Efficacy of a non-invasive model in predicting the cardiovascular morbidity and histological severity in non-alcoholic fatty liver disease

BackgroundInsulin resistance (IR) in cases of non-alcoholic fatty liver disease (NAFLD) is connected to remarkable liver cell inflammation and cardiovascular complications. Given the prevalence of NAFLD and its association with potential sequels, there is a strong need for an accurate non-invasive tool to monitor the progression of NAFLD.Methods272 patients with NAFLD and cardio-metabolic risk factors were tested for HOMA-IR, mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), uric acid, ferritin, lipid profile, liver stiffness measurement (LSM), controlled attenuation parameter (CAP) by fibroscan and carotid intima media thickness (CIMT). Liver biopsy was performed to validate the results.100 healthy controls were selected. A score was constructed and applied to a validation group (n = 61).ResultsLogistic regression revealed that significant fibrosis and cardiovascular risk in NAFLD were independently associated with AST/ALT ratio (p = 0.000), GGT (p = 0.000), CIMT (p = 0.001), uric acid (p = 0.000), VLDL (p = 0.000), HOMA-IR (p = 0.000), ferritin (p = 0.000) CAP (p = 0.000), LSM (p0.000). A non-invasive model was formulated by which a value > 15 was accurate in identification of advanced fibrosis and cardiovascular risk with a sensitivity of 97.3%, specificity 97%.ConclusionThe score correlated well with the results of liver biopsy and can be repeated with great flexibility to assess severity of NAFLD.     

Imaging of Fibrogenesis in Patients with Idiopathic Pulmonary Fibrosis with cis-4-[18F]-Fluoro-l-Proline PET

Purpose  Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which no single diagnostic modality is able to evaluate the activity of the disease process. Cis-4-¹⁸F-fluoro-l-proline (¹⁸F-proline) was shown in animal studies to be a reliable marker for fibrosis formation. We tested this candidate radioligand for imaging of fibrogenesis in patients with IPF. Methods  Five patients with IPF proven by lung biopsy and computed tomography were included. Furthermore, we also included one patient with non-specific interstitial pneumonia (NSIP) and scleroderma and one with NSIP and organising pneumonia. Positron emission tomography (PET) acquisition was performed 1, 2 and 3h after injection of 400MBq ¹⁸F-proline. We scored ¹⁸F-proline activity visually and quantitatively by calculating the activity in the regions of interest over lung, liver and mediastinum. Results  We found low uptake of ¹⁸F-proline in the lungs of all patients with IPF. The highest uptake was seen at 2h post-injection, with a decline at 3h past injection. The differences in lung uptake between patients were small, except for one patient with NSIP and organising pneumonia who had a slightly higher ¹⁸F-proline uptake. No significant correlations between ¹⁸F-proline uptake and clinical parameters were found. Conclusions  Due to the low pulmonary uptake of ¹⁸F-proline in patients with IPF, ¹⁸F-proline does not seem to be a suitable radioligand to evaluate the activity of fibrosis formation in patients with IPF. The low uptake in the lungs of patients with interstitial fibrosis may be explained by the slow nature of fibrogenesis or to the relatively low dose of proline that can be used.     

Changes of shear-wave velocity by interferon-based therapy in chronic hepatitis C

AIM: To evaluate the changes of shear-wave velocity(Vs) by acoustic radiation force impulse after treatment in chronic hepatitis C.METHODS: Eighty-seven patients with chronic hepatitis C were consecutively treated with combinations of interferon(IFN) plus ribavirin(RBV). Vs value(m/s) was measured with acoustic radiation force impulse before treatment, at end of treatment(EOT), 1 year after EOT, and 2 years after EOT.RESULTS: In patients with a sustained virological response(SVR)(n = 41), Vs significantly decreased at EOT [1.19(1.07-1.37), P = 0.0004], 1 year after EOT [1.10(1.00-1.22), P = 0.0001], and 2 years after EOT [1.05(0.95-1.16), P 0.0001] compared with baseline [1.27(1.11-1.49)]. In patients with a relapse(n = 26), Vs did not significantly decrease at EOT [1.23(1.12-1.55)], 1 year after EOT [1.20(1.12-1.80)], and 2 years after EOT [1.41(1.08-2.01)] compared with baseline [1.39(1.15-1.57)]. In patients with a nonvirological response(n = 20), Vs did not significantly decrease at EOT [1.64(1.43-2.06)], 1 year after EOT [1.66(1.30-1.95)], and 2 years after EOT [1.61(1.36-2.37)] compared with baseline [1.80(1.54-2.01)]. Among genotype 1 patients, baseline Vs was significantly lower in SVR patients [1.28(1.04-1.40)] than in non-SVR patients [1.56(1.20-1.83)](P = 0.0142).CONCLUSION: Reduction of Vs values was shown in SVR patients after IFN-plus-RBV therapy by acoustic radiation force impulse.     

Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: Pathology and beyond

Non-alcoholic steatohepatitis(NASH) is considered to be the hepatic manifestation of the metabolic syndrome, thus has a tight correlation with systemic metabolic impairment. The complex mechanisms underlying the pathogenesis of NASH involve different organs and systems that cross talk together contributing to the onset of NASH. A crucial role is played by inflammatory mediators, especially those deriving from the adipose tissue and the liver, which are involved in the cascade of inflammation, fibrosis and eventually tumorigenesis. In this setting cytokines and adipokines as well as immunity are emerging drivers of the key features of NASH. The immune system participates in this process with disturbances of the cells constituting both the innate and the adaptive immune systems that have been reported in different organs, such as in the liver and in the adipose tissue, in clinical and preclinical studies. The role of the immune system in NASH is increasingly studied, not only because of its contribution to the pathogenetic mechanisms of NASH but also because of the new potential therapeutic options it offers in this setting. Indeed, novel treatments acting on the immune system could offer new options in the management of NASH and the correlated clinical consequences.     

白藜芦醇对小鼠慢性病毒性心肌炎心肌纤维化的干预作用

目的：目前研究认为白藜芦醇能改善病毒性心肌炎(VMC)急性期小鼠心功能及心肌损伤,在体外也具有抑制小鼠心肌纤维化的作用,但在VMC慢性期小鼠模型上,是否具有抑制心肌纤维化的作用尚未见报道。该研究旨在探讨白藜芦醇对VMC慢性期心肌纤维化干预的效果,从而为临床治疗VMC提供一定的实验依据。方法：柯萨奇病毒B3(CVB3)感染BALA/c小鼠建立VMC慢性期动物模型,30 d后将小鼠随机分为VMC模型对照组, 白藜芦醇小剂量组(10 mg/kg),中剂量组(100 mg/kg)及大剂量组(1 000 mg/kg),并设正常对照。30 d后,处死小鼠摘取心脏及提取血液,酶联免疫吸附法测各组小鼠胶原前肽(PINP,PICP及PIIINP)的血清浓度,心脏切片行苏木精-伊红染色及苦味酸天狼猩红胶原组织化学染色并计算胶原容积积分。结果：白藜芦醇大剂量组（0.74±0.19）及中剂量组（1.07±0.12）心肌胶原容积积分较小剂量组(2.17±0.19)和VMC模型对照组(2.33±0.18)明显减少,差异有显著性(P<0.05)。 大剂量组和中剂量组比较差异无显著性,小剂量组和VMC模型对照组比较差异无显著性。与VMC模型对照组比较,白藜芦醇高剂量组及中剂量组血清中Ⅰ型前胶原羧基端前肽（PICP）及Ⅲ型前胶原氨基端前肽（PIIICP）含量明显减少,差异有显著性（P<0.05）,而Ⅰ型前胶原氨基端前肽（PINP）含量明显增多,差异亦有显著性（P<0.05）。结论：VMC慢性期小鼠模型上,白藜芦醇能抑制VMC心肌胶原的增生,具有抗心肌纤维化的作用。［中国当代儿科杂志,2009,11（4）：291-295］     

A soluble factor (EMMPRIN) in exudate influences knee motion after total arthroplasty

Few studies have been conducted to investigate biological factors that affect postoperative knee motion after total knee arthroplasty (TKA). The purpose of this study is to test the hypothesis that range of knee motion (ROM) at 4 weeks after TKA is correlated with the concentration of extracellular matrix metalloproteinase inducer (EMMPRIN) and transforming growth factor (TGF)-beta1 in the exudative fluid harvested from the joint after surgery. A prospective measurement study was conducted with 20 osteoarthritis patients who underwent TKA. At 48 h after surgery, the exudate was harvested from a closed drainage system. Enzyme-linked immunosorbent assay was performed to measure the concentration of TGF-beta1, EMMPRIN, MMP-1, 2, 9, tissue inhibitor of metalloproteinase-1, and Hyalunonan. Knee flexion angle was measured before and at 4 weeks after surgery. There was a significant correlation between the EMMPRIN levels and knee flexion angle (r = 0.557, p = 0.0148). Western blot analysis of the exudate showed a prominent band for EMMPRIN at 27 kDa. On the other hand, there was no correlation between the TGF-beta1 levels and the knee flexion angle. This study showed that EMMPRIN levels after TKA affect the postoperative ROM. As to clinical relevance, EMMPRIN in the exudate after TKA is a promising biological indicator to predict difficulty in restoring postoperative ROM.     

Mesenteric panniculitis： Various presentations and treatment regimens

Mesenteric panniculitis is a rare, benign and chronic fibrosing inflammatory disease that affects the adipose tissue of the mesentery of the small intestine and colon. The specific etiology of the disease is unknown. The diagnosis is suggested by computed tomography and is usually confirmed by surgical biopsies. Treatment is empirical and based on a few selected drugs. Surgical resection is sometimes attempted for definitive therapy, although the surgical approach is often limited. We report two cases of mesenteric panniculitis with two different presentations and subsequently varying treatment regimens. Adequate response was obtained in both patients. We present details of these cases as well as a literature review to compare various presentations, etiologies and potential treatment modalities.