Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C

BACKGROUND: Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)-related steatosis. The MTP -493G/T polymorphism may promote liver fat accumulation, but its role in HCV-related steatosis is still unclear. METHODS: Two hundred ninety-eight CHC patients were studied and genotyped for MTP -493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup. RESULTS: Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV-3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2-3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non-3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22-3.86; P=0.008). Moreover, TT carriers had higher high-density lipoprotein (65.6+/-14.6 vs 56.1+/-16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80+/-0.3 vs 1.60+/-0.3 g/L; P=0.005) levels than G allele carriers. CONCLUSIONS: Chronic hepatitis C patients with the MTP -493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non-3 patients.

Extracts of Lindera obtusiloba induce antifibrotic effects in hepatic stellate cells via suppression of a TGF-beta-mediated profibrotic gene expression pattern

Liver fibrosis is characterized by high expression of the key profibrogenic cytokine transforming growth factor (TGF)-beta and the natural tissue inhibitor of metalloproteinases (TIMP)-1, leading to substantial accumulation of extracellular matrix. Liver fibrosis originates from various chronic liver diseases, such as chronic viral hepatitis that, to date, cannot be treated sufficiently. Thus, novel therapeutics, for example, those derived from Oriental medicine, have gained growing attention. In Korea, extracts prepared from Lindera obtusiloba are used for centuries for treatment of inflammation, improvement of blood circulation and prevention of liver damage, but experimental evidence of their efficacy is lacking. We studied direct antifibrotic effects in activated hepatic stellate cells (HSCs), the main target cell in the fibrotic liver. L. obtusiloba extract (135 mug/ml) reduced the de novo DNA synthesis of activated rat and human HSCs by about 90%, which was not accompanied by cytotoxicity of HSC, primary hepatocytes and HepG2 cells, pointing to induction of cellular quiescence. As determined by quantitative polymerase chain reaction, simultaneous treatment of HSCs with TGF-beta and L. obtusiloba extract resulted in reduction of TIMP-1 expression to baseline level, disruption of the autocrine loop of TGF-beta autoinduction and increased expression of fibrolytic matrix metalloproteinase (MMP)-3. In addition, L. obtusiloba reduced gelatinolytic activity of HSC by interfering with profibrogenic MMP-2 activity. Since L. obtusiloba extract prevented intracellular oxidative stress experimentally induced by tert-butylhydroperoxide, we concluded that the direct antifibrotic effect of L. obtusiloba extract might be mediated by antioxidant activity. Thus, L. obtusiloba, traditionally used in Oriental medicine, may complement treatment of chronic liver disease.

Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion during liver regeneration in mice

Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.

Lateral meniscal cyst causing common peroneal palsy

Lateral meniscal cysts are relatively common, but only in rare instances do they cause common peroneal nerve irritation. There are, we believe, no cases reported in which both the sensory and motor functions of the nerve have been compromised. We present a case of a lateral meniscal cyst that became palpable and led to symptoms of numbness and weakness in the distribution of the common peroneal nerve. The MRI findings were of an oblique tear of the lateral meniscus with an associated multiloculated meniscal cyst that coursed behind the biceps tendon before encroaching on the common peroneal nerve. Surgical resection confirmed the tract as located on the MRI and histology confirmed the mass to be a synovial cyst. Resection of the cyst and arthroscopic excision of the meniscal tear led to resolution of the symptoms in 3 months.

Surgical approach for synovial cyst of the atlantoaxial joint: a case report and review of the literature

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: We describe the first case of a synovial cyst arising from pseudarthrosis of a previous dens fracture. The literature is reviewed and etiological, diagnostic, and therapeutic options of atlantoaxial cysts are discussed. SUMMARY OF BACKGROUND DATA: Symptomatic synovial cysts of the atlantoaxial joint are rare. To the authors' knowledge only 24 cases have been reported.A 60-year-old patient presented with bilateral hand numbness, quadrihyperreflexia, and gait deterioration. Magnetic resonance imaging of the cervical spine disclosed a cystic mass located at the transverse ligament of dens axis causing bulbomedullary compression. METHODS: Surgery was performed via transoral image guided approach. The ventral atlas arch, dens, transverse ligament, tectorial membrane, and the compressing cyst were removed, followed by a C0-C3 fusion. RESULTS: Two months postsurgery the patient recovered completely from the cervical myelopathy with transient remnant dysparesthesia of the finger tips. CONCLUSION: Magnetic resonance imaging findings are not specific enough to establish a preoperative diagnosis. Radical resection via image-guided transoral route followed by posterior fusion allows complete resection of the cystic lesion and results in excellent long-term decompression.

Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis

The vitronectin receptor integrin alphavbeta3 promotes angiogenesis by mediating migration and proliferation of endothelial cells, but also drives fibrogenic activation of hepatic stellate cells (HSCs) in vitro. Expecting antifibrotic synergism, we studied the effect of alphavbeta3 inhibition in two in vivo models of liver fibrogenesis. Liver fibrosis was induced in rats by way of bile duct ligation (BDL) for 6 weeks or thioacetamide (TAA) injections for 12 weeks. A specific alphavbeta3 (alphavbeta5) inhibitor (Cilengitide) was given intraperitoneally twice daily at 15 mg/kg during BDL or after TAA administration. Liver collagen was determined as hydroxyproline, and gene expression was quantified by way of quantitative polymerase chain reaction. Liver angiogenesis, macrophage infiltration, and hypoxia were assessed by way of CD31, CD68 and hypoxia-inducible factor-1alpha immunostaining. Cilengitide decreased overall vessel formation. This was significant in portal areas of BDL and septal areas of TAA fibrotic rats and was associated with a significant increase of liver collagen by 31% (BDL) and 27% (TAA), and up-regulation of profibrogenic genes and matrix metalloproteinase-13. Treatment increased gamma glutamyl transpeptidase in both models, while other serum markers remained unchanged. alphavbeta3 inhibition resulted in mild liver hypoxia, as evidenced by up-regulation of hypoxia-inducible genes. Liver infiltration by macrophages/Kupffer cells was not affected, although increases in tumor necrosis factor alpha, interleukin-18, and cyclooxygenase-2 messenger RNA indicated modest macrophage activation. CONCLUSION: Specific inhibition of integrin alphavbeta3 (alphavbeta5) in vivo decreased angiogenesis but worsened biliary (BDL) and septal (TAA) fibrosis, despite its antifibrogenic effect on HSCs in vitro. Angiogenesis inhibitors should be used with caution in patients with hepatic fibrosis.

Association of gastroschisis and choledochal cyst

Two infants are described who presented in the neonatal period with a direct hyperbilirubinemia. This was initially presumed to be because of the diagnosis of gastroschisis and the prolonged use of parenteral nutrition. However, both infants were eventually found to have an associated choledochal cyst. The cases are a novel association not previously reported and should heighten the awareness that anatomical causes of a direct hyperbilirubinemia need to be ruled out in all neonates.

Effects of endotoxin and catecholamines on hepatic mitochondrial respiration

Catecholamines are frequently used in sepsis, but their interaction with mitochondrial function is controversial. We incubated isolated native and endotoxin-exposed swine liver mitochondria with either dopamine, dobutamine, noradrenaline or placebo for 1 h. Mitochondrial State 3 and 4 respiration and their ratio (RCR) were determined for respiratory chain complexes I, II and IV. All catecholamines impaired glutamate-dependent RCR (p = 0.046), predominantly in native mitochondria. Endotoxin incubation alone induced a decrease in glutamate-dependent RCR compared to control samples (p = 0.002). We conclude that catecholamines and endotoxin impair the efficiency of mitochondrial complex I respiration in vitro.

Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease

The efficacy of mammalian target of rapamycin (mTOR) inhibitors is currently tested in patients affected by autosomal dominant polycystic kidney disease. Treatment with mTOR inhibitors has been associated with numerous side effects. However, the renal-specific effect of mTOR inhibitor treatment cessation in polycystic kidney disease is currently unknown. Therefore, we compared pulse and continuous everolimus treatment in Han:SPRD rats. Four-week-old male heterozygous polycystic and wild-type rats were administered everolimus or vehicle by gavage feeding for 5 wk, followed by 7 wk without treatment, or continuously for 12 wk. Cessation of everolimus did not result in the appearance of renal cysts up to 7 wk postwithdrawal despite the reemergence of S6 kinase activity coupled with an overall increase in cell proliferation. Pulse everolimus treatment resulted in striking noncystic renal parenchymal enlargement and glomerular hypertrophy that was not associated with compromised kidney function. Both treatment regimens ameliorated kidney function, preserved the glomerular-tubular connection, and reduced proteinuria. Pulse treatment at an early age delays cyst development but leads to striking glomerular and parenchymal hypertrophy. Our data might have an impact when long-term treatment using mTOR inhibitors in patients with autosomal dominant polycystic kidney disease is being considered.

Long-term quality of life after hepatic resection: health is not simply the absence of disease

BACKGROUND: Due to advances in operative methods and perioperative care, mortality and morbidity following major hepatic resection have decreased substantially, making long-term quality of life (QoL) an increasingly prominent issue. We evaluated whether postoperative diagnosis was associated with long-term QoL and health in patients requiring hepatic surgery for benign or malignant disease. METHODS: QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the liver-specific QLQ-LMC21 module. RESULTS: Between 2002 and 2006, 249 patients underwent hepatic surgery for malignant (76%) and benign (24%) conditions. One hundred thirty-five patients were available for QoL analysis after a mean of 26.5 months. There was no statistical difference in global QoL scores between patients with malignant and benign diseases (p = 0.367). Neither the extent of the resection (> or =2 segments vs. <2 segments; p = 0.975; OR = 0.988; 95% CI = 0.461-2.119) nor patient age had a significant influence on overall QoL (p = 0.092). CONCLUSIONS: These results indicate that long-term QoL for patients who underwent liver resection for malignant disease is quite good and that a poor clinical prognosis does not seem to correlate with a poor QoL.

Symptomatic retroperitoneal cyst: a diagnostic challenge

Retroperitoneal cystic masses pose an important diagnostic and therapeutic challenge. Simple drainage, internal or external, is usually not sufficient. We report a case of a large symptomatic retroperitoneal cyst and its management.

Concomitant injuries are an important determinant of outcome of high-grade blunt hepatic trauma

BACKGROUND: Little is known about the clinical importance of concomitant injuries in polytraumatized patients with high-grade blunt liver injury. A retrospective single-centre study was performed to investigate the safety of non-operative management of liver injury and the impact of concomitant intra- and extra-abdominal injuries on clinical outcome. METHODS: Some 183 patients with blunt liver injury were admitted to Berne University Hospital, Switzerland, between January 2000 and December 2006. Grade 3-5 injuries were considered to be high grade. RESULTS: Immediate laparotomy was required by 35 patients (19.1 per cent), owing to extrahepatic intra-abdominal injury (splenic and vascular injuries, perforations) in 21 cases. The mortality rate was 16.9 per cent; 22 of the 31 deaths were due to concomitant lesions. Of 81 patients with high-grade liver injury, 63 (78 per cent) were managed without surgery; liver-related and extra-abdominal complication rates in these patients were 11 and 17 per cent respectively. Grades 4 and 5 liver injury were associated with hepatic-related and extra-abdominal complications. CONCLUSION: Concomitant injuries are a major determinant of outcome in patients with blunt hepatic injury and should be given high priority by trauma surgeons. An algorithm for the management of blunt liver injury is proposed.

Differential diagnosis of CT focal liver lesions using texture features, feature selection and ensemble driven classifiers

The aim of the present study is to define an optimally performing computer-aided diagnosis (CAD) architecture for the classification of liver tissue from non-enhanced computed tomography (CT) images into normal liver (C1), hepatic cyst (C2), hemangioma (C3), and hepatocellular carcinoma (C4). To this end, various CAD architectures, based on texture features and ensembles of classifiers (ECs), are comparatively assessed.

A computer-aided diagnostic system to characterize CT focal liver lesions: design and optimization of a neural network classifier

In this paper, a computer-aided diagnostic (CAD) system for the classification of hepatic lesions from computed tomography (CT) images is presented. Regions of interest (ROIs) taken from nonenhanced CT images of normal liver, hepatic cysts, hemangiomas, and hepatocellular carcinomas have been used as input to the system. The proposed system consists of two modules: the feature extraction and the classification modules. The feature extraction module calculates the average gray level and 48 texture characteristics, which are derived from the spatial gray-level co-occurrence matrices, obtained from the ROIs. The classifier module consists of three sequentially placed feed-forward neural networks (NNs). The first NN classifies into normal or pathological liver regions. The pathological liver regions are characterized by the second NN as cyst or "other disease." The third NN classifies "other disease" into hemangioma or hepatocellular carcinoma. Three feature selection techniques have been applied to each individual NN: the sequential forward selection, the sequential floating forward selection, and a genetic algorithm for feature selection. The comparative study of the above dimensionality reduction methods shows that genetic algorithms result in lower dimension feature vectors and improved classification performance.