Ò. A radiologist also measured these volumes with CT scanner-linked Aquarius iNtuition Ò software. Resection volumes were compared with the actual weights of the live

Liver Volumetry Plug and Play: Do It Yourself with ImageJ

AB - 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 (r(2) = 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 resectio

Virtual Liver Resection and Volumetric Analysis of the Future Liver Remnant using Open Source Image Processing Software

Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background After extended liver resection, a remnant liver that is too small can lead to postresection liver failure. To reduce this risk, preoperative evaluation of the future liver remnant volume (FLRV) is critical. The open-source OsiriX Ò PAC software system can be downloaded for free and used by nonradiologists to calculate liver volume using a stand-alone Apple computer. The purpose of this study was to assess the accuracy of OsiriX Ò CT volumetry for predicting liver resection volume and FLVR in patients undergoing partial hepatectomy. Methods Preoperative contrast-enhanced liver CT scans of patients who underwent partial hepatectomy were Joost R. van der Vorst and Ronald M. van Dam contributed equally to the study and the manuscript. These authors share first authorship. J. R. van der Vorst R. M. van Dam (&amp;

Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

Contains fulltext : 51690.pdf (publisher's version ) (Closed access)BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection. METHODS: Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured. RESULTS: During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTalpha levels. Hepatocyte injury was followed by an inflammatory response. CONCLUSIONS: This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand